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Atas, Heval; Joshi, Vishal; Atakan, Ahmet; Rifaioglu, Ahmet Sureyya; Nalbat, Esra; Nightingale, Andrew; Saidi, Rabie; Volynkin, Vladimir; Zellner, Hermann; Cetin-Atalay, Rengul; Martin, Maria; Atalay, Volkan title: CROssBAR: Comprehensive Resource of Biomedical Relations with Deep Learning Applications and Knowledge Graph Representations date: 2020-09-15 journal: bioRxiv DOI: 10.1101/2020.09.14.296889 sha: doc_id: 350935 cord_uid: p6euuop3 file: cache/cord-339091-3xk2w0d2.json key: cord-339091-3xk2w0d2 authors: Flower, Darren R; Macdonald, Isabel K; Ramakrishnan, Kamna; Davies, Matthew N; Doytchinova, Irini A title: Computer aided selection of candidate vaccine antigens date: 2010-11-03 journal: Immunome Res DOI: 10.1186/1745-7580-6-s2-s1 sha: doc_id: 339091 cord_uid: 3xk2w0d2 file: cache/cord-355327-d3gcfepx.json key: cord-355327-d3gcfepx authors: Fan, Samuel W; George, Richard A; Haworth, Naomi L; Feng, Lina L; Liu, Jason Y; Wouters, Merridee A title: Conformational changes in redox pairs of protein structures date: 2009-08-01 journal: Protein Science DOI: 10.1002/pro.175 sha: doc_id: 355327 cord_uid: d3gcfepx file: cache/cord-342118-fsmuqktd.json key: cord-342118-fsmuqktd authors: Dyakov, Ilya N.; Mavletova, Dilara A.; Chernyshova, Irina N.; Snegireva, Nadezda A.; Gavrilova, Marina V.; Bushkova, Kristina K.; Dyachkova, Marina S.; Alekseeva, Maria G.; Danilenko, Valery N. title: FN3 protein fragment containing two type III fibronectin domains from B. longum GT15 binds to human tumor necrosis factor alpha in vitro date: 2020-08-06 journal: Anaerobe DOI: 10.1016/j.anaerobe.2020.102247 sha: doc_id: 342118 cord_uid: fsmuqktd file: cache/cord-343791-0vykwml5.json key: cord-343791-0vykwml5 authors: Hainline, Kelly M.; Fries, Chelsea N.; Collier, Joel H. title: Progress towards the clinical translation of bio-inspired peptide and protein assemblies date: 2017-11-08 journal: Advanced Healthcare Materials DOI: 10.1002/adhm.201700930 sha: doc_id: 343791 cord_uid: 0vykwml5 file: cache/cord-352172-g0jiaenw.json key: cord-352172-g0jiaenw authors: Stoevesandt, Oda; Taussig, Michael J; He, Mingyue title: Protein microarrays: high-throughput tools for proteomics date: 2014-01-09 journal: Expert Rev Proteomics DOI: 10.1586/epr.09.2 sha: doc_id: 352172 cord_uid: g0jiaenw file: cache/cord-355913-fhvt1ht1.json key: cord-355913-fhvt1ht1 authors: Burrell, Christopher J.; Howard, Colin R.; Murphy, Frederick A. title: Virus Replication date: 2016-11-11 journal: Fenner and White's Medical Virology DOI: 10.1016/b978-0-12-375156-0.00004-7 sha: doc_id: 355913 cord_uid: fhvt1ht1 file: cache/cord-337158-0iw2kcaf.json key: cord-337158-0iw2kcaf authors: Tiernan, Hannah; Byrne, Bernadette; Kazarian, Sergei G. title: ATR-FTIR spectroscopy and spectroscopic imaging for the analysis of biopharmaceuticals date: 2020-06-22 journal: Spectrochim Acta A Mol Biomol Spectrosc DOI: 10.1016/j.saa.2020.118636 sha: doc_id: 337158 cord_uid: 0iw2kcaf file: cache/cord-341564-fvuwick5.json key: cord-341564-fvuwick5 authors: Qi, Zhao-Hui; Li, Ke-Cheng; Ma, Jin-Long; Yao, Yu-Hua; Liu, Ling-Yun title: Novel Method of 3-Dimensional Graphical Representation for Proteins and Its Application date: 2018-06-12 journal: Evol Bioinform Online DOI: 10.1177/1176934318777755 sha: doc_id: 341564 cord_uid: fvuwick5 file: cache/cord-355477-7xd93aqv.json key: cord-355477-7xd93aqv authors: SATIJA, NAMITA; LAL, SUNIL K. title: The Molecular Biology of SARS Coronavirus date: 2007-04-23 journal: Ann N Y Acad Sci DOI: 10.1196/annals.1408.002 sha: doc_id: 355477 cord_uid: 7xd93aqv file: cache/cord-347714-vxxhglx7.json key: cord-347714-vxxhglx7 authors: Abitogun, Folagbade; Srivastava, R.; Sharma, S.; Komarysta, V.; Akurut, E.; Munir, N.; Macalalad, L.; Olawale, O.; Owolabi, O.; Abayomi, G.; Debnath, S. title: COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding date: 2020-10-14 journal: bioRxiv DOI: 10.1101/2020.10.14.339689 sha: doc_id: 347714 cord_uid: vxxhglx7 file: cache/cord-349774-898tmq14.json key: cord-349774-898tmq14 authors: Zhang, Haiyang; Tu, Jialu; Cao, Chulei; Yang, Ting; Gao, Liangcai title: Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein date: 2020-06-16 journal: Biochem Biophys Res Commun DOI: 10.1016/j.bbrc.2020.06.058 sha: doc_id: 349774 cord_uid: 898tmq14 file: cache/cord-346314-o9fjpqaj.json key: cord-346314-o9fjpqaj authors: Jarboui, Mohamed Ali; Bidoia, Carlo; Woods, Elena; Roe, Barbara; Wynne, Kieran; Elia, Giuliano; Hall, William W.; Gautier, Virginie W. title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus date: 2012-11-15 journal: PLoS One DOI: 10.1371/journal.pone.0048702 sha: doc_id: 346314 cord_uid: o9fjpqaj file: cache/cord-345712-gmzue6lj.json key: cord-345712-gmzue6lj authors: Palazzo, Luca; Mikoč, Andreja; Ahel, Ivan title: ADP‐ribosylation: new facets of an ancient modification date: 2017-04-26 journal: FEBS J DOI: 10.1111/febs.14078 sha: doc_id: 345712 cord_uid: gmzue6lj file: cache/cord-341701-zropd3mo.json key: cord-341701-zropd3mo authors: Adhikari, Subash; Nice, Edouard C.; Deutsch, Eric W.; Lane, Lydie; Omenn, Gilbert S.; Pennington, Stephen R.; Paik, Young-Ki; Overall, Christopher M.; Corrales, Fernando J.; Cristea, Ileana M.; Van Eyk, Jennifer E.; Uhlén, Mathias; Lindskog, Cecilia; Chan, Daniel W.; Bairoch, Amos; Waddington, James C.; Justice, Joshua L.; LaBaer, Joshua; Rodriguez, Henry; He, Fuchu; Kostrzewa, Markus; Ping, Peipei; Gundry, Rebekah L.; Stewart, Peter; Srivastava, Sanjeeva; Srivastava, Sudhir; Nogueira, Fabio C. S.; Domont, Gilberto B.; Vandenbrouck, Yves; Lam, Maggie P. Y.; Wennersten, Sara; Vizcaino, Juan Antonio; Wilkins, Marc; Schwenk, Jochen M.; Lundberg, Emma; Bandeira, Nuno; Marko-Varga, Gyorgy; Weintraub, Susan T.; Pineau, Charles; Kusebauch, Ulrike; Moritz, Robert L.; Ahn, Seong Beom; Palmblad, Magnus; Snyder, Michael P.; Aebersold, Ruedi; Baker, Mark S. title: A high-stringency blueprint of the human proteome date: 2020-10-16 journal: Nat Commun DOI: 10.1038/s41467-020-19045-9 sha: doc_id: 341701 cord_uid: zropd3mo file: cache/cord-347661-q9lgliph.json key: cord-347661-q9lgliph authors: Zevenhoven-Dobbe, Jessika C.; Wassenaar, Alfred L. M.; van der Meer, Yvonne; Snijder, Eric J. title: Production of Monospecific Rabbit Antisera Recognizing Nidovirus Proteins date: 2007-11-28 journal: SARS- and Other Coronaviruses DOI: 10.1007/978-1-59745-181-9_16 sha: doc_id: 347661 cord_uid: q9lgliph file: cache/cord-342756-rgm9ffpk.json key: cord-342756-rgm9ffpk authors: Senger, Mario Roberto; Evangelista, Tereza Cristina Santos; Dantas, Rafael Ferreira; Santana, Marcos Vinicius da Silva; Gonçalves, Luiz Carlos Saramago; de Souza Neto, Lauro Ribeiro; Ferreira, Sabrina Baptista; Silva-Junior, Floriano Paes title: COVID-19: molecular targets, drug repurposing and new avenues for drug discovery date: 2020-10-02 journal: Mem Inst Oswaldo Cruz DOI: 10.1590/0074-02760200254 sha: doc_id: 342756 cord_uid: rgm9ffpk file: cache/cord-354030-8tfg881h.json key: cord-354030-8tfg881h authors: Dong, Rong; Chu, Zhugang; Yu, Fuxun; Zha, Yan title: Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches date: 2020-07-28 journal: Front Immunol DOI: 10.3389/fimmu.2020.01784 sha: doc_id: 354030 cord_uid: 8tfg881h file: cache/cord-346965-0oq2n0af.json key: cord-346965-0oq2n0af authors: Liu, Zhi-Ping; Wu, Ling-Yun; Wang, Yong; Zhang, Xiang-Sun; Chen, Luonan title: Bridging protein local structures and protein functions date: 2008-04-18 journal: Amino Acids DOI: 10.1007/s00726-008-0088-8 sha: doc_id: 346965 cord_uid: 0oq2n0af file: cache/cord-352481-iq3wor3w.json key: cord-352481-iq3wor3w authors: Postic, Guillaume; Janel, Nathalie; Tufféry, Pierre; Moroy, Gautier title: An information gain-based approach for evaluating protein structure models date: 2020-08-18 journal: Comput Struct Biotechnol J DOI: 10.1016/j.csbj.2020.08.013 sha: doc_id: 352481 cord_uid: iq3wor3w file: cache/cord-356064-q56jnhss.json key: cord-356064-q56jnhss authors: Bartel, Sebastian; Doellinger, Joerg; Darsow, Kai; Bourquain, Daniel; Buchholz, Rainer; Nitsche, Andreas; Lange, Harald A title: Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides date: 2011-08-01 journal: Virol J DOI: 10.1186/1743-422x-8-380 sha: doc_id: 356064 cord_uid: q56jnhss file: cache/cord-346916-jj4l9ydl.json key: cord-346916-jj4l9ydl authors: Girardi, Erika; Pfeffer, Sebastien; Baumert, Thomas F.; Majzoub, Karim title: Roadblocks and fast tracks: How RNA binding proteins affect the viral RNA journey in the cell date: 2020-08-23 journal: Semin Cell Dev Biol DOI: 10.1016/j.semcdb.2020.08.006 sha: doc_id: 346916 cord_uid: jj4l9ydl file: cache/cord-355924-8sk9al0n.json key: cord-355924-8sk9al0n authors: Allam, Loubna; Ghrifi, Fatima; Mohammed, Hakmi; El Hafidi, Naima; El Jaoudi, Rachid; El Harti, Jaouad; Lmimouni, Badreddine; Belyamani, Lahcen; Ibrahimi, Azeddine title: Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules date: 2020-10-21 journal: Bioinform Biol Insights DOI: 10.1177/1177932220965505 sha: doc_id: 355924 cord_uid: 8sk9al0n file: cache/cord-348972-r94fhpe0.json key: cord-348972-r94fhpe0 authors: Gussow, Ayal B.; Park, Allyson E.; Borges, Adair L.; Shmakov, Sergey A.; Makarova, Kira S.; Wolf, Yuri I.; Bondy-Denomy, Joseph; Koonin, Eugene V. title: Machine-learning approach expands the repertoire of anti-CRISPR protein families date: 2020-07-29 journal: Nat Commun DOI: 10.1038/s41467-020-17652-0 sha: doc_id: 348972 cord_uid: r94fhpe0 file: cache/cord-351559-az4pgi9k.json key: cord-351559-az4pgi9k authors: Turjya, Rafeed Rahman; Khan, Md. Abdullah-Al-Kamran; Islam, Abul Bashar Mir Md. Khademul title: Perversely expressed long noncoding RNAs can alter host response and viral proliferation in SARS-CoV-2 infection date: 2020-06-29 journal: bioRxiv DOI: 10.1101/2020.06.29.177204 sha: doc_id: 351559 cord_uid: az4pgi9k file: cache/cord-355377-b0rcg3rt.json key: cord-355377-b0rcg3rt authors: van der Vlag, R.; Hirsch, A.K.H. title: Analytical Methods in Protein-Templated Dynamic Combinatorial Chemistry date: 2017-06-29 journal: Comprehensive Supramolecular Chemistry II DOI: 10.1016/b978-0-12-409547-2.12559-4 sha: doc_id: 355377 cord_uid: b0rcg3rt file: cache/cord-354547-eomm1sl5.json key: cord-354547-eomm1sl5 authors: Wang, Jibin; Fang, Shouguo; Xiao, Han; Chen, Bo; Tam, James P.; Liu, Ding Xiang title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding date: 2009-03-16 journal: PLoS One DOI: 10.1371/journal.pone.0004908 sha: doc_id: 354547 cord_uid: eomm1sl5 file: cache/cord-354950-kmpbdvof.json key: cord-354950-kmpbdvof authors: Demurtas, Olivia C.; Massa, Silvia; Illiano, Elena; De Martinis, Domenico; Chan, Paul K. S.; Di Bonito, Paola; Franconi, Rosella title: Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS date: 2016-02-05 journal: Front Plant Sci DOI: 10.3389/fpls.2016.00054 sha: doc_id: 354950 cord_uid: kmpbdvof file: cache/cord-347710-ff64y6ef.json key: cord-347710-ff64y6ef authors: Wan, Qianya; Song, Dan; Li, Huangcan; He, Ming-liang title: Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date: 2020-07-13 journal: Signal Transduct Target Ther DOI: 10.1038/s41392-020-00233-4 sha: doc_id: 347710 cord_uid: ff64y6ef Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-protein-cord === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 11451 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 13623 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 11428 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 13395 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 13921 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 13937 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 12087 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 12510 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 14233 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 11359 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 13504 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 13922 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 14161 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 14289 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 14357 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 14931 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 17014 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 14785 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 15442 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 17138 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 18556 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 18852 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 17184 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 19488 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 15151 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 16293 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 17842 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 17353 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 18771 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 18843 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 20933 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 17084 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 17087 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 18365 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 15608 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 17051 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 15028 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 20310 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 20616 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 84. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 14671 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 11986 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 16879 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 17435 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 19755 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 19853 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 20016 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 20976 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-000575-g1ob16b9 author: Xie, Xiao-li title: Protein sequence analysis based on hydropathy profile of amino acids date: 2012-01-27 pages: extension: .txt txt: ./txt/cord-000575-g1ob16b9.txt cache: ./cache/cord-000575-g1ob16b9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-000575-g1ob16b9.txt' /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-000708-iuo2cw23 author: Lippé, Roger title: Deciphering Novel Host–Herpesvirus Interactions by Virion Proteomics date: 2012-05-28 pages: extension: .txt txt: ./txt/cord-000708-iuo2cw23.txt cache: ./cache/cord-000708-iuo2cw23.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-000708-iuo2cw23.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 22919 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-009959-erh8ggh3 author: BENTLEY, WILLIAM E. title: Development of an Efficient Bioprocess for Poultry Vaccines Using High‐density Insect Cell Culture date: 2006-12-17 pages: extension: .txt txt: ./txt/cord-009959-erh8ggh3.txt cache: ./cache/cord-009959-erh8ggh3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-009959-erh8ggh3.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-002973-bkr4ndl2 author: Seifi, Morteza title: Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms date: 2018-04-17 pages: extension: .txt txt: ./txt/cord-002973-bkr4ndl2.txt cache: ./cache/cord-002973-bkr4ndl2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002973-bkr4ndl2.txt' /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-013046-r6dtiu97 author: Liu, Bin title: Combining evolutionary information extracted from frequency profiles with sequence-based kernels for protein remote homology detection date: 2014-02-15 pages: extension: .txt txt: ./txt/cord-013046-r6dtiu97.txt cache: ./cache/cord-013046-r6dtiu97.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-013046-r6dtiu97.txt' === file2bib.sh === id: cord-001244-qdld7hdc author: Fan, Yue-Nong title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking date: 2014-03-19 pages: extension: .txt txt: ./txt/cord-001244-qdld7hdc.txt cache: ./cache/cord-001244-qdld7hdc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001244-qdld7hdc.txt' === file2bib.sh === id: cord-002100-dt5zvebj author: He, Yonghua title: Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF) date: 2016-06-17 pages: extension: .txt txt: ./txt/cord-002100-dt5zvebj.txt cache: ./cache/cord-002100-dt5zvebj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002100-dt5zvebj.txt' === file2bib.sh === id: cord-001898-ntqyjqqk author: Huang, Chih-Wei title: Lys-315 at the Interfaces of Diagonal Subunits of δ-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly date: 2016-01-05 pages: extension: .txt txt: ./txt/cord-001898-ntqyjqqk.txt cache: ./cache/cord-001898-ntqyjqqk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-001898-ntqyjqqk.txt' === file2bib.sh === id: cord-004673-c8qcjve9 author: Faaberg, K. S. title: Membrane association of the C-terminal half of the open reading frame 1a protein of lactate dehydrogenase-elevating virus date: 1996 pages: extension: .txt txt: ./txt/cord-004673-c8qcjve9.txt cache: ./cache/cord-004673-c8qcjve9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004673-c8qcjve9.txt' === file2bib.sh === id: cord-000182-ni6iyzdn author: He, Zhisong title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features date: 2010-03-11 pages: extension: .txt txt: ./txt/cord-000182-ni6iyzdn.txt cache: ./cache/cord-000182-ni6iyzdn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000182-ni6iyzdn.txt' === file2bib.sh === id: cord-004719-3stcx0dd author: Mushegian, A. R. title: Cell-to-cell movement of plant viruses: Insights from amino acid sequence comparisons of movement proteins and from analogies with cellular transport systems date: 1993 pages: extension: .txt txt: ./txt/cord-004719-3stcx0dd.txt cache: ./cache/cord-004719-3stcx0dd.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-004719-3stcx0dd.txt' === file2bib.sh === id: cord-005145-1l87fdmi author: Marquet-Blouin, E. title: Neutralizing immunogenicity of transgenic carrot (Daucus carota L.)-derived measles virus hemagglutinin date: 2003 pages: extension: .txt txt: ./txt/cord-005145-1l87fdmi.txt cache: ./cache/cord-005145-1l87fdmi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-005145-1l87fdmi.txt' === file2bib.sh === id: cord-000642-mkwpuav6 author: Moreira, Rebeca title: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing date: 2012-04-19 pages: extension: .txt txt: ./txt/cord-000642-mkwpuav6.txt cache: ./cache/cord-000642-mkwpuav6.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-000642-mkwpuav6.txt' === file2bib.sh === id: cord-002739-7t1o19kn author: Yu, Xiaobo title: Multiplexed Nucleic Acid Programmable Protein Arrays date: 2017-09-20 pages: extension: .txt txt: ./txt/cord-002739-7t1o19kn.txt cache: ./cache/cord-002739-7t1o19kn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002739-7t1o19kn.txt' === file2bib.sh === id: cord-003144-nqkw5v3w author: Qu, Zehui title: Label‐Free Quantitative Proteomic Analysis of Differentially Expressed Membrane Proteins of Pulmonary Alveolar Macrophages Infected with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Its Attenuated Strain date: 2017-11-24 pages: extension: .txt txt: ./txt/cord-003144-nqkw5v3w.txt cache: ./cache/cord-003144-nqkw5v3w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003144-nqkw5v3w.txt' === file2bib.sh === id: cord-012682-7goljir4 author: Yuan, Meng title: N-myristoylation: from cell biology to translational medicine date: 2020-03-18 pages: extension: .txt txt: ./txt/cord-012682-7goljir4.txt cache: ./cache/cord-012682-7goljir4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-012682-7goljir4.txt' === file2bib.sh === id: cord-000003-ejv2xln0 author: Crouch, Erika C title: Surfactant protein-D and pulmonary host defense date: 2000-08-25 pages: extension: .txt txt: ./txt/cord-000003-ejv2xln0.txt cache: ./cache/cord-000003-ejv2xln0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-000003-ejv2xln0.txt' === file2bib.sh === id: cord-003761-ikni2acz author: Li, Zengbin title: Biological Function and Application of Picornaviral 2B Protein: A New Target for Antiviral Drug Development date: 2019-06-04 pages: extension: .txt txt: ./txt/cord-003761-ikni2acz.txt cache: ./cache/cord-003761-ikni2acz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003761-ikni2acz.txt' === file2bib.sh === id: cord-000479-u87eaaj8 author: Stolf, Beatriz S. title: Protein Disulfide Isomerase and Host-Pathogen Interaction date: 2011-10-11 pages: extension: .txt txt: ./txt/cord-000479-u87eaaj8.txt cache: ./cache/cord-000479-u87eaaj8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000479-u87eaaj8.txt' === file2bib.sh === id: cord-001435-ebl8yc92 author: Hoppe, Sebastian title: Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae date: 2014-10-21 pages: extension: .txt txt: ./txt/cord-001435-ebl8yc92.txt cache: ./cache/cord-001435-ebl8yc92.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-001435-ebl8yc92.txt' === file2bib.sh === id: cord-010938-12igesqw author: Patra, Prasanta title: Epitope-Based Vaccine Designing of Nocardia asteroides Targeting the Virulence Factor Mce-Family Protein by Immunoinformatics Approach date: 2019-08-21 pages: extension: .txt txt: ./txt/cord-010938-12igesqw.txt cache: ./cache/cord-010938-12igesqw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-010938-12igesqw.txt' === file2bib.sh === id: cord-003297-fewy8y4a author: Wang, Ming-Yang title: A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs date: 2018-09-18 pages: extension: .txt txt: ./txt/cord-003297-fewy8y4a.txt cache: ./cache/cord-003297-fewy8y4a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003297-fewy8y4a.txt' === file2bib.sh === id: cord-014368-4nasrbs6 author: nan title: Gene Chip for Viral Discovery date: 2003-11-17 pages: extension: .txt txt: ./txt/cord-014368-4nasrbs6.txt cache: ./cache/cord-014368-4nasrbs6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-014368-4nasrbs6.txt' === file2bib.sh === id: cord-018493-q24f86e9 author: Ranjan, Prabhat title: Importance of Natural Proteins in Infectious Diseases date: 2015-08-08 pages: extension: .txt txt: ./txt/cord-018493-q24f86e9.txt cache: ./cache/cord-018493-q24f86e9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018493-q24f86e9.txt' === file2bib.sh === id: cord-018479-mvnm98hv author: Rehm, Fabian B. H. title: Applications of Microbial Biopolymers in Display Technology date: 2017-11-16 pages: extension: .txt txt: ./txt/cord-018479-mvnm98hv.txt cache: ./cache/cord-018479-mvnm98hv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-018479-mvnm98hv.txt' === file2bib.sh === id: cord-020097-eh5deunk author: nan title: Cumulative Author Index for 2006 (Volumes 115–122) date: 2006-10-27 pages: extension: .txt txt: ./txt/cord-020097-eh5deunk.txt cache: ./cache/cord-020097-eh5deunk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-020097-eh5deunk.txt' === file2bib.sh === id: cord-022200-hqc8r31t author: HYATT, ALEX D. title: Protein A–Gold: Nonspecific Binding and Cross-Contamination date: 2012-12-02 pages: extension: .txt txt: ./txt/cord-022200-hqc8r31t.txt cache: ./cache/cord-022200-hqc8r31t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022200-hqc8r31t.txt' === file2bib.sh === id: cord-020101-5rib7pe8 author: nan title: Cumulative Author Index for 2008 date: 2008-11-17 pages: extension: .txt txt: ./txt/cord-020101-5rib7pe8.txt cache: ./cache/cord-020101-5rib7pe8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-020101-5rib7pe8.txt' === file2bib.sh === id: cord-014852-6friw2ek author: Chumakov, S. P. title: Organization and regulation of nucleocytoplasmic transport date: 2010-04-24 pages: extension: .txt txt: ./txt/cord-014852-6friw2ek.txt cache: ./cache/cord-014852-6friw2ek.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-014852-6friw2ek.txt' === file2bib.sh === id: cord-023740-g84fa45m author: Oldstone, Michael B.A. title: Mimicry by Virus of Host Molecules: Implications for Autoimmune Disease date: 2014-06-27 pages: extension: .txt txt: ./txt/cord-023740-g84fa45m.txt cache: ./cache/cord-023740-g84fa45m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-023740-g84fa45m.txt' === file2bib.sh === id: cord-006331-s2qf98lj author: Spiridonova, V. A. title: Molecular recognition elements: DNA/RNA-aptamers to proteins date: 2010-05-23 pages: extension: .txt txt: ./txt/cord-006331-s2qf98lj.txt cache: ./cache/cord-006331-s2qf98lj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-006331-s2qf98lj.txt' === file2bib.sh === id: cord-003817-k3m72uxw author: Braun, Elisabeth title: Furin‐mediated protein processing in infectious diseases and cancer date: 2019-08-05 pages: extension: .txt txt: ./txt/cord-003817-k3m72uxw.txt cache: ./cache/cord-003817-k3m72uxw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003817-k3m72uxw.txt' === file2bib.sh === id: cord-014901-d9szap94 author: Permyakova, N. V. title: State of research in the field of the creation of plant vaccines for veterinary use date: 2015-01-04 pages: extension: .txt txt: ./txt/cord-014901-d9szap94.txt cache: ./cache/cord-014901-d9szap94.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-014901-d9szap94.txt' === file2bib.sh === id: cord-001726-d7iwkatn author: Henry, Kevin A. title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold date: 2015-08-04 pages: extension: .txt txt: ./txt/cord-001726-d7iwkatn.txt cache: ./cache/cord-001726-d7iwkatn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001726-d7iwkatn.txt' === file2bib.sh === id: cord-103528-3tib5o1m author: Ahmed, Asad title: DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-103528-3tib5o1m.txt cache: ./cache/cord-103528-3tib5o1m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103528-3tib5o1m.txt' === file2bib.sh === id: cord-022779-himray6q author: nan title: Abstracts of oral presentations date: 2005-06-10 pages: extension: .txt txt: ./txt/cord-022779-himray6q.txt cache: ./cache/cord-022779-himray6q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022779-himray6q.txt' === file2bib.sh === id: cord-014661-mrh2pbi6 author: Dumitrascu, Georgiana R. title: Critical physiological and pathological functions of Forkhead Box O tumor suppressors date: 2013-12-31 pages: extension: .txt txt: ./txt/cord-014661-mrh2pbi6.txt cache: ./cache/cord-014661-mrh2pbi6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-014661-mrh2pbi6.txt' === file2bib.sh === id: cord-024989-0o6agnrc author: Li, Qihao title: Prediction and analysis of key protein structures of 2019-nCoV date: 2020-05-12 pages: extension: .txt txt: ./txt/cord-024989-0o6agnrc.txt cache: ./cache/cord-024989-0o6agnrc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-024989-0o6agnrc.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-023647-dlqs8ay9 author: nan title: Sequences and topology date: 2003-03-21 pages: extension: .txt txt: ./txt/cord-023647-dlqs8ay9.txt cache: ./cache/cord-023647-dlqs8ay9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-023647-dlqs8ay9.txt' === file2bib.sh === id: cord-136540-2h2braww author: Buehler, Markus J. title: Liquified protein vibrations, classification and cross-paradigm de novo image generation using deep neural networks date: 2020-04-16 pages: extension: .txt txt: ./txt/cord-136540-2h2braww.txt cache: ./cache/cord-136540-2h2braww.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-136540-2h2braww.txt' === file2bib.sh === id: cord-023770-ymxapsv6 author: nan title: Closteroviridae date: 2011-11-23 pages: extension: .txt txt: ./txt/cord-023770-ymxapsv6.txt cache: ./cache/cord-023770-ymxapsv6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023770-ymxapsv6.txt' === file2bib.sh === id: cord-016419-v1f6dx3e author: Gupta, Varsha title: Production of Recombinant Pharmaceutical Proteins date: 2016-10-23 pages: extension: .txt txt: ./txt/cord-016419-v1f6dx3e.txt cache: ./cache/cord-016419-v1f6dx3e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-016419-v1f6dx3e.txt' === file2bib.sh === id: cord-018018-2yyv8vuy author: Rybicki, Ed title: History and Promise of Plant-Made Vaccines for Animals date: 2018-07-04 pages: extension: .txt txt: ./txt/cord-018018-2yyv8vuy.txt cache: ./cache/cord-018018-2yyv8vuy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-018018-2yyv8vuy.txt' === file2bib.sh === id: cord-017887-pj6pal35 author: OuYang, Bo title: Structural and Functional Properties of Viral Membrane Proteins date: 2018-06-29 pages: extension: .txt txt: ./txt/cord-017887-pj6pal35.txt cache: ./cache/cord-017887-pj6pal35.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-017887-pj6pal35.txt' === file2bib.sh === id: cord-017326-1caeui30 author: Seay, Montrell title: Digesting Oneself and Digesting Microbes: Autophagy as a Host Response to Viral Infection date: 2005 pages: extension: .txt txt: ./txt/cord-017326-1caeui30.txt cache: ./cache/cord-017326-1caeui30.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017326-1caeui30.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-017999-saxwqc2j author: Travers, Andrew A. title: Gene Regulation by HMGA and HMGB Chromosomal Proteins and Related Architectural DNA-Binding Proteins date: 2005 pages: extension: .txt txt: ./txt/cord-017999-saxwqc2j.txt cache: ./cache/cord-017999-saxwqc2j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017999-saxwqc2j.txt' === file2bib.sh === id: cord-048344-ps3mnpzq author: Zhu, Xiaowei title: ProCAT: a data analysis approach for protein microarrays date: 2006-11-16 pages: extension: .txt txt: ./txt/cord-048344-ps3mnpzq.txt cache: ./cache/cord-048344-ps3mnpzq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-048344-ps3mnpzq.txt' === file2bib.sh === id: cord-048471-7jszm1nd author: Salim, Omar title: Functional Analysis of the 5′ Genomic Sequence of a Bovine Norovirus date: 2008-05-14 pages: extension: .txt txt: ./txt/cord-048471-7jszm1nd.txt cache: ./cache/cord-048471-7jszm1nd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-048471-7jszm1nd.txt' === file2bib.sh === id: cord-103320-2rpr7aph author: Bhandari, Bikash K. title: Solubility-Weighted Index: fast and accurate prediction of protein solubility date: 2020-03-26 pages: extension: .txt txt: ./txt/cord-103320-2rpr7aph.txt cache: ./cache/cord-103320-2rpr7aph.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103320-2rpr7aph.txt' === file2bib.sh === id: cord-010681-tmpxs9og author: Dondapati, Srujan Kumar title: Cell-Free Protein Synthesis: A Promising Option for Future Drug Development date: 2020-03-20 pages: extension: .txt txt: ./txt/cord-010681-tmpxs9og.txt cache: ./cache/cord-010681-tmpxs9og.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-010681-tmpxs9og.txt' === file2bib.sh === id: cord-020757-q4ivezyq author: Saikumar, Pothana title: Apoptosis and Cell Death: Relevance to Lung date: 2010-05-21 pages: extension: .txt txt: ./txt/cord-020757-q4ivezyq.txt cache: ./cache/cord-020757-q4ivezyq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-020757-q4ivezyq.txt' === file2bib.sh === id: cord-034191-qqb2knmo author: Alayi, Tchilabalo D. title: Tandem Mass Tag-Based Serum Proteome Profiling for Biomarker Discovery in Young Duchenne Muscular Dystrophy Boys date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-034191-qqb2knmo.txt cache: ./cache/cord-034191-qqb2knmo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-034191-qqb2knmo.txt' === file2bib.sh === id: cord-018437-yjvwa1ot author: Mitchell, Michael title: Taxonomy date: 2013-08-26 pages: extension: .txt txt: ./txt/cord-018437-yjvwa1ot.txt cache: ./cache/cord-018437-yjvwa1ot.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018437-yjvwa1ot.txt' === file2bib.sh === id: cord-034823-ogwjzfgf author: Guo, Hao-Bo title: A Suggestion of Converting Protein Intrinsic Disorder to Structural Entropy Using Shannon’s Information Theory date: 2019-06-14 pages: extension: .txt txt: ./txt/cord-034823-ogwjzfgf.txt cache: ./cache/cord-034823-ogwjzfgf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-034823-ogwjzfgf.txt' === file2bib.sh === id: cord-020664-m47ejlsn author: Schlüter, Klaus-Dieter title: Intrakrine, parakrine und autokrine Funktionen des PTH/PTHrP-Systems date: 2006 pages: extension: .txt txt: ./txt/cord-020664-m47ejlsn.txt cache: ./cache/cord-020664-m47ejlsn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-020664-m47ejlsn.txt' === file2bib.sh === id: cord-031937-qhlatg84 author: Verma, Anukriti title: Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-031937-qhlatg84.txt cache: ./cache/cord-031937-qhlatg84.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-031937-qhlatg84.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41852 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43398 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-017866-h5ttoo0z author: Bowman, Grant R. title: Biogenesis of Dense-Core Secretory Granules date: 2010-05-27 pages: extension: .txt txt: ./txt/cord-017866-h5ttoo0z.txt cache: ./cache/cord-017866-h5ttoo0z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-017866-h5ttoo0z.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 84. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42820 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 84. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 83. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-018969-0zrnfaad author: Giese, Matthias title: Types of Recombinant Vaccines date: 2015-09-24 pages: extension: .txt txt: ./txt/cord-018969-0zrnfaad.txt cache: ./cache/cord-018969-0zrnfaad.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018969-0zrnfaad.txt' === file2bib.sh === id: cord-171099-d0qr84xg author: Buehler, Markus J. title: Nanomechanical sonification of the 2019-nCoV coronavirus spike protein through a materiomusical approach date: 2020-03-30 pages: extension: .txt txt: ./txt/cord-171099-d0qr84xg.txt cache: ./cache/cord-171099-d0qr84xg.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-171099-d0qr84xg.txt' === file2bib.sh === id: cord-243806-26n22jbx author: Vandelli, Andrea title: Structural analysis of SARS-CoV-2 and prediction of the human interactome date: 2020-03-30 pages: extension: .txt txt: ./txt/cord-243806-26n22jbx.txt cache: ./cache/cord-243806-26n22jbx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-243806-26n22jbx.txt' /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-016594-lj0us1dq author: Flower, Darren R. title: Identification of Candidate Vaccine Antigens In Silico date: 2012-09-28 pages: extension: .txt txt: ./txt/cord-016594-lj0us1dq.txt cache: ./cache/cord-016594-lj0us1dq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016594-lj0us1dq.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-029957-q7v5gli8 author: Prabhu, D. title: In silico Functional Annotation and Characterization of Hypothetical Proteins from Serratia marcescens FGI94 date: 2020-07-31 pages: extension: .txt txt: ./txt/cord-029957-q7v5gli8.txt cache: ./cache/cord-029957-q7v5gli8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-029957-q7v5gli8.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-104279-choywmwd author: nan title: Membrane protein sorting in the yeast secretory pathway: evidence that the vacuole may be the default compartment date: 1992-10-01 pages: extension: .txt txt: ./txt/cord-104279-choywmwd.txt cache: ./cache/cord-104279-choywmwd.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-104279-choywmwd.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41896 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 83. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42601 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-018647-bveks6t1 author: Butnariu, Monica title: Plant Nanobionics: Application of Nanobiosensors in Plant Biology date: 2019-10-01 pages: extension: .txt txt: ./txt/cord-018647-bveks6t1.txt cache: ./cache/cord-018647-bveks6t1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-018647-bveks6t1.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44437 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-190540-zf5ksac2 author: Rakshit, Kausik title: An effective approach to reduce the penetration potential of Sars-Cov-2 and other viruses by spike protein: Through surface particle electrostatic charge negotiation date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-190540-zf5ksac2.txt cache: ./cache/cord-190540-zf5ksac2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-190540-zf5ksac2.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43924 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-023726-2fduzqyb author: STRAUSS, JAMES H. title: The Structure of Viruses date: 2012-07-27 pages: extension: .txt txt: ./txt/cord-023726-2fduzqyb.txt cache: ./cache/cord-023726-2fduzqyb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-023726-2fduzqyb.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 82. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-252304-lwiulri7 author: Fragnoud, Romain title: Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue date: 2015-11-14 pages: extension: .txt txt: ./txt/cord-252304-lwiulri7.txt cache: ./cache/cord-252304-lwiulri7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-252304-lwiulri7.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-021626-ck2kybtp author: Walker-Smith, John title: Dietary protein intolerance date: 2013-10-21 pages: extension: .txt txt: ./txt/cord-021626-ck2kybtp.txt cache: ./cache/cord-021626-ck2kybtp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 18 resourceName b'cord-021626-ck2kybtp.txt' /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-022499-7d58f1k3 author: Mall, Sanjay title: Transmembrane α helices date: 2004-01-07 pages: extension: .txt txt: ./txt/cord-022499-7d58f1k3.txt cache: ./cache/cord-022499-7d58f1k3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022499-7d58f1k3.txt' === file2bib.sh === id: cord-033010-o5kiadfm author: Durojaye, Olanrewaju Ayodeji title: Potential therapeutic target identification in the novel 2019 coronavirus: insight from homology modeling and blind docking study date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-033010-o5kiadfm.txt cache: ./cache/cord-033010-o5kiadfm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-033010-o5kiadfm.txt' /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-023865-6rafp3x3 author: Surjit, Milan title: The Nucleocapsid Protein of the SARS Coronavirus: Structure, Function and Therapeutic Potential date: 2009-07-22 pages: extension: .txt txt: ./txt/cord-023865-6rafp3x3.txt cache: ./cache/cord-023865-6rafp3x3.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-023865-6rafp3x3.txt' === file2bib.sh === id: cord-253987-83h861lp author: Tada, Takuya title: A soluble ACE2 microbody protein fused to a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2 infection in cell culture date: 2020-09-17 pages: extension: .txt txt: ./txt/cord-253987-83h861lp.txt cache: ./cache/cord-253987-83h861lp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-253987-83h861lp.txt' === file2bib.sh === id: cord-033333-880jx1bt author: Salman, Saad title: In silico analysis of protein/peptide-based inhalers against SARS-CoV-2 date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-033333-880jx1bt.txt cache: ./cache/cord-033333-880jx1bt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-033333-880jx1bt.txt' === file2bib.sh === id: cord-018265-twp33bb6 author: Becker, Pablo D. title: Community-acquired pneumonia: paving the way towards new vaccination concepts date: 2007 pages: extension: .txt txt: ./txt/cord-018265-twp33bb6.txt cache: ./cache/cord-018265-twp33bb6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018265-twp33bb6.txt' === file2bib.sh === id: cord-150183-zzzyewjb author: Phillips, J. C. title: Synchronized Attachment and the Darwinian Evolution of Coronaviruses CoV-1 and CoV-2 date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-150183-zzzyewjb.txt cache: ./cache/cord-150183-zzzyewjb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-150183-zzzyewjb.txt' === file2bib.sh === id: cord-048360-n9sih438 author: Villard, Viviane title: Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif date: 2007-07-25 pages: extension: .txt txt: ./txt/cord-048360-n9sih438.txt cache: ./cache/cord-048360-n9sih438.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-048360-n9sih438.txt' === file2bib.sh === id: cord-103430-x6zzuu7v author: Contu, Lara title: Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay date: 2020-10-12 pages: extension: .txt txt: ./txt/cord-103430-x6zzuu7v.txt cache: ./cache/cord-103430-x6zzuu7v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-103430-x6zzuu7v.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-021393-9loesliv author: Meade, H.M. title: EXPRESSION OF RECOMBINANT PROTEINS IN THE MILK OF TRANSGENIC ANIMALS date: 2007-09-02 pages: extension: .txt txt: ./txt/cord-021393-9loesliv.txt cache: ./cache/cord-021393-9loesliv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-021393-9loesliv.txt' === file2bib.sh === id: cord-103255-4k13re9y author: Daniell, Henry title: Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants date: 2001-05-01 pages: extension: .txt txt: ./txt/cord-103255-4k13re9y.txt cache: ./cache/cord-103255-4k13re9y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103255-4k13re9y.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45745 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46103 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-103509-hynnba03 author: Wong, Ten-Tsao title: A self-assembled protein nanoparticle serving as a one-shot vaccine carrier date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-103509-hynnba03.txt cache: ./cache/cord-103509-hynnba03.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103509-hynnba03.txt' === file2bib.sh === id: cord-193133-puqcbf8t author: Piplani, Sakshi title: In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-193133-puqcbf8t.txt cache: ./cache/cord-193133-puqcbf8t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-193133-puqcbf8t.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46590 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48668 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-020235-stcrozdw author: nan title: Abstracts of Papers Presented at the 38th Meeting of the Deutsche Gesellschaft für Hygiene und Mikrobiologie, Virology Section, Göttingen, 5.–8.10.1981 date: 2012-03-15 pages: extension: .txt txt: ./txt/cord-020235-stcrozdw.txt cache: ./cache/cord-020235-stcrozdw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-020235-stcrozdw.txt' === file2bib.sh === id: cord-021772-5v4gor2v author: Levine, Gwendolyn J. title: Cerebrospinal Fluid and Central Nervous System Cytology date: 2019-05-31 pages: extension: .txt txt: ./txt/cord-021772-5v4gor2v.txt cache: ./cache/cord-021772-5v4gor2v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-021772-5v4gor2v.txt' === file2bib.sh === id: cord-018963-2lia97db author: Xu, Ying title: Protein Structure Prediction by Protein Threading date: 2010-04-29 pages: extension: .txt txt: ./txt/cord-018963-2lia97db.txt cache: ./cache/cord-018963-2lia97db.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-018963-2lia97db.txt' === file2bib.sh === id: cord-003435-ke0az7nf author: Schlake, Thomas title: mRNA as novel technology for passive immunotherapy date: 2018-10-17 pages: extension: .txt txt: ./txt/cord-003435-ke0az7nf.txt cache: ./cache/cord-003435-ke0az7nf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003435-ke0az7nf.txt' === file2bib.sh === id: cord-020788-a33vcapl author: Gottardi, Cara J. title: Signals and Mechanisms of Sorting in Epithelial Polarity date: 2008-05-22 pages: extension: .txt txt: ./txt/cord-020788-a33vcapl.txt cache: ./cache/cord-020788-a33vcapl.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-020788-a33vcapl.txt' === file2bib.sh === id: cord-222664-4qyrtzhu author: Coban, Mathew title: Attacking COVID-19 Progression using Multi-Drug Therapy for Synergetic Target Engagement date: 2020-07-06 pages: extension: .txt txt: ./txt/cord-222664-4qyrtzhu.txt cache: ./cache/cord-222664-4qyrtzhu.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-222664-4qyrtzhu.txt' === file2bib.sh === id: cord-024193-khdvj6t5 author: Zhang, Hong title: Peptide Arrays date: 2012-01-17 pages: extension: .txt txt: ./txt/cord-024193-khdvj6t5.txt cache: ./cache/cord-024193-khdvj6t5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-024193-khdvj6t5.txt' === file2bib.sh === id: cord-017817-ztp7w9yh author: Land, Walter Gottlieb title: Cell-Autonomous (Cell-Intrinsic) Stress Responses date: 2018-03-28 pages: extension: .txt txt: ./txt/cord-017817-ztp7w9yh.txt cache: ./cache/cord-017817-ztp7w9yh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017817-ztp7w9yh.txt' === file2bib.sh === id: cord-000372-wzwpyvll author: Castelló, Alfredo title: The Multifaceted Poliovirus 2A Protease: Regulation of Gene Expression by Picornavirus Proteases date: 2011-04-14 pages: extension: .txt txt: ./txt/cord-000372-wzwpyvll.txt cache: ./cache/cord-000372-wzwpyvll.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-000372-wzwpyvll.txt' === file2bib.sh === id: cord-252576-1ec545o2 author: Wu, Xiangli title: An antifungal defensin from Phaseolus vulgaris cv. ‘Cloud Bean’ date: 2011-01-15 pages: extension: .txt txt: ./txt/cord-252576-1ec545o2.txt cache: ./cache/cord-252576-1ec545o2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-252576-1ec545o2.txt' === file2bib.sh === id: cord-016448-7imgztwe author: Frishman, D. title: Protein-protein interactions: analysis and prediction date: 2009-10-01 pages: extension: .txt txt: ./txt/cord-016448-7imgztwe.txt cache: ./cache/cord-016448-7imgztwe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-016448-7imgztwe.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51961 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52347 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49141 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49791 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-022354-aqtceqqo author: HUNTER, ERIC title: Membrane Insertion and Transport of Viral Glycoproteins: A Mutational Analysis date: 2012-12-02 pages: extension: .txt txt: ./txt/cord-022354-aqtceqqo.txt cache: ./cache/cord-022354-aqtceqqo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022354-aqtceqqo.txt' === file2bib.sh === id: cord-193489-u6ewlh16 author: Wang, Rui title: Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine date: 2020-04-29 pages: extension: .txt txt: ./txt/cord-193489-u6ewlh16.txt cache: ./cache/cord-193489-u6ewlh16.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-193489-u6ewlh16.txt' === file2bib.sh === id: cord-104282-90t1m430 author: nan title: Microsomal aldehyde dehydrogenase is localized to the endoplasmic reticulum via its carboxyl-terminal 35 amino acids date: 1994-09-02 pages: extension: .txt txt: ./txt/cord-104282-90t1m430.txt cache: ./cache/cord-104282-90t1m430.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104282-90t1m430.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-022235-6ircruag author: Pugsley, Anthony P. title: Later stages in the eukaryotic secretory pathway date: 2012-12-02 pages: extension: .txt txt: ./txt/cord-022235-6ircruag.txt cache: ./cache/cord-022235-6ircruag.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022235-6ircruag.txt' === file2bib.sh === id: cord-253844-y6xdcf20 author: Yesudhas, Dhanusha title: COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-253844-y6xdcf20.txt cache: ./cache/cord-253844-y6xdcf20.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-253844-y6xdcf20.txt' === file2bib.sh === id: cord-196265-mvnkkcow author: M'esz'aros, B'alint title: Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications date: 2020-04-21 pages: extension: .txt txt: ./txt/cord-196265-mvnkkcow.txt cache: ./cache/cord-196265-mvnkkcow.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-196265-mvnkkcow.txt' === file2bib.sh === id: cord-034406-i1hbx3pz author: Matthews, Abigail A. title: Developing inhaled protein therapeutics for lung diseases date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-034406-i1hbx3pz.txt cache: ./cache/cord-034406-i1hbx3pz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-034406-i1hbx3pz.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54138 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53589 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52729 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52466 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52853 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54075 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53368 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51237 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53851 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-257584-v38tjof3 author: Fahmi, Muhamad title: Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV date: 2020-03-03 pages: extension: .txt txt: ./txt/cord-257584-v38tjof3.txt cache: ./cache/cord-257584-v38tjof3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257584-v38tjof3.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54073 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54208 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54222 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53937 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-029747-8f463wz0 author: Viedma-Poyatos, Álvaro title: Type III intermediate filaments as targets and effectors of electrophiles and oxidants date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-029747-8f463wz0.txt cache: ./cache/cord-029747-8f463wz0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-029747-8f463wz0.txt' === file2bib.sh === id: cord-021500-sy6lnt7b author: Jean Harry, G. title: Myelination, Dysmyelination, and Demyelination date: 2007-05-09 pages: extension: .txt txt: ./txt/cord-021500-sy6lnt7b.txt cache: ./cache/cord-021500-sy6lnt7b.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-021500-sy6lnt7b.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55220 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-254909-8zgvovu4 author: Srivastava, Rajneesh title: Serum profiling of leptospirosis patients to investigate proteomic alterations() date: 2012-12-05 pages: extension: .txt txt: ./txt/cord-254909-8zgvovu4.txt cache: ./cache/cord-254909-8zgvovu4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-254909-8zgvovu4.txt' === file2bib.sh === id: cord-252147-bvtchcbt author: Domingo-Espín, Joan title: Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles date: 2011-11-15 pages: extension: .txt txt: ./txt/cord-252147-bvtchcbt.txt cache: ./cache/cord-252147-bvtchcbt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-252147-bvtchcbt.txt' === file2bib.sh === id: cord-254100-u6x5zd4i author: Taliansky, M.E. title: Involvement of the Plant Nucleolus in Virus and Viroid Infections: Parallels with Animal Pathosystems date: 2010-10-15 pages: extension: .txt txt: ./txt/cord-254100-u6x5zd4i.txt cache: ./cache/cord-254100-u6x5zd4i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-254100-u6x5zd4i.txt' === file2bib.sh === id: cord-261472-qcu73sdu author: Yao, Yong Xiu title: Cleavage and Serum Reactivity of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein date: 2004-07-01 pages: extension: .txt txt: ./txt/cord-261472-qcu73sdu.txt cache: ./cache/cord-261472-qcu73sdu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-261472-qcu73sdu.txt' === file2bib.sh === id: cord-252536-gfx4cq03 author: Bieniossek, Christoph title: MultiBac: expanding the research toolbox for multiprotein complexes date: 2011-12-07 pages: extension: .txt txt: ./txt/cord-252536-gfx4cq03.txt cache: ./cache/cord-252536-gfx4cq03.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252536-gfx4cq03.txt' === file2bib.sh === id: cord-008556-oetrdm8g author: Kozak, Marilyn title: Regulation of Protein Synthesis in Virus-Infected Animal Cells date: 2008-03-01 pages: extension: .txt txt: ./txt/cord-008556-oetrdm8g.txt cache: ./cache/cord-008556-oetrdm8g.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-008556-oetrdm8g.txt' === file2bib.sh === id: cord-026012-r0w0jbpg author: TENNANT, BUD C. title: Gastrointestinal Function date: 2014-06-27 pages: extension: .txt txt: ./txt/cord-026012-r0w0jbpg.txt cache: ./cache/cord-026012-r0w0jbpg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-026012-r0w0jbpg.txt' === file2bib.sh === id: cord-254107-02bik024 author: Hillisch, Alexander title: Utility of homology models in the drug discovery process date: 2004-08-31 pages: extension: .txt txt: ./txt/cord-254107-02bik024.txt cache: ./cache/cord-254107-02bik024.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254107-02bik024.txt' === file2bib.sh === id: cord-257392-u6jy6w1m author: Zhao, Yanfeng title: Proteomic analysis of primary duck hepatocytes infected with duck hepatitis B virus date: 2010-06-07 pages: extension: .txt txt: ./txt/cord-257392-u6jy6w1m.txt cache: ./cache/cord-257392-u6jy6w1m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257392-u6jy6w1m.txt' === file2bib.sh === id: cord-257802-vgizgq2y author: Uttamchandani, Mahesh title: Applications of microarrays in pathogen detection and biodefence date: 2008-11-12 pages: extension: .txt txt: ./txt/cord-257802-vgizgq2y.txt cache: ./cache/cord-257802-vgizgq2y.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-257802-vgizgq2y.txt' === file2bib.sh === id: cord-256340-w4z5avld author: Bailer, SM title: Connecting viral with cellular interactomes date: 2009-07-24 pages: extension: .txt txt: ./txt/cord-256340-w4z5avld.txt cache: ./cache/cord-256340-w4z5avld.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-256340-w4z5avld.txt' === file2bib.sh === id: cord-262268-gm99cadh author: Wang, Jingqiang title: Assessment of Immunoreactive Synthetic Peptides from the Structural Proteins of Severe Acute Respiratory Syndrome Coronavirus date: 2003-12-01 pages: extension: .txt txt: ./txt/cord-262268-gm99cadh.txt cache: ./cache/cord-262268-gm99cadh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-262268-gm99cadh.txt' === file2bib.sh === id: cord-199630-2lmwnfda author: Ray, Sumanta title: Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs date: 2020-07-05 pages: extension: .txt txt: ./txt/cord-199630-2lmwnfda.txt cache: ./cache/cord-199630-2lmwnfda.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-199630-2lmwnfda.txt' === file2bib.sh === id: cord-264392-he1vekrt author: Lambeth, L. S. title: Complete genome sequence of Nariva virus, a rodent paramyxovirus date: 2008-12-23 pages: extension: .txt txt: ./txt/cord-264392-he1vekrt.txt cache: ./cache/cord-264392-he1vekrt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-264392-he1vekrt.txt' === file2bib.sh === id: cord-256325-q70rky3r author: Stewart, Cameron R. title: A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease date: 2017-07-04 pages: extension: .txt txt: ./txt/cord-256325-q70rky3r.txt cache: ./cache/cord-256325-q70rky3r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-256325-q70rky3r.txt' === file2bib.sh === id: cord-262043-66qle52a author: Basit, Abdul title: Truncated human angiotensin converting enzyme 2; a potential inhibitor of SARS-CoV-2 spike glycoprotein and potent COVID-19 therapeutic agent date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-262043-66qle52a.txt cache: ./cache/cord-262043-66qle52a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262043-66qle52a.txt' === file2bib.sh === id: cord-259505-7hiss0j3 author: Kong, Qingming title: Proteomic analysis of purified coronavirus infectious bronchitis virus particles date: 2010-06-09 pages: extension: .txt txt: ./txt/cord-259505-7hiss0j3.txt cache: ./cache/cord-259505-7hiss0j3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-259505-7hiss0j3.txt' === file2bib.sh === id: cord-258468-52gej3co author: Marcekova, Zuzana title: Heterologous expression of full-length capsid protein of porcine circovirus 2 in Escherichia coli and its potential use for detection of antibodies date: 2009-08-05 pages: extension: .txt txt: ./txt/cord-258468-52gej3co.txt cache: ./cache/cord-258468-52gej3co.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-258468-52gej3co.txt' === file2bib.sh === id: cord-265087-g4k6pc82 author: Munteanu, Cristian Robert title: Natural/random protein classification models based on star network topological indices date: 2008-10-21 pages: extension: .txt txt: ./txt/cord-265087-g4k6pc82.txt cache: ./cache/cord-265087-g4k6pc82.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-265087-g4k6pc82.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-256316-1odgm6hm author: Godet, Murielle title: TGEV corona virus ORF4 encodes a membrane protein that is incorporated into virions date: 1992-06-30 pages: extension: .txt txt: ./txt/cord-256316-1odgm6hm.txt cache: ./cache/cord-256316-1odgm6hm.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-256316-1odgm6hm.txt' === file2bib.sh === id: cord-264031-0y7xbgun author: Wierbowski, Shayne D. title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-264031-0y7xbgun.txt cache: ./cache/cord-264031-0y7xbgun.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-264031-0y7xbgun.txt' === file2bib.sh === id: cord-258784-9bdd9krr author: Wei, Chiming title: New technology and clinical applications of nanomedicine: Highlights of the second annual meeting of the American Academy of Nanomedicine (Part I) date: 2006-12-31 pages: extension: .txt txt: ./txt/cord-258784-9bdd9krr.txt cache: ./cache/cord-258784-9bdd9krr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258784-9bdd9krr.txt' === file2bib.sh === id: cord-262904-0b0ljjq1 author: Lon, Jerome Rumdon title: Prediction and evolution of B cell epitopes of surface protein in SARS-CoV-2 date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-262904-0b0ljjq1.txt cache: ./cache/cord-262904-0b0ljjq1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-262904-0b0ljjq1.txt' === file2bib.sh === id: cord-270594-62xotol3 author: He, Lei title: Identification and characterization of vp7 gene in Bombyx mori cytoplasmic polyhedrosis virus date: 2017-09-05 pages: extension: .txt txt: ./txt/cord-270594-62xotol3.txt cache: ./cache/cord-270594-62xotol3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-270594-62xotol3.txt' === file2bib.sh === id: cord-259260-qcfgigga author: Ibrahim, Ibrahim M. title: GRP78: A cell's response to stress date: 2019-06-01 pages: extension: .txt txt: ./txt/cord-259260-qcfgigga.txt cache: ./cache/cord-259260-qcfgigga.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-259260-qcfgigga.txt' === file2bib.sh === id: cord-261375-6fu3dzi9 author: Hoppe, Sebastian title: Microarray-based method for screening of immunogenic proteins from bacteria date: 2012-03-21 pages: extension: .txt txt: ./txt/cord-261375-6fu3dzi9.txt cache: ./cache/cord-261375-6fu3dzi9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-261375-6fu3dzi9.txt' === file2bib.sh === id: cord-274056-9t3kneoo author: Abd Elwahaab, Marwa A. title: A Statistical Similarity/Dissimilarity Analysis of Protein Sequences Based on a Novel Group Representative Vector date: 2019-05-08 pages: extension: .txt txt: ./txt/cord-274056-9t3kneoo.txt cache: ./cache/cord-274056-9t3kneoo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274056-9t3kneoo.txt' === file2bib.sh === id: cord-274366-t138l6px author: Benetti, Elisa title: ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-274366-t138l6px.txt cache: ./cache/cord-274366-t138l6px.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274366-t138l6px.txt' === file2bib.sh === id: cord-260869-rym2ik0o author: Lemmermeyer, Tanja title: Characterization of monoclonal antibodies against feline coronavirus accessory protein 7b date: 2016-02-29 pages: extension: .txt txt: ./txt/cord-260869-rym2ik0o.txt cache: ./cache/cord-260869-rym2ik0o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260869-rym2ik0o.txt' === file2bib.sh === id: cord-277811-j58qvyum author: Mehrani, Hossein title: Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis date: 2011-01-07 pages: extension: .txt txt: ./txt/cord-277811-j58qvyum.txt cache: ./cache/cord-277811-j58qvyum.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-277811-j58qvyum.txt' === file2bib.sh === id: cord-275124-7l53bvp1 author: Yao, Minghui title: A potential treatment for COVID-19 based on modal characteristics and dynamic responses analysis of 2019-nCoV date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-275124-7l53bvp1.txt cache: ./cache/cord-275124-7l53bvp1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275124-7l53bvp1.txt' === file2bib.sh === id: cord-266481-9afb0yvt author: Naskalska, Antonina title: Membrane Protein of Human Coronavirus NL63 Is Responsible for Interaction with the Adhesion Receptor date: 2019-07-17 pages: extension: .txt txt: ./txt/cord-266481-9afb0yvt.txt cache: ./cache/cord-266481-9afb0yvt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-266481-9afb0yvt.txt' === file2bib.sh === id: cord-272260-88l9bq4i author: Han, L.Y. title: Prediction of functional class of novel viral proteins by a statistical learning method irrespective of sequence similarity date: 2005-01-05 pages: extension: .txt txt: ./txt/cord-272260-88l9bq4i.txt cache: ./cache/cord-272260-88l9bq4i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272260-88l9bq4i.txt' === file2bib.sh === id: cord-268416-8hw80qx8 author: Grunewald, Matthew E. title: The coronavirus nucleocapsid protein is ADP-ribosylated date: 2018-04-01 pages: extension: .txt txt: ./txt/cord-268416-8hw80qx8.txt cache: ./cache/cord-268416-8hw80qx8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268416-8hw80qx8.txt' === file2bib.sh === id: cord-279432-aik5bo6o author: Digard, Paul title: Complex formation between influenza virus polymerase proteins expressed in Xenopus oocytes date: 1989-07-31 pages: extension: .txt txt: ./txt/cord-279432-aik5bo6o.txt cache: ./cache/cord-279432-aik5bo6o.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-279432-aik5bo6o.txt' === file2bib.sh === id: cord-266617-z8uecyl6 author: Pavesi, Angelo title: Asymmetric evolution in viral overlapping genes is a source of selective protein adaptation date: 2019-04-03 pages: extension: .txt txt: ./txt/cord-266617-z8uecyl6.txt cache: ./cache/cord-266617-z8uecyl6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-266617-z8uecyl6.txt' === file2bib.sh === id: cord-266543-ng9zr299 author: Klebe, Gerhard title: Virtual ligand screening: strategies, perspectives and limitations date: 2006-06-20 pages: extension: .txt txt: ./txt/cord-266543-ng9zr299.txt cache: ./cache/cord-266543-ng9zr299.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-266543-ng9zr299.txt' === file2bib.sh === id: cord-031957-df4luh5v author: dos Santos-Silva, Carlos André title: Plant Antimicrobial Peptides: State of the Art, In Silico Prediction and Perspectives in the Omics Era date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-031957-df4luh5v.txt cache: ./cache/cord-031957-df4luh5v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-031957-df4luh5v.txt' === file2bib.sh === id: cord-260440-e63pgcir author: Dinjaski, Nina title: Smart polyhydroxyalkanoate nanobeads by protein based functionalization date: 2015-02-24 pages: extension: .txt txt: ./txt/cord-260440-e63pgcir.txt cache: ./cache/cord-260440-e63pgcir.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-260440-e63pgcir.txt' === file2bib.sh === id: cord-266977-5swwc6kr author: Secker, Thomas.J. title: Journal of Hospital Infection A cold water, ultrasonic activated stream efficiently removes proteins and prion-associated amyloid from surgical stainless steel date: 2020-09-19 pages: extension: .txt txt: ./txt/cord-266977-5swwc6kr.txt cache: ./cache/cord-266977-5swwc6kr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-266977-5swwc6kr.txt' === file2bib.sh === id: cord-275993-isff6lp2 author: Han, Dong P title: Development of a safe neutralization assay for SARS-CoV and characterization of S-glycoprotein date: 2004-08-15 pages: extension: .txt txt: ./txt/cord-275993-isff6lp2.txt cache: ./cache/cord-275993-isff6lp2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-275993-isff6lp2.txt' === file2bib.sh === id: cord-279106-3ffa9djf author: Syatila Ab Ghani, Nur title: Side chain similarity comparisons for integrated drug repositioning and potential toxicity assessments in epidemic response scenarios: the case for COVID-19 date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-279106-3ffa9djf.txt cache: ./cache/cord-279106-3ffa9djf.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-279106-3ffa9djf.txt' === file2bib.sh === id: cord-276966-wmelyonk author: Roe, Kevin title: A proposed treatment for pathogenic enveloped viruses having high rates of mutation or replication date: 2020-07-08 pages: extension: .txt txt: ./txt/cord-276966-wmelyonk.txt cache: ./cache/cord-276966-wmelyonk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-276966-wmelyonk.txt' === file2bib.sh === id: cord-282604-xp71rkxc author: Nikolaev, EN title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein date: 2020-05-25 pages: extension: .txt txt: ./txt/cord-282604-xp71rkxc.txt cache: ./cache/cord-282604-xp71rkxc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-282604-xp71rkxc.txt' === file2bib.sh === id: cord-258489-pyfc7jde author: Lico, Chiara title: Viral vectors for production of recombinant proteins in plants date: 2008-03-10 pages: extension: .txt txt: ./txt/cord-258489-pyfc7jde.txt cache: ./cache/cord-258489-pyfc7jde.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-258489-pyfc7jde.txt' === file2bib.sh === id: cord-272241-2fwz8z8n author: Kumar, Amit title: Exploring the SARS-CoV-2 structural proteins for multi-epitope vaccine development: an in-silico approach date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-272241-2fwz8z8n.txt cache: ./cache/cord-272241-2fwz8z8n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272241-2fwz8z8n.txt' === file2bib.sh === id: cord-281005-6gi18vka author: Singh, Praveen Kumar title: Mutations in SARS-CoV-2 Leading to Antigenic Variations in Spike Protein: A Challenge in Vaccine Development date: 2020-09-01 pages: extension: .txt txt: ./txt/cord-281005-6gi18vka.txt cache: ./cache/cord-281005-6gi18vka.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281005-6gi18vka.txt' === file2bib.sh === id: cord-266444-rw94yls8 author: Dominguez Andres, Ana title: SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-266444-rw94yls8.txt cache: ./cache/cord-266444-rw94yls8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-266444-rw94yls8.txt' === file2bib.sh === id: cord-279463-bli8hwda author: Lipp, Joachim title: The membrane-spanning segment of invariant chain (Iγ) contains a potentially cleavable signal sequence date: 1986-09-26 pages: extension: .txt txt: ./txt/cord-279463-bli8hwda.txt cache: ./cache/cord-279463-bli8hwda.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-279463-bli8hwda.txt' === file2bib.sh === id: cord-274424-juj71nc5 author: Pulford, David J. title: Intracellular processing of the porcine coronavirus transmissible gastroenteritis virus spike protein expressed by recombinant vaccinia virus date: 1991-06-30 pages: extension: .txt txt: ./txt/cord-274424-juj71nc5.txt cache: ./cache/cord-274424-juj71nc5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-274424-juj71nc5.txt' === file2bib.sh === id: cord-261159-9pkg7mbh author: Regnier, Fred E. title: Chromatography of complex protein mixtures date: 1987-07-17 pages: extension: .txt txt: ./txt/cord-261159-9pkg7mbh.txt cache: ./cache/cord-261159-9pkg7mbh.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-261159-9pkg7mbh.txt' === file2bib.sh === id: cord-279418-3r1ijafm author: Nevers, Quentin title: Negri bodies and other virus membrane-less replication compartments() date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-279418-3r1ijafm.txt cache: ./cache/cord-279418-3r1ijafm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279418-3r1ijafm.txt' === file2bib.sh === id: cord-271693-7tg21up3 author: Zheng, Fan title: Identifying persistent structures in multiscale ‘omics data date: 2020-10-03 pages: extension: .txt txt: ./txt/cord-271693-7tg21up3.txt cache: ./cache/cord-271693-7tg21up3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271693-7tg21up3.txt' === file2bib.sh === id: cord-270514-36k9xo7f author: van der Woude, Roosmarijn title: Drivers of recombinant soluble influenza A virus hemagglutinin and neuraminidase expression in mammalian cells date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-270514-36k9xo7f.txt cache: ./cache/cord-270514-36k9xo7f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270514-36k9xo7f.txt' === file2bib.sh === id: cord-276456-oa6hh7ky author: Collins, R.N. title: 5.14 The Biophysics of Membrane Fusion date: 2012-05-03 pages: extension: .txt txt: ./txt/cord-276456-oa6hh7ky.txt cache: ./cache/cord-276456-oa6hh7ky.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-276456-oa6hh7ky.txt' === file2bib.sh === id: cord-279598-xzionafe author: Chang, Chia-Yu title: Identification of Neutralizing Monoclonal Antibodies Targeting Novel Conformational Epitopes of the Porcine Epidemic Diarrhoea Virus Spike Protein date: 2019-02-21 pages: extension: .txt txt: ./txt/cord-279598-xzionafe.txt cache: ./cache/cord-279598-xzionafe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-279598-xzionafe.txt' === file2bib.sh === id: cord-275023-0z219rcy author: Cerofolini, Linda title: Orientation of immobilized antigens on common surfaces by a simple computational model: Exposition of SARS-CoV-2 Spike protein RBD epitopes date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-275023-0z219rcy.txt cache: ./cache/cord-275023-0z219rcy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275023-0z219rcy.txt' === file2bib.sh === id: cord-280679-jj3wzojy author: Marblestone, Jeffrey G. title: Comparison of SUMO fusion technology with traditional gene fusion systems: Enhanced expression and solubility with SUMO date: 2006-01-01 pages: extension: .txt txt: ./txt/cord-280679-jj3wzojy.txt cache: ./cache/cord-280679-jj3wzojy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280679-jj3wzojy.txt' === file2bib.sh === id: cord-265887-g5zhoyo9 author: Mukherjee, Shruti title: Host-membrane interacting interface of the SARS coronavirus envelope protein: Immense functional potential of C-terminal domain date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-265887-g5zhoyo9.txt cache: ./cache/cord-265887-g5zhoyo9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-265887-g5zhoyo9.txt' === file2bib.sh === id: cord-273019-hbpfz8rt author: Glingston, R. Sahaya title: Organelle dynamics and viral infections: at cross roads date: 2018-06-25 pages: extension: .txt txt: ./txt/cord-273019-hbpfz8rt.txt cache: ./cache/cord-273019-hbpfz8rt.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-273019-hbpfz8rt.txt' === file2bib.sh === id: cord-270273-a4iu9qg6 author: Ruiz, Federico M. title: Chicken GRIFIN: Structural characterization in crystals and in solution date: 2017-12-15 pages: extension: .txt txt: ./txt/cord-270273-a4iu9qg6.txt cache: ./cache/cord-270273-a4iu9qg6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-270273-a4iu9qg6.txt' === file2bib.sh === id: cord-279586-likfvwwj author: Jin, Jian title: Effects of Sonication on the In vitro Digestibility and Structural Properties of Buckwheat Protein Isolates date: 2020-09-17 pages: extension: .txt txt: ./txt/cord-279586-likfvwwj.txt cache: ./cache/cord-279586-likfvwwj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-279586-likfvwwj.txt' === file2bib.sh === id: cord-014462-11ggaqf1 author: nan title: Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh date: 2011-04-21 pages: extension: .txt txt: ./txt/cord-014462-11ggaqf1.txt cache: ./cache/cord-014462-11ggaqf1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-014462-11ggaqf1.txt' === file2bib.sh === id: cord-286635-7aflpgxd author: YANG, Yong-xin title: Comparative Proteomic Analysis of Plasma from Clinical Healthy Cows and Mastitic Cows date: 2009-10-31 pages: extension: .txt txt: ./txt/cord-286635-7aflpgxd.txt cache: ./cache/cord-286635-7aflpgxd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-286635-7aflpgxd.txt' === file2bib.sh === id: cord-022262-ck2lhojz author: Gromeier, Matthias title: Genetics, Pathogenesis and Evolution of Picornaviruses date: 2007-09-02 pages: extension: .txt txt: ./txt/cord-022262-ck2lhojz.txt cache: ./cache/cord-022262-ck2lhojz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022262-ck2lhojz.txt' === file2bib.sh === id: cord-281124-4nhy35xn author: Soowannayan, Chumporn title: RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp date: 2011-08-03 pages: extension: .txt txt: ./txt/cord-281124-4nhy35xn.txt cache: ./cache/cord-281124-4nhy35xn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-281124-4nhy35xn.txt' === file2bib.sh === id: cord-268239-neb6xxlf author: Illiano, Anna title: Protein Glycosylation Investigated by Mass Spectrometry: An Overview date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-268239-neb6xxlf.txt cache: ./cache/cord-268239-neb6xxlf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-268239-neb6xxlf.txt' === file2bib.sh === id: cord-279629-t1xjy12y author: Nazneen Akhand, Mst Rubaiat title: Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine date: 2020-04-15 pages: extension: .txt txt: ./txt/cord-279629-t1xjy12y.txt cache: ./cache/cord-279629-t1xjy12y.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279629-t1xjy12y.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66945 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-287450-hydy874v author: Wendt, K Ulrich title: Structures and diseases date: 2008 pages: extension: .txt txt: ./txt/cord-287450-hydy874v.txt cache: ./cache/cord-287450-hydy874v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-287450-hydy874v.txt' === file2bib.sh === id: cord-274293-kzmch37j author: Yang, Li title: Tandem mass tag-based quantitative proteomic analysis of lycorine treatment in highly pathogenic avian influenza H5N1 virus infection date: 2019-10-02 pages: extension: .txt txt: ./txt/cord-274293-kzmch37j.txt cache: ./cache/cord-274293-kzmch37j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274293-kzmch37j.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67192 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66658 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-287266-sd5izamc author: Song, Zhenhui title: EIF4A2 interacts with the membrane protein of transmissible gastroenteritis coronavirus and plays a role in virus replication date: 2019-04-30 pages: extension: .txt txt: ./txt/cord-287266-sd5izamc.txt cache: ./cache/cord-287266-sd5izamc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-287266-sd5izamc.txt' === file2bib.sh === id: cord-271091-ffn59sgf author: Galao, Rui P title: Saccharomyces cerevisiae: a versatile eukaryotic system in virology date: 2007-10-10 pages: extension: .txt txt: ./txt/cord-271091-ffn59sgf.txt cache: ./cache/cord-271091-ffn59sgf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271091-ffn59sgf.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67213 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66966 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-280360-rh37d5wc author: Gibson, David S. title: Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis – Proteomic patterns of joint inflammation in early stage disease date: 2009-05-02 pages: extension: .txt txt: ./txt/cord-280360-rh37d5wc.txt cache: ./cache/cord-280360-rh37d5wc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280360-rh37d5wc.txt' === file2bib.sh === id: cord-284208-8fsqgkw5 author: Zolla, Lello title: Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins date: 2008-11-07 pages: extension: .txt txt: ./txt/cord-284208-8fsqgkw5.txt cache: ./cache/cord-284208-8fsqgkw5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284208-8fsqgkw5.txt' === file2bib.sh === id: cord-283035-tpqf458q author: Thanthrige-Don, Niroshan title: Analyses of the spleen proteome of chickens infected with Marek's disease virus date: 2009-08-01 pages: extension: .txt txt: ./txt/cord-283035-tpqf458q.txt cache: ./cache/cord-283035-tpqf458q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-283035-tpqf458q.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66604 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68031 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-280429-4fota9rl author: Medvedev, Kirill E. title: Functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold date: 2018-06-13 pages: extension: .txt txt: ./txt/cord-280429-4fota9rl.txt cache: ./cache/cord-280429-4fota9rl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-280429-4fota9rl.txt' === file2bib.sh === id: cord-281101-gv1sgbk1 author: Shin, Gu-Choul title: Preparation and characterization of a novel monoclonal antibody specific to severe acute respiratory syndrome-coronavirus nucleocapsid protein date: 2006-08-30 pages: extension: .txt txt: ./txt/cord-281101-gv1sgbk1.txt cache: ./cache/cord-281101-gv1sgbk1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281101-gv1sgbk1.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70419 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68779 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-014685-ihh30q6f author: nan title: Posters P788 - P999 date: 2005-09-21 pages: extension: .txt txt: ./txt/cord-014685-ihh30q6f.txt cache: ./cache/cord-014685-ihh30q6f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-014685-ihh30q6f.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67528 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68076 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 20824 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-285180-32bxx94u author: Lee, Sunhee title: Functional characterization and proteomic analysis of the nucleocapsid protein of porcine deltacoronavirus date: 2015-10-02 pages: extension: .txt txt: ./txt/cord-285180-32bxx94u.txt cache: ./cache/cord-285180-32bxx94u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285180-32bxx94u.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70003 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-277293-eo3bei9x author: Fondong, Vincent N. title: Geminivirus protein structure and function date: 2013-04-25 pages: extension: .txt txt: ./txt/cord-277293-eo3bei9x.txt cache: ./cache/cord-277293-eo3bei9x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-277293-eo3bei9x.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69255 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-262119-s6hc7fxs author: Ostaszewski, Marek title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-262119-s6hc7fxs.txt cache: ./cache/cord-262119-s6hc7fxs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262119-s6hc7fxs.txt' === file2bib.sh === id: cord-282859-uxltqopq author: Rosati, A title: BAG3: a multifaceted protein that regulates major cell pathways date: 2011-04-07 pages: extension: .txt txt: ./txt/cord-282859-uxltqopq.txt cache: ./cache/cord-282859-uxltqopq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-282859-uxltqopq.txt' === file2bib.sh === id: cord-287729-pl88otue author: Gray, Stewart M. title: Plant virus proteins involved in natural vector transmission date: 1996-07-31 pages: extension: .txt txt: ./txt/cord-287729-pl88otue.txt cache: ./cache/cord-287729-pl88otue.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-287729-pl88otue.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70218 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-276988-bvsz5q6d author: Neu, Carolin T. title: Post-Transcriptional Expression Control in Platelet Biogenesis and Function date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-276988-bvsz5q6d.txt cache: ./cache/cord-276988-bvsz5q6d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-276988-bvsz5q6d.txt' === file2bib.sh === id: cord-272268-8vrcwwll author: Kedersha, Nancy title: Chapter 4 Regulation of Translation by Stress Granules and Processing Bodies date: 2009-10-27 pages: extension: .txt txt: ./txt/cord-272268-8vrcwwll.txt cache: ./cache/cord-272268-8vrcwwll.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-272268-8vrcwwll.txt' === file2bib.sh === id: cord-281528-xy8j5jiv author: Di Paola, Luisa title: The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach date: 2020-06-17 pages: extension: .txt txt: ./txt/cord-281528-xy8j5jiv.txt cache: ./cache/cord-281528-xy8j5jiv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-281528-xy8j5jiv.txt' === file2bib.sh === id: cord-290445-vb53bih9 author: Ahmed, Shiek SSJ title: Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery date: 2020-04-23 pages: extension: .txt txt: ./txt/cord-290445-vb53bih9.txt cache: ./cache/cord-290445-vb53bih9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290445-vb53bih9.txt' === file2bib.sh === id: cord-270587-k56fze59 author: Scherbinina, Sofya I. title: Three-Dimensional Structures of Carbohydrates and Where to Find Them date: 2020-10-18 pages: extension: .txt txt: ./txt/cord-270587-k56fze59.txt cache: ./cache/cord-270587-k56fze59.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-270587-k56fze59.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70563 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71004 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-289124-6w2zvvj1 author: Mok, Lawrence title: Proteomic analysis of Pteropus alecto kidney cells in response to the viral mimic, Poly I:C date: 2015-11-02 pages: extension: .txt txt: ./txt/cord-289124-6w2zvvj1.txt cache: ./cache/cord-289124-6w2zvvj1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-289124-6w2zvvj1.txt' === file2bib.sh === id: cord-281552-zfjy3m3i author: Alsaadi, Entedar A. J. title: Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-281552-zfjy3m3i.txt cache: ./cache/cord-281552-zfjy3m3i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-281552-zfjy3m3i.txt' === file2bib.sh === id: cord-279691-v5kpmk0b author: Hagemeijer, Marne C. title: Biogenesis and Dynamics of the Coronavirus Replicative Structures date: 2012-11-21 pages: extension: .txt txt: ./txt/cord-279691-v5kpmk0b.txt cache: ./cache/cord-279691-v5kpmk0b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-279691-v5kpmk0b.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68144 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-286301-7sjw5ci7 author: Sadasivan, Jibin title: Cytoplasmic tail of coronavirus spike protein has intracellular targeting signals date: 2017-04-18 pages: extension: .txt txt: ./txt/cord-286301-7sjw5ci7.txt cache: ./cache/cord-286301-7sjw5ci7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-286301-7sjw5ci7.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72065 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71912 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71614 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72141 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-290638-7ro72sv3 author: Lenstra, Johannes A. title: Antigenicity of the peplomer protein of infectious bronchitis virus date: 1989-01-31 pages: extension: .txt txt: ./txt/cord-290638-7ro72sv3.txt cache: ./cache/cord-290638-7ro72sv3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-290638-7ro72sv3.txt' === file2bib.sh === id: cord-286970-4pl95r0o author: Mamipour, Mina title: An overview on molecular chaperones enhancing solubility of expressed recombinant proteins with correct folding date: 2017-04-12 pages: extension: .txt txt: ./txt/cord-286970-4pl95r0o.txt cache: ./cache/cord-286970-4pl95r0o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-286970-4pl95r0o.txt' === file2bib.sh === id: cord-286217-3uklf2u2 author: Jiang, He-wei title: SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-286217-3uklf2u2.txt cache: ./cache/cord-286217-3uklf2u2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-286217-3uklf2u2.txt' === file2bib.sh === id: cord-287410-boxxlopy author: Devi, Arpita title: In silico designing of multi-epitope vaccine construct against human coronavirus infections date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-287410-boxxlopy.txt cache: ./cache/cord-287410-boxxlopy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-287410-boxxlopy.txt' === file2bib.sh === id: cord-290904-ngvhk0qy author: Zheng, Zhiqiang title: Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2 date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-290904-ngvhk0qy.txt cache: ./cache/cord-290904-ngvhk0qy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290904-ngvhk0qy.txt' === file2bib.sh === id: cord-277424-9aimvogs author: Criscitiello, Michael F. title: Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity date: 2019-11-13 pages: extension: .txt txt: ./txt/cord-277424-9aimvogs.txt cache: ./cache/cord-277424-9aimvogs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-277424-9aimvogs.txt' === file2bib.sh === id: cord-289026-v09m2fzw author: Sun, Yan-gang title: Characterization of the interaction between recombinant porcine aminopeptidase N and spike glycoprotein of porcine epidemic diarrhea virus date: 2018-10-01 pages: extension: .txt txt: ./txt/cord-289026-v09m2fzw.txt cache: ./cache/cord-289026-v09m2fzw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-289026-v09m2fzw.txt' === file2bib.sh === id: cord-285647-9tegcrc3 author: Estrada, Ernesto title: Fractional diffusion on the human proteome as an alternative to the multi-organ damage of SARS-CoV-2 date: 2020-08-17 pages: extension: .txt txt: ./txt/cord-285647-9tegcrc3.txt cache: ./cache/cord-285647-9tegcrc3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285647-9tegcrc3.txt' === file2bib.sh === id: cord-274080-884x48on author: Rumlová, Michaela title: In vitro methods for testing antiviral drugs date: 2018-06-30 pages: extension: .txt txt: ./txt/cord-274080-884x48on.txt cache: ./cache/cord-274080-884x48on.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274080-884x48on.txt' === file2bib.sh === id: cord-289710-ucguzgdm author: nan title: Yeast Kex1p is a Golgi-associated membrane protein: deletions in a cytoplasmic targeting domain result in mislocalization to the vacuolar membrane date: 1992-12-02 pages: extension: .txt txt: ./txt/cord-289710-ucguzgdm.txt cache: ./cache/cord-289710-ucguzgdm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-289710-ucguzgdm.txt' === file2bib.sh === id: cord-286219-qcx5ehnh author: Calistri, Arianna title: The Ubiquitin-Conjugating System: Multiple Roles in Viral Replication and Infection date: 2014-05-06 pages: extension: .txt txt: ./txt/cord-286219-qcx5ehnh.txt cache: ./cache/cord-286219-qcx5ehnh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-286219-qcx5ehnh.txt' === file2bib.sh === id: cord-295381-0dqu3p3y author: Kamal, Adeela title: Therapeutic and diagnostic implications of Hsp90 activation date: 2004-06-01 pages: extension: .txt txt: ./txt/cord-295381-0dqu3p3y.txt cache: ./cache/cord-295381-0dqu3p3y.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-295381-0dqu3p3y.txt' === file2bib.sh === id: cord-290290-wyx9ib7s author: Sinegubova, Maria V. title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-290290-wyx9ib7s.txt cache: ./cache/cord-290290-wyx9ib7s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290290-wyx9ib7s.txt' === file2bib.sh === id: cord-253466-7gpije5d author: Netherton, Christopher title: A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication date: 2007-08-31 pages: extension: .txt txt: ./txt/cord-253466-7gpije5d.txt cache: ./cache/cord-253466-7gpije5d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-253466-7gpije5d.txt' === file2bib.sh === id: cord-268326-sbz3uk5h author: Bonam, Srinivasa Reddy title: Lysosomes as a therapeutic target date: 2019-09-02 pages: extension: .txt txt: ./txt/cord-268326-sbz3uk5h.txt cache: ./cache/cord-268326-sbz3uk5h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-268326-sbz3uk5h.txt' === file2bib.sh === id: cord-287477-aios0h8s author: Sicari, Daria title: Role of the early secretory pathway in SARS-CoV-2 infection date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-287477-aios0h8s.txt cache: ./cache/cord-287477-aios0h8s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-287477-aios0h8s.txt' === file2bib.sh === id: cord-283096-qm7h4qui author: Jeon, Young Joo title: ISG15 and immune diseases date: 2010-02-12 pages: extension: .txt txt: ./txt/cord-283096-qm7h4qui.txt cache: ./cache/cord-283096-qm7h4qui.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-283096-qm7h4qui.txt' === file2bib.sh === id: cord-292985-w62xaa4f author: Römer, Rudolf A. title: Flexibility and mobility of SARS-CoV-2-related protein structures date: 2020-07-12 pages: extension: .txt txt: ./txt/cord-292985-w62xaa4f.txt cache: ./cache/cord-292985-w62xaa4f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292985-w62xaa4f.txt' === file2bib.sh === id: cord-259603-bh198xgl author: Snijder, E.J. title: The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing date: 2016-09-14 pages: extension: .txt txt: ./txt/cord-259603-bh198xgl.txt cache: ./cache/cord-259603-bh198xgl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-259603-bh198xgl.txt' === file2bib.sh === id: cord-292958-k5d5fo3i author: Sekhon, Simranjeet Singh title: Porcine epidemic diarrhea (PED) infection, diagnosis and vaccination: A mini review date: 2017-01-04 pages: extension: .txt txt: ./txt/cord-292958-k5d5fo3i.txt cache: ./cache/cord-292958-k5d5fo3i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292958-k5d5fo3i.txt' === file2bib.sh === id: cord-286603-4p3t0vre author: Duan, Zhiqiang title: TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein date: 2020-06-27 pages: extension: .txt txt: ./txt/cord-286603-4p3t0vre.txt cache: ./cache/cord-286603-4p3t0vre.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-286603-4p3t0vre.txt' === file2bib.sh === id: cord-301128-woe6knpv author: Joyeux, Marc title: Requirements for DNA-bridging proteins to act as topological barriers of the bacterial genome date: 2020-08-12 pages: extension: .txt txt: ./txt/cord-301128-woe6knpv.txt cache: ./cache/cord-301128-woe6knpv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-301128-woe6knpv.txt' === file2bib.sh === id: cord-022955-vy0qgtll author: nan title: Proteases date: 2005-06-20 pages: extension: .txt txt: ./txt/cord-022955-vy0qgtll.txt cache: ./cache/cord-022955-vy0qgtll.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-022955-vy0qgtll.txt' === file2bib.sh === id: cord-304040-64obh7i3 author: Sande, Charles J. title: Untargeted analysis of the airway proteomes of children with respiratory infections using mass spectrometry based proteomics date: 2018-09-14 pages: extension: .txt txt: ./txt/cord-304040-64obh7i3.txt cache: ./cache/cord-304040-64obh7i3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304040-64obh7i3.txt' === file2bib.sh === id: cord-296794-ml2luc1t author: Sollner, Johannes title: Analysis and prediction of protective continuous B-cell epitopes on pathogen proteins date: 2008-01-07 pages: extension: .txt txt: ./txt/cord-296794-ml2luc1t.txt cache: ./cache/cord-296794-ml2luc1t.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-296794-ml2luc1t.txt' === file2bib.sh === id: cord-303494-tofch4j7 author: Bai, Juan title: Identification of VP1 peptides diagnostic of encephalomyocarditis virus from swine date: 2014-12-30 pages: extension: .txt txt: ./txt/cord-303494-tofch4j7.txt cache: ./cache/cord-303494-tofch4j7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303494-tofch4j7.txt' === file2bib.sh === id: cord-267475-6f4h3cck author: Kozak, Marilyn title: Pushing the limits of the scanning mechanism for initiation of translation date: 2002-10-16 pages: extension: .txt txt: ./txt/cord-267475-6f4h3cck.txt cache: ./cache/cord-267475-6f4h3cck.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-267475-6f4h3cck.txt' === file2bib.sh === id: cord-294712-kvvxmvqo author: Pelosse, Martin title: MultiBac: from protein complex structures to synthetic viral nanosystems date: 2017-10-30 pages: extension: .txt txt: ./txt/cord-294712-kvvxmvqo.txt cache: ./cache/cord-294712-kvvxmvqo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294712-kvvxmvqo.txt' === file2bib.sh === id: cord-264996-og3sg0qw author: Howell, Gareth J. title: Cell Biology of Membrane Trafficking in Human Disease date: 2006-09-17 pages: extension: .txt txt: ./txt/cord-264996-og3sg0qw.txt cache: ./cache/cord-264996-og3sg0qw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-264996-og3sg0qw.txt' === file2bib.sh === id: cord-298922-k568hlf4 author: Sun, Dongbo title: Analysis of protein expression changes of the Vero E6 cells infected with classic PEDV strain CV777 by using quantitative proteomic technique date: 2015-06-15 pages: extension: .txt txt: ./txt/cord-298922-k568hlf4.txt cache: ./cache/cord-298922-k568hlf4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298922-k568hlf4.txt' === file2bib.sh === id: cord-016095-jop2rx61 author: Vignais, Pierre V. title: Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century date: 2010-06-08 pages: extension: .txt txt: ./txt/cord-016095-jop2rx61.txt cache: ./cache/cord-016095-jop2rx61.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-016095-jop2rx61.txt' === file2bib.sh === id: cord-298759-j965t808 author: Jiang, Nan title: Development of a robust Escherichia coli-based cell-free protein synthesis application platform date: 2020-10-17 pages: extension: .txt txt: ./txt/cord-298759-j965t808.txt cache: ./cache/cord-298759-j965t808.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298759-j965t808.txt' === file2bib.sh === id: cord-302009-oqc21fah author: Geng, Xindu title: Protein folding liquid chromatography and its recent developments() date: 2007-04-15 pages: extension: .txt txt: ./txt/cord-302009-oqc21fah.txt cache: ./cache/cord-302009-oqc21fah.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-302009-oqc21fah.txt' === file2bib.sh === id: cord-269011-230p8rsf author: de Haan, Cornelis A.M. title: Molecular Interactions in the Assembly of Coronaviruses date: 2005-08-31 pages: extension: .txt txt: ./txt/cord-269011-230p8rsf.txt cache: ./cache/cord-269011-230p8rsf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-269011-230p8rsf.txt' === file2bib.sh === id: cord-305602-yzc4bosn author: Llano, Manuel title: Chapter Seven Defining Pharmacological Targets by Analysis of Virus–Host Protein Interactions date: 2018-12-31 pages: extension: .txt txt: ./txt/cord-305602-yzc4bosn.txt cache: ./cache/cord-305602-yzc4bosn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-305602-yzc4bosn.txt' === file2bib.sh === id: cord-307227-x6xketcn author: Martin, William R. title: Repurposing of FDA-Approved Toremifene to Treat COVID-19 by Blocking the Spike Glycoprotein and NSP14 of SARS-CoV-2 date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-307227-x6xketcn.txt cache: ./cache/cord-307227-x6xketcn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-307227-x6xketcn.txt' === file2bib.sh === id: cord-309043-dlmx12vt author: von Brunn, Albrecht title: Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome date: 2007-05-23 pages: extension: .txt txt: ./txt/cord-309043-dlmx12vt.txt cache: ./cache/cord-309043-dlmx12vt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309043-dlmx12vt.txt' === file2bib.sh === id: cord-292688-w4zvfkyl author: Tooze, Sharon A title: Biogenesis of secretory granules in the trans-Golgi network of neuroendocrine and endocrine cells date: 1998-08-14 pages: extension: .txt txt: ./txt/cord-292688-w4zvfkyl.txt cache: ./cache/cord-292688-w4zvfkyl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292688-w4zvfkyl.txt' === file2bib.sh === id: cord-308641-vqiipbo8 author: Jankauskaitė, Justina title: SKEMPI 2.0: an updated benchmark of changes in protein–protein binding energy, kinetics and thermodynamics upon mutation date: 2019-02-01 pages: extension: .txt txt: ./txt/cord-308641-vqiipbo8.txt cache: ./cache/cord-308641-vqiipbo8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308641-vqiipbo8.txt' === file2bib.sh === id: cord-307811-6e3j0pn7 author: Hao, Wei title: Binding of the SARS-CoV-2 Spike Protein to Glycans date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-307811-6e3j0pn7.txt cache: ./cache/cord-307811-6e3j0pn7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-307811-6e3j0pn7.txt' === file2bib.sh === id: cord-294945-hcf7gsv8 author: Lin, K.H. title: Comparative proteomic analysis of cauliflower under high temperature and flooding stresses date: 2015-02-12 pages: extension: .txt txt: ./txt/cord-294945-hcf7gsv8.txt cache: ./cache/cord-294945-hcf7gsv8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294945-hcf7gsv8.txt' === file2bib.sh === id: cord-288673-ku3tmjd3 author: Sabotič, Jerica title: Microbial and fungal protease inhibitors—current and potential applications date: 2012-01-05 pages: extension: .txt txt: ./txt/cord-288673-ku3tmjd3.txt cache: ./cache/cord-288673-ku3tmjd3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-288673-ku3tmjd3.txt' === file2bib.sh === id: cord-316745-n10ia3j3 author: Liu, HongDe title: A new approach to the prediction of transmembrane structures date: 2008-05-23 pages: extension: .txt txt: ./txt/cord-316745-n10ia3j3.txt cache: ./cache/cord-316745-n10ia3j3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-316745-n10ia3j3.txt' === file2bib.sh === id: cord-302414-g5onwhg1 author: Tahir ul Qamar, Muhammad title: Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2 date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-302414-g5onwhg1.txt cache: ./cache/cord-302414-g5onwhg1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-302414-g5onwhg1.txt' === file2bib.sh === id: cord-305143-mqd4ioj4 author: Zmasek, Christian M. title: Classification of human Herpesviridae proteins using Domain-architecture Aware Inference of Orthologs (DAIO) date: 2019-01-06 pages: extension: .txt txt: ./txt/cord-305143-mqd4ioj4.txt cache: ./cache/cord-305143-mqd4ioj4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-305143-mqd4ioj4.txt' === file2bib.sh === id: cord-295351-0zr2e8lh author: Mohd Ropidi, Muhammad Izzuddin title: Endoplasmic reticulum: a focal point of Zika virus infection date: 2020-01-20 pages: extension: .txt txt: ./txt/cord-295351-0zr2e8lh.txt cache: ./cache/cord-295351-0zr2e8lh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-295351-0zr2e8lh.txt' === file2bib.sh === id: cord-310909-nc82a70n author: Qiu, Maofeng title: Antibody responses to individual proteins of SARS coronavirus and their neutralization activities date: 2005-04-13 pages: extension: .txt txt: ./txt/cord-310909-nc82a70n.txt cache: ./cache/cord-310909-nc82a70n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310909-nc82a70n.txt' === file2bib.sh === id: cord-300796-rmjv56ia author: nan title: The signal sequence of the p62 protein of Semliki Forest virus is involved in initiation but not in completing chain translocation date: 1990-09-01 pages: extension: .txt txt: ./txt/cord-300796-rmjv56ia.txt cache: ./cache/cord-300796-rmjv56ia.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300796-rmjv56ia.txt' === file2bib.sh === id: cord-308043-h0knm8y4 author: Hussey, Séamus title: Autophagy as an emerging dimension to adaptive and innate immunity date: 2009-08-31 pages: extension: .txt txt: ./txt/cord-308043-h0knm8y4.txt cache: ./cache/cord-308043-h0knm8y4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-308043-h0knm8y4.txt' === file2bib.sh === id: cord-306261-yc2y2xak author: van Tricht, Ewoud title: Fast, selective and quantitative protein profiling of adenovirus-vector based vaccines by ultra-performance liquid chromatography date: 2018-12-28 pages: extension: .txt txt: ./txt/cord-306261-yc2y2xak.txt cache: ./cache/cord-306261-yc2y2xak.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306261-yc2y2xak.txt' === file2bib.sh === id: cord-313932-f0a1qh7p author: Chen, Peng title: Establishment and validation of a drug-target microarray for SARS-CoV-2 date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-313932-f0a1qh7p.txt cache: ./cache/cord-313932-f0a1qh7p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-313932-f0a1qh7p.txt' === file2bib.sh === id: cord-304953-ntg8w5k4 author: Modis, Yorgo title: Relating structure to evolution in class II viral membrane fusion proteins date: 2014-02-11 pages: extension: .txt txt: ./txt/cord-304953-ntg8w5k4.txt cache: ./cache/cord-304953-ntg8w5k4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-304953-ntg8w5k4.txt' === file2bib.sh === id: cord-280878-1kt51viz author: To, Janet title: Targeting the Channel Activity of Viroporins date: 2016-01-07 pages: extension: .txt txt: ./txt/cord-280878-1kt51viz.txt cache: ./cache/cord-280878-1kt51viz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-280878-1kt51viz.txt' === file2bib.sh === id: cord-304607-td0776wj author: Paszkiewicz, Konrad H. title: Omics, Bioinformatics, and Infectious Disease Research date: 2010-12-24 pages: extension: .txt txt: ./txt/cord-304607-td0776wj.txt cache: ./cache/cord-304607-td0776wj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304607-td0776wj.txt' === file2bib.sh === id: cord-304616-k92fa15l author: Izes, Aaron M. title: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats date: 2020-08-05 pages: extension: .txt txt: ./txt/cord-304616-k92fa15l.txt cache: ./cache/cord-304616-k92fa15l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-304616-k92fa15l.txt' === file2bib.sh === id: cord-302514-rstvf3mc author: Abbas, Wasim title: The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections date: 2015-04-07 pages: extension: .txt txt: ./txt/cord-302514-rstvf3mc.txt cache: ./cache/cord-302514-rstvf3mc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302514-rstvf3mc.txt' === file2bib.sh === id: cord-315531-2gc2dc46 author: McGarvey, Peter B. title: Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets date: 2009-09-25 pages: extension: .txt txt: ./txt/cord-315531-2gc2dc46.txt cache: ./cache/cord-315531-2gc2dc46.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-315531-2gc2dc46.txt' === file2bib.sh === id: cord-298369-66ifwtlp author: Smith, Sherri A. title: Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein date: 2018-12-28 pages: extension: .txt txt: ./txt/cord-298369-66ifwtlp.txt cache: ./cache/cord-298369-66ifwtlp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-298369-66ifwtlp.txt' === file2bib.sh === id: cord-310947-aqau2n7q author: Pan, Ji'An title: Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication date: 2008-10-01 pages: extension: .txt txt: ./txt/cord-310947-aqau2n7q.txt cache: ./cache/cord-310947-aqau2n7q.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310947-aqau2n7q.txt' === file2bib.sh === id: cord-306733-df36w6l7 author: Rosales-Mendoza, Sergio title: What Does Plant-Based Vaccine Technology Offer to the Fight against COVID-19? date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-306733-df36w6l7.txt cache: ./cache/cord-306733-df36w6l7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-306733-df36w6l7.txt' === file2bib.sh === id: cord-314642-oobbdgzh author: Campbell, Allan title: The future of bacteriophage biology date: 2003 pages: extension: .txt txt: ./txt/cord-314642-oobbdgzh.txt cache: ./cache/cord-314642-oobbdgzh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-314642-oobbdgzh.txt' === file2bib.sh === id: cord-300884-rqfxe0x1 author: Zhang, Jianqiang title: Genomic characterization of equine coronavirus date: 2007-12-05 pages: extension: .txt txt: ./txt/cord-300884-rqfxe0x1.txt cache: ./cache/cord-300884-rqfxe0x1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300884-rqfxe0x1.txt' === file2bib.sh === id: cord-006636-xgikbdns author: Ühlein, E. title: Übersicht Über neue ernährungswissenschaftliche Publikationen date: 1964-02-01 pages: extension: .txt txt: ./txt/cord-006636-xgikbdns.txt cache: ./cache/cord-006636-xgikbdns.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-006636-xgikbdns.txt' === file2bib.sh === id: cord-313988-3xjnpkqp author: Ferraz, Rosa María title: Insertional protein engineering for analytical molecular sensing date: 2006-04-03 pages: extension: .txt txt: ./txt/cord-313988-3xjnpkqp.txt cache: ./cache/cord-313988-3xjnpkqp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-313988-3xjnpkqp.txt' === file2bib.sh === id: cord-312489-ywep0c08 author: Andoh, Kiyohiko title: Decreased neutralizing antigenicity in IBV S1 protein expressed from mammalian cells date: 2015-10-02 pages: extension: .txt txt: ./txt/cord-312489-ywep0c08.txt cache: ./cache/cord-312489-ywep0c08.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312489-ywep0c08.txt' === file2bib.sh === id: cord-298251-u36lb44w author: Donaldson, Julie G. title: Arf Family G Proteins and their regulators: roles in membrane transport, development and disease date: 2011-05-18 pages: extension: .txt txt: ./txt/cord-298251-u36lb44w.txt cache: ./cache/cord-298251-u36lb44w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-298251-u36lb44w.txt' === file2bib.sh === id: cord-306111-wn1gxhk9 author: Dommett, R. M. title: Mannose‐binding lectin in innate immunity: past, present and future date: 2006-09-01 pages: extension: .txt txt: ./txt/cord-306111-wn1gxhk9.txt cache: ./cache/cord-306111-wn1gxhk9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-306111-wn1gxhk9.txt' === file2bib.sh === id: cord-310680-klywz85w author: Li, Qihan title: The interaction of the SARS coronavirus non-structural protein 10 with the cellular oxido-reductase system causes an extensive cytopathic effect date: 2005-04-06 pages: extension: .txt txt: ./txt/cord-310680-klywz85w.txt cache: ./cache/cord-310680-klywz85w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-310680-klywz85w.txt' === file2bib.sh === id: cord-303555-mwu72q7w author: Dent, Paul title: Cell Signaling and Translational Developmental Therapeutics date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-303555-mwu72q7w.txt cache: ./cache/cord-303555-mwu72q7w.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-303555-mwu72q7w.txt' === file2bib.sh === id: cord-300418-s4wt5gim author: Bedford, Lynn title: Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets date: 2010-12-10 pages: extension: .txt txt: ./txt/cord-300418-s4wt5gim.txt cache: ./cache/cord-300418-s4wt5gim.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-300418-s4wt5gim.txt' === file2bib.sh === id: cord-312996-qzu8pkyt author: Iles, R. K. title: A clinical MALDI-ToF Mass spectrometry assay for SARS-CoV-2: Rational design and multi-disciplinary team work. date: 2020-08-22 pages: extension: .txt txt: ./txt/cord-312996-qzu8pkyt.txt cache: ./cache/cord-312996-qzu8pkyt.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-312996-qzu8pkyt.txt' === file2bib.sh === id: cord-306624-1mjmttec author: Wodrich, Harald title: A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry date: 2010-03-19 pages: extension: .txt txt: ./txt/cord-306624-1mjmttec.txt cache: ./cache/cord-306624-1mjmttec.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-306624-1mjmttec.txt' === file2bib.sh === id: cord-304306-rxjahqwh author: Vlachakis, Dimitrios title: Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-304306-rxjahqwh.txt cache: ./cache/cord-304306-rxjahqwh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-304306-rxjahqwh.txt' === file2bib.sh === id: cord-315984-5gbhobw8 author: Isaacson, Marisa K. title: Ubiquitination, Ubiquitin-like Modifiers, and Deubiquitination in Viral Infection date: 2009-06-18 pages: extension: .txt txt: ./txt/cord-315984-5gbhobw8.txt cache: ./cache/cord-315984-5gbhobw8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315984-5gbhobw8.txt' === file2bib.sh === id: cord-314751-i9rxesrg author: Oh, Jongsuk title: Immunogenicity and protective efficacy of recombinant S1 domain of the porcine epidemic diarrhea virus spike protein date: 2014-07-10 pages: extension: .txt txt: ./txt/cord-314751-i9rxesrg.txt cache: ./cache/cord-314751-i9rxesrg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-314751-i9rxesrg.txt' === file2bib.sh === id: cord-314039-qkrmxvaj author: Houdebine, Louis-Marie title: Production of pharmaceutical proteins by transgenic animals date: 2008-02-19 pages: extension: .txt txt: ./txt/cord-314039-qkrmxvaj.txt cache: ./cache/cord-314039-qkrmxvaj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-314039-qkrmxvaj.txt' === file2bib.sh === id: cord-314746-1o0rf0ii author: Bergasa-Caceres, Fernando title: Interdiction of Protein Folding for Therapeutic Drug Development in SARS CoV-2 date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-314746-1o0rf0ii.txt cache: ./cache/cord-314746-1o0rf0ii.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314746-1o0rf0ii.txt' === file2bib.sh === id: cord-319517-denczc6t author: Salipalli, Sandeep title: Recent advances in live cell imaging of hepatoma cells date: 2014-07-08 pages: extension: .txt txt: ./txt/cord-319517-denczc6t.txt cache: ./cache/cord-319517-denczc6t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319517-denczc6t.txt' === file2bib.sh === id: cord-318749-k91oku7h author: Dong, Hui-Jun title: Selective regulation in ribosome biogenesis and protein production for efficient viral translation date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-318749-k91oku7h.txt cache: ./cache/cord-318749-k91oku7h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-318749-k91oku7h.txt' === file2bib.sh === id: cord-319609-y0gdjn64 author: Van Duyne, Rachel title: The identification of unique serum proteins of HIV-1 latently infected long-term non-progressor patients date: 2010-07-06 pages: extension: .txt txt: ./txt/cord-319609-y0gdjn64.txt cache: ./cache/cord-319609-y0gdjn64.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319609-y0gdjn64.txt' === file2bib.sh === id: cord-312332-rwmuucsp author: Dicker, Kate title: The importance of virion-incorporated cellular RNA-Binding Proteins in viral particle assembly and infectivity date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-312332-rwmuucsp.txt cache: ./cache/cord-312332-rwmuucsp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-312332-rwmuucsp.txt' === file2bib.sh === id: cord-314321-klb8oe9q author: Chen, Serena H. title: Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets date: 2020-04-18 pages: extension: .txt txt: ./txt/cord-314321-klb8oe9q.txt cache: ./cache/cord-314321-klb8oe9q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314321-klb8oe9q.txt' === file2bib.sh === id: cord-023143-fcno330z author: nan title: Molecular aspects of viral immunity date: 2004-02-19 pages: extension: .txt txt: ./txt/cord-023143-fcno330z.txt cache: ./cache/cord-023143-fcno330z.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 5 resourceName b'cord-023143-fcno330z.txt' === file2bib.sh === id: cord-316258-7hucqcaj author: Henriques, Elsa S title: Modeling of the Toll-like receptor 3 and a putative Toll-like receptor 3 antagonist encoded by the African swine fever virus date: 2011-01-28 pages: extension: .txt txt: ./txt/cord-316258-7hucqcaj.txt cache: ./cache/cord-316258-7hucqcaj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-316258-7hucqcaj.txt' === file2bib.sh === id: cord-320083-0k15w624 author: Leitão, Jorge H. title: Microbial Virulence Factors date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-320083-0k15w624.txt cache: ./cache/cord-320083-0k15w624.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-320083-0k15w624.txt' === file2bib.sh === id: cord-318853-mxyxwkhx author: Sallie, Richard title: Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases date: 2005-08-22 pages: extension: .txt txt: ./txt/cord-318853-mxyxwkhx.txt cache: ./cache/cord-318853-mxyxwkhx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318853-mxyxwkhx.txt' === file2bib.sh === id: cord-307731-a2fqmaly author: Vázquez, Javier title: Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-307731-a2fqmaly.txt cache: ./cache/cord-307731-a2fqmaly.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-307731-a2fqmaly.txt' === file2bib.sh === id: cord-321275-7haq0e38 author: Renzi, Fabiana title: Large-scale purification and crystallization of the endoribonuclease XendoU: troubleshooting with His-tagged proteins date: 2006-02-28 pages: extension: .txt txt: ./txt/cord-321275-7haq0e38.txt cache: ./cache/cord-321275-7haq0e38.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321275-7haq0e38.txt' === file2bib.sh === id: cord-324325-rmlrhyf2 author: Chan, Wai S title: Coronaviral hypothetical and structural proteins were found in the intestinal surface enterocytes and pneumocytes of severe acute respiratory syndrome (SARS) date: 2005-05-13 pages: extension: .txt txt: ./txt/cord-324325-rmlrhyf2.txt cache: ./cache/cord-324325-rmlrhyf2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324325-rmlrhyf2.txt' === file2bib.sh === id: cord-300429-b0zev8zb author: Sobocińska, Justyna title: Protein Palmitoylation and Its Role in Bacterial and Viral Infections date: 2018-01-19 pages: extension: .txt txt: ./txt/cord-300429-b0zev8zb.txt cache: ./cache/cord-300429-b0zev8zb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300429-b0zev8zb.txt' === file2bib.sh === id: cord-319884-d8n0aokl author: Natesan, Mohan title: Protein Microarrays and Biomarkers of Infectious Disease date: 2010-12-16 pages: extension: .txt txt: ./txt/cord-319884-d8n0aokl.txt cache: ./cache/cord-319884-d8n0aokl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-319884-d8n0aokl.txt' === file2bib.sh === id: cord-323072-4rsgeag7 author: Han, Xueqing title: The expression of SARS–CoV M gene in P. Pastoris and the diagnostic utility of the expression product date: 2004-12-01 pages: extension: .txt txt: ./txt/cord-323072-4rsgeag7.txt cache: ./cache/cord-323072-4rsgeag7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-323072-4rsgeag7.txt' === file2bib.sh === id: cord-322926-xlwsj3v2 author: Shanmugaraj, Balamurugan title: Plant Molecular Farming: A Viable Platform for Recombinant Biopharmaceutical Production date: 2020-07-04 pages: extension: .txt txt: ./txt/cord-322926-xlwsj3v2.txt cache: ./cache/cord-322926-xlwsj3v2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322926-xlwsj3v2.txt' === file2bib.sh === id: cord-314567-purplsjn author: Fernández-Ponce, Cecilia title: Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells date: 2018-01-04 pages: extension: .txt txt: ./txt/cord-314567-purplsjn.txt cache: ./cache/cord-314567-purplsjn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-314567-purplsjn.txt' === file2bib.sh === id: cord-321386-u1imic5l author: Li, Chun title: Protein Sequence Comparison and DNA-binding Protein Identification with Generalized PseAAC and Graphical Representation date: 2018-02-17 pages: extension: .txt txt: ./txt/cord-321386-u1imic5l.txt cache: ./cache/cord-321386-u1imic5l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-321386-u1imic5l.txt' === file2bib.sh === id: cord-316983-h4mtpcyc author: Mathé-Hubert, Hugo title: Comparative venomics of Psyttalia lounsburyi and P. concolor, two olive fruit fly parasitoids: a hypothetical role for a GH1 β-glucosidase date: 2016-10-25 pages: extension: .txt txt: ./txt/cord-316983-h4mtpcyc.txt cache: ./cache/cord-316983-h4mtpcyc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316983-h4mtpcyc.txt' === file2bib.sh === id: cord-318551-c1qr27lg author: Boguszewska‐Chachulska, Anna M. title: Rna Viruses Redirect Host Factors to Better Amplify Their Genome date: 2005-12-29 pages: extension: .txt txt: ./txt/cord-318551-c1qr27lg.txt cache: ./cache/cord-318551-c1qr27lg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-318551-c1qr27lg.txt' === file2bib.sh === id: cord-319614-4qi59pbz author: Benej, Martin title: Quantitative Proteomics Reveal Peroxiredoxin Perturbation Upon Persistent Lymphocytic Choriomeningitis Virus Infection in Human Cells date: 2019-10-25 pages: extension: .txt txt: ./txt/cord-319614-4qi59pbz.txt cache: ./cache/cord-319614-4qi59pbz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-319614-4qi59pbz.txt' === file2bib.sh === id: cord-326015-ky4y2xjt author: Füllekrug, Joachim title: Protein sorting in the Golgi complex date: 1998-08-14 pages: extension: .txt txt: ./txt/cord-326015-ky4y2xjt.txt cache: ./cache/cord-326015-ky4y2xjt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-326015-ky4y2xjt.txt' === file2bib.sh === id: cord-322231-jltk42dt author: Huy, Nguyen-Xuan title: Immunogenicity of an S1D epitope from porcine epidemic diarrhea virus and cholera toxin B subunit fusion protein transiently expressed in infiltrated Nicotiana benthamiana leaves date: 2016-08-23 pages: extension: .txt txt: ./txt/cord-322231-jltk42dt.txt cache: ./cache/cord-322231-jltk42dt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322231-jltk42dt.txt' === file2bib.sh === id: cord-319809-33i6lzjd author: Drew, Elliot D. title: Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-319809-33i6lzjd.txt cache: ./cache/cord-319809-33i6lzjd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319809-33i6lzjd.txt' === file2bib.sh === id: cord-319658-u0wjgw50 author: Guven-Maiorov, Emine title: Structural host-microbiota interaction networks date: 2017-10-12 pages: extension: .txt txt: ./txt/cord-319658-u0wjgw50.txt cache: ./cache/cord-319658-u0wjgw50.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-319658-u0wjgw50.txt' === file2bib.sh === id: cord-320092-0qnvydux author: Ehsani, Sepehr title: COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-320092-0qnvydux.txt cache: ./cache/cord-320092-0qnvydux.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-320092-0qnvydux.txt' === file2bib.sh === id: cord-313694-p2sgaypq author: West, Christopher M. title: Current ideas on the significance of protein glycosylation date: 1986 pages: extension: .txt txt: ./txt/cord-313694-p2sgaypq.txt cache: ./cache/cord-313694-p2sgaypq.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-313694-p2sgaypq.txt' === file2bib.sh === id: cord-323768-r7jbm1et author: Lagarda-Diaz, Irlanda title: Legume Lectins: Proteins with Diverse Applications date: 2017-06-12 pages: extension: .txt txt: ./txt/cord-323768-r7jbm1et.txt cache: ./cache/cord-323768-r7jbm1et.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323768-r7jbm1et.txt' === file2bib.sh === id: cord-332317-wrztpeb8 author: Zhang, Xin title: Identification of the interaction between vimentin and nucleocapsid protein of transmissible gastroenteritis virus date: 2015-03-16 pages: extension: .txt txt: ./txt/cord-332317-wrztpeb8.txt cache: ./cache/cord-332317-wrztpeb8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332317-wrztpeb8.txt' === file2bib.sh === id: cord-310847-63gh2tg4 author: Uversky, Vladimir N title: The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins date: 2013-04-01 pages: extension: .txt txt: ./txt/cord-310847-63gh2tg4.txt cache: ./cache/cord-310847-63gh2tg4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310847-63gh2tg4.txt' === file2bib.sh === id: cord-325043-vqjhiv7p author: Gorbalenya, Alexander E. title: An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication date: 1989 pages: extension: .txt txt: ./txt/cord-325043-vqjhiv7p.txt cache: ./cache/cord-325043-vqjhiv7p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325043-vqjhiv7p.txt' === file2bib.sh === id: cord-317675-s1ac5vcx author: de Marco, Ario title: Strategies for successful recombinant expression of disulfide bond-dependent proteins in Escherichia coli date: 2009-05-14 pages: extension: .txt txt: ./txt/cord-317675-s1ac5vcx.txt cache: ./cache/cord-317675-s1ac5vcx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-317675-s1ac5vcx.txt' === file2bib.sh === id: cord-312741-0au4nctt author: Lin, Panpan title: Coronavirus in human diseases: Mechanisms and advances in clinical treatment date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-312741-0au4nctt.txt cache: ./cache/cord-312741-0au4nctt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312741-0au4nctt.txt' === file2bib.sh === id: cord-332811-kjgah8ts author: Lee, Do Hyun title: Immunoprophylactic effect of chicken egg yolk antibody (IgY) against a recombinant S1 domain of the porcine epidemic diarrhea virus spike protein in piglets date: 2015-06-23 pages: extension: .txt txt: ./txt/cord-332811-kjgah8ts.txt cache: ./cache/cord-332811-kjgah8ts.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-332811-kjgah8ts.txt' === file2bib.sh === id: cord-320015-lbr2q4qh author: Chinchar, V. Gregory title: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date: 2011-10-20 pages: extension: .txt txt: ./txt/cord-320015-lbr2q4qh.txt cache: ./cache/cord-320015-lbr2q4qh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320015-lbr2q4qh.txt' === file2bib.sh === id: cord-332344-upsn0zb4 author: Jeswin, Joseph title: Proteomic analysis by iTRAQ in red claw crayfish, Cherax quadricarinatus, hematopoietic tissue cells post white spot syndrome virus infection date: 2016-02-01 pages: extension: .txt txt: ./txt/cord-332344-upsn0zb4.txt cache: ./cache/cord-332344-upsn0zb4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-332344-upsn0zb4.txt' === file2bib.sh === id: cord-329625-hx2rsi91 author: You, Jae-Hwan title: A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging date: 2008-08-15 pages: extension: .txt txt: ./txt/cord-329625-hx2rsi91.txt cache: ./cache/cord-329625-hx2rsi91.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-329625-hx2rsi91.txt' === file2bib.sh === id: cord-302490-em1tiz7s author: Cañadas, Olga title: Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis date: 2020-05-25 pages: extension: .txt txt: ./txt/cord-302490-em1tiz7s.txt cache: ./cache/cord-302490-em1tiz7s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302490-em1tiz7s.txt' === file2bib.sh === id: cord-332948-h297ukuu author: Olotu, Fisayo A. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-332948-h297ukuu.txt cache: ./cache/cord-332948-h297ukuu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-332948-h297ukuu.txt' === file2bib.sh === id: cord-319563-9lwr6k8p author: Aitekenov, Sultan title: Review: Detection and quantification of proteins in human urine date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-319563-9lwr6k8p.txt cache: ./cache/cord-319563-9lwr6k8p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-319563-9lwr6k8p.txt' === file2bib.sh === id: cord-330715-olypwdoq author: Sun, Zeyu title: Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications date: 2020-08-30 pages: extension: .txt txt: ./txt/cord-330715-olypwdoq.txt cache: ./cache/cord-330715-olypwdoq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330715-olypwdoq.txt' === file2bib.sh === id: cord-319291-6l688krc author: Hung, Chun-Min title: Alignment using genetic programming with causal trees for identification of protein functions date: 2006-09-01 pages: extension: .txt txt: ./txt/cord-319291-6l688krc.txt cache: ./cache/cord-319291-6l688krc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319291-6l688krc.txt' === file2bib.sh === id: cord-327199-ggomuomb author: Moerdyk-Schauwecker, Megan title: Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions date: 2014-08-08 pages: extension: .txt txt: ./txt/cord-327199-ggomuomb.txt cache: ./cache/cord-327199-ggomuomb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-327199-ggomuomb.txt' === file2bib.sh === id: cord-315570-khm1veuv author: González-Mora, Alejandro title: Bacteriophage-Based Vaccines: A Potent Approach for Antigen Delivery date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-315570-khm1veuv.txt cache: ./cache/cord-315570-khm1veuv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-315570-khm1veuv.txt' === file2bib.sh === id: cord-320790-ley91488 author: Fogg, M. J. title: Application of the use of high‐throughput technologies to the determination of protein structures of bacterial and viral pathogens date: 2006-10-04 pages: extension: .txt txt: ./txt/cord-320790-ley91488.txt cache: ./cache/cord-320790-ley91488.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-320790-ley91488.txt' === file2bib.sh === id: cord-329840-f3dsu36p author: Hati, Sanchita title: Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-329840-f3dsu36p.txt cache: ./cache/cord-329840-f3dsu36p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329840-f3dsu36p.txt' === file2bib.sh === id: cord-321441-t1v0pu0w author: Yang, Yiming title: Polycistronic Genome Segment Evolution and Gain and Loss of FAST Protein Function during Fusogenic Orthoreovirus Speciation date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-321441-t1v0pu0w.txt cache: ./cache/cord-321441-t1v0pu0w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-321441-t1v0pu0w.txt' === file2bib.sh === id: cord-330337-d41imvo7 author: Basu, Souradip title: Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-330337-d41imvo7.txt cache: ./cache/cord-330337-d41imvo7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-330337-d41imvo7.txt' === file2bib.sh === id: cord-014597-66vd2mdu author: nan title: Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017 date: 2018-03-15 pages: extension: .txt txt: ./txt/cord-014597-66vd2mdu.txt cache: ./cache/cord-014597-66vd2mdu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-014597-66vd2mdu.txt' === file2bib.sh === id: cord-323358-05bk91lm author: Bhaskar, Sathyamoorthy title: Engineering protein nanocages as carriers for biomedical applications date: 2017-04-07 pages: extension: .txt txt: ./txt/cord-323358-05bk91lm.txt cache: ./cache/cord-323358-05bk91lm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-323358-05bk91lm.txt' === file2bib.sh === id: cord-325282-20l9xcmg author: Helal, Mohamed A. title: Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-325282-20l9xcmg.txt cache: ./cache/cord-325282-20l9xcmg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325282-20l9xcmg.txt' === file2bib.sh === id: cord-321762-7kiahjyy author: Nandy, Ashesh title: Chapter 5 The GRANCH Techniques for Analysis of DNA, RNA and Protein Sequences date: 2015-12-31 pages: extension: .txt txt: ./txt/cord-321762-7kiahjyy.txt cache: ./cache/cord-321762-7kiahjyy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-321762-7kiahjyy.txt' === file2bib.sh === id: cord-306904-8iteddug author: Uversky, Vladimir N title: Unreported intrinsic disorder in proteins: Building connections to the literature on IDPs date: 2014-12-12 pages: extension: .txt txt: ./txt/cord-306904-8iteddug.txt cache: ./cache/cord-306904-8iteddug.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306904-8iteddug.txt' === file2bib.sh === id: cord-309384-vlk8cebh author: Kolter, Thomas title: Ganglioside Biochemistry date: 2012-12-19 pages: extension: .txt txt: ./txt/cord-309384-vlk8cebh.txt cache: ./cache/cord-309384-vlk8cebh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309384-vlk8cebh.txt' === file2bib.sh === id: cord-337032-s4g4g80w author: Gupta, Manoj Kumar title: In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel date: 2020-04-15 pages: extension: .txt txt: ./txt/cord-337032-s4g4g80w.txt cache: ./cache/cord-337032-s4g4g80w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337032-s4g4g80w.txt' === file2bib.sh === id: cord-328003-yovp8squ author: Duan, Liangwei title: The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-328003-yovp8squ.txt cache: ./cache/cord-328003-yovp8squ.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328003-yovp8squ.txt' === file2bib.sh === id: cord-325943-3hvy7b7c author: Bouwman, Kim M. title: Guinea Fowl Coronavirus Diversity Has Phenotypic Consequences for Glycan and Tissue Binding date: 2019-05-01 pages: extension: .txt txt: ./txt/cord-325943-3hvy7b7c.txt cache: ./cache/cord-325943-3hvy7b7c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325943-3hvy7b7c.txt' === file2bib.sh === id: cord-319754-5isw53wl author: Balgoma, David title: Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update date: 2020-08-31 pages: extension: .txt txt: ./txt/cord-319754-5isw53wl.txt cache: ./cache/cord-319754-5isw53wl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-319754-5isw53wl.txt' === file2bib.sh === id: cord-324667-wmhdw1qs author: Nishtala, Krishnatej title: Tear biomarkers for keratoconus date: 2016-08-04 pages: extension: .txt txt: ./txt/cord-324667-wmhdw1qs.txt cache: ./cache/cord-324667-wmhdw1qs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324667-wmhdw1qs.txt' === file2bib.sh === id: cord-321013-8pkrg0mx author: McBride, Ruth title: The Coronavirus Nucleocapsid Is a Multifunctional Protein date: 2014-08-07 pages: extension: .txt txt: ./txt/cord-321013-8pkrg0mx.txt cache: ./cache/cord-321013-8pkrg0mx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-321013-8pkrg0mx.txt' === file2bib.sh === id: cord-301827-a7hnuxy5 author: Uversky, Vladimir N title: A decade and a half of protein intrinsic disorder: Biology still waits for physics date: 2013-04-29 pages: extension: .txt txt: ./txt/cord-301827-a7hnuxy5.txt cache: ./cache/cord-301827-a7hnuxy5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-301827-a7hnuxy5.txt' === file2bib.sh === id: cord-304343-m7tbdfri author: Khandia, Rekha title: A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy date: 2019-07-03 pages: extension: .txt txt: ./txt/cord-304343-m7tbdfri.txt cache: ./cache/cord-304343-m7tbdfri.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-304343-m7tbdfri.txt' === file2bib.sh === id: cord-330475-mameyzih author: Shi, Da title: Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus date: 2014-03-13 pages: extension: .txt txt: ./txt/cord-330475-mameyzih.txt cache: ./cache/cord-330475-mameyzih.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330475-mameyzih.txt' === file2bib.sh === id: cord-327000-oyg3oyx1 author: Li, Shasha title: Porcine Epidemic Diarrhea Virus and the Host Innate Immune Response date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-327000-oyg3oyx1.txt cache: ./cache/cord-327000-oyg3oyx1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-327000-oyg3oyx1.txt' === file2bib.sh === id: cord-319722-udqu5jub author: Ng, Eddy W. Y. title: Advances in MALDI Mass Spectrometry in Clinical Diagnostic Applications date: 2013-04-07 pages: extension: .txt txt: ./txt/cord-319722-udqu5jub.txt cache: ./cache/cord-319722-udqu5jub.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-319722-udqu5jub.txt' === file2bib.sh === id: cord-329493-ueqlhgn0 author: Stadler, Konrad title: SARS — beginning to understand a new virus date: 2003 pages: extension: .txt txt: ./txt/cord-329493-ueqlhgn0.txt cache: ./cache/cord-329493-ueqlhgn0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-329493-ueqlhgn0.txt' === file2bib.sh === id: cord-327744-5k8np850 author: Munteanu, Cristian Robert title: Multi-target QPDR classification model for human breast and colon cancer-related proteins using star graph topological indices date: 2009-03-21 pages: extension: .txt txt: ./txt/cord-327744-5k8np850.txt cache: ./cache/cord-327744-5k8np850.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-327744-5k8np850.txt' === file2bib.sh === id: cord-327934-hjimlb6i author: Acar, Delphine D. title: Identification of peptide domains involved in the subcellular localization of the feline coronavirus 3b protein date: 2019-10-01 pages: extension: .txt txt: ./txt/cord-327934-hjimlb6i.txt cache: ./cache/cord-327934-hjimlb6i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-327934-hjimlb6i.txt' === file2bib.sh === id: cord-325559-di8lljoi author: Cappello, Francesco title: Does SARS-CoV-2 Trigger Stress-Induced Autoimmunity by Molecular Mimicry? A Hypothesis date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-325559-di8lljoi.txt cache: ./cache/cord-325559-di8lljoi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-325559-di8lljoi.txt' === file2bib.sh === id: cord-330668-7aw17jf8 author: Chen, Cheng-Chang title: ORF8a of SARS-CoV forms an ion channel: Experiments and molecular dynamics simulations date: 2011-02-28 pages: extension: .txt txt: ./txt/cord-330668-7aw17jf8.txt cache: ./cache/cord-330668-7aw17jf8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-330668-7aw17jf8.txt' === file2bib.sh === id: cord-328046-5us4se5o author: Xu, H. Y. title: Further Identification and Characterization of Novel Intermediate and Mature Cleavage Products Released from the ORF 1b Region of the Avian Coronavirus Infectious Bronchitis Virus 1a/1b Polyprotein date: 2001-09-30 pages: extension: .txt txt: ./txt/cord-328046-5us4se5o.txt cache: ./cache/cord-328046-5us4se5o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-328046-5us4se5o.txt' === file2bib.sh === id: cord-329403-jzrlywfe author: Teo, Su Hui Catherine title: A NS1-binding monoclonal antibody interacts with two residues that are highly conserved in seasonal as well as newly emerged influenza A virus date: 2019-03-06 pages: extension: .txt txt: ./txt/cord-329403-jzrlywfe.txt cache: ./cache/cord-329403-jzrlywfe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329403-jzrlywfe.txt' === file2bib.sh === id: cord-332784-xkc89uaz author: Mishra, Shashank Shekhar title: Computational investigation of potential inhibitors of novel coronavirus 2019 through structure-based virtual screening, molecular dynamics and density functional theory studies date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-332784-xkc89uaz.txt cache: ./cache/cord-332784-xkc89uaz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-332784-xkc89uaz.txt' === file2bib.sh === id: cord-346819-11fkgzaa author: Khan, Mohd Imran title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-346819-11fkgzaa.txt cache: ./cache/cord-346819-11fkgzaa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-346819-11fkgzaa.txt' === file2bib.sh === id: cord-338980-pygykil7 author: Rahaman, Jordon title: Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses date: 2016-11-09 pages: extension: .txt txt: ./txt/cord-338980-pygykil7.txt cache: ./cache/cord-338980-pygykil7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-338980-pygykil7.txt' === file2bib.sh === id: cord-333966-st6gyozv author: Taherkhani, Reza title: Design and production of a multiepitope construct derived from hepatitis E virus capsid protein date: 2015-03-17 pages: extension: .txt txt: ./txt/cord-333966-st6gyozv.txt cache: ./cache/cord-333966-st6gyozv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333966-st6gyozv.txt' === file2bib.sh === id: cord-338485-4zqeq1se author: Aiking, Harry title: The next protein transition() date: 2018-07-27 pages: extension: .txt txt: ./txt/cord-338485-4zqeq1se.txt cache: ./cache/cord-338485-4zqeq1se.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338485-4zqeq1se.txt' === file2bib.sh === id: cord-339333-7tpnbr8q author: CHEN, YUXIAN title: Comparative serum proteome expression of the steroid-induced femoral head osteonecrosis in adults date: 2014-11-12 pages: extension: .txt txt: ./txt/cord-339333-7tpnbr8q.txt cache: ./cache/cord-339333-7tpnbr8q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-339333-7tpnbr8q.txt' === file2bib.sh === id: cord-325230-3kg4oe4g author: Agol, Vadim I. title: Viral security proteins: counteracting host defences date: 2010-11-09 pages: extension: .txt txt: ./txt/cord-325230-3kg4oe4g.txt cache: ./cache/cord-325230-3kg4oe4g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325230-3kg4oe4g.txt' === file2bib.sh === id: cord-284648-yznlgzir author: Varanko, Anastasia title: Recent trends in protein and peptide-based biomaterials for advanced drug delivery date: 2020-08-29 pages: extension: .txt txt: ./txt/cord-284648-yznlgzir.txt cache: ./cache/cord-284648-yznlgzir.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-284648-yznlgzir.txt' === file2bib.sh === id: cord-324640-2zhaknbi author: Munday, Diane C. title: Quantitative Proteomic Analysis of A549 Cells Infected with Human Respiratory Syncytial Virus date: 2010-07-20 pages: extension: .txt txt: ./txt/cord-324640-2zhaknbi.txt cache: ./cache/cord-324640-2zhaknbi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-324640-2zhaknbi.txt' === file2bib.sh === id: cord-322955-7dw32xby author: Kathwate, Gunderao H title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-322955-7dw32xby.txt cache: ./cache/cord-322955-7dw32xby.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322955-7dw32xby.txt' === file2bib.sh === id: cord-342639-vf9n2vf9 author: Chang, Chung-ke title: Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging date: 2013-05-23 pages: extension: .txt txt: ./txt/cord-342639-vf9n2vf9.txt cache: ./cache/cord-342639-vf9n2vf9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342639-vf9n2vf9.txt' === file2bib.sh === id: cord-319780-rfj9t99r author: Alexander, S.P.H. title: A rational roadmap for SARS‐CoV‐2/COVID‐19 pharmacotherapeutic research and development. IUPHAR Review 29 date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-319780-rfj9t99r.txt cache: ./cache/cord-319780-rfj9t99r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-319780-rfj9t99r.txt' === file2bib.sh === id: cord-316273-vo6j8zb0 author: Cosset, François-Loic title: Cell Entry of Enveloped Viruses date: 2011-02-08 pages: extension: .txt txt: ./txt/cord-316273-vo6j8zb0.txt cache: ./cache/cord-316273-vo6j8zb0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316273-vo6j8zb0.txt' === file2bib.sh === id: cord-325825-0lyt8gfq author: Griffiths, Samantha J. title: A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date: 2013-08-08 pages: extension: .txt txt: ./txt/cord-325825-0lyt8gfq.txt cache: ./cache/cord-325825-0lyt8gfq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325825-0lyt8gfq.txt' === file2bib.sh === id: cord-350309-j4oh1z8m author: Liu, D. X. title: Coronavirus envelope protein: A small membrane protein with multiple functions date: 2007-05-29 pages: extension: .txt txt: ./txt/cord-350309-j4oh1z8m.txt cache: ./cache/cord-350309-j4oh1z8m.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-350309-j4oh1z8m.txt' === file2bib.sh === id: cord-333309-21czobqy author: Byun, Hyewon title: ERAD and how viruses exploit it date: 2014-07-03 pages: extension: .txt txt: ./txt/cord-333309-21czobqy.txt cache: ./cache/cord-333309-21czobqy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-333309-21czobqy.txt' === file2bib.sh === id: cord-335915-2apj4qy9 author: Melillo, Alessandro title: Applications of Serum Protein Electrophoresis in Exotic Pet Medicine date: 2013-01-22 pages: extension: .txt txt: ./txt/cord-335915-2apj4qy9.txt cache: ./cache/cord-335915-2apj4qy9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-335915-2apj4qy9.txt' === file2bib.sh === id: cord-341378-pw60qx7c author: Armstrong, John title: Sequence and topology of a model intracellular membrane protein, E1 glycoprotein, from a coronavirus date: 1984 pages: extension: .txt txt: ./txt/cord-341378-pw60qx7c.txt cache: ./cache/cord-341378-pw60qx7c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341378-pw60qx7c.txt' === file2bib.sh === id: cord-340746-icuzy3vp author: Liang, Yunfei title: Comprehensive Antibody Epitope Mapping of the Nucleocapsid Protein of Severe Acute Respiratory Syndrome (SARS) Coronavirus: Insight into the Humoral Immunity of SARS date: 2005-08-01 pages: extension: .txt txt: ./txt/cord-340746-icuzy3vp.txt cache: ./cache/cord-340746-icuzy3vp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-340746-icuzy3vp.txt' === file2bib.sh === id: cord-333089-ufyzqgqk author: Aguilar-Pineda, Jorge Alberto title: Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-333089-ufyzqgqk.txt cache: ./cache/cord-333089-ufyzqgqk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333089-ufyzqgqk.txt' === file2bib.sh === id: cord-328483-sj8i9ss2 author: Jaegle, Mike title: Protein‐Templated Fragment Ligations—From Molecular Recognition to Drug Discovery date: 2017-05-31 pages: extension: .txt txt: ./txt/cord-328483-sj8i9ss2.txt cache: ./cache/cord-328483-sj8i9ss2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328483-sj8i9ss2.txt' === file2bib.sh === id: cord-348360-20eq5meh author: Esposito, Dominic title: Optimizing high-yield production of SARS-CoV-2 soluble spike trimers for serology assays date: 2020-06-04 pages: extension: .txt txt: ./txt/cord-348360-20eq5meh.txt cache: ./cache/cord-348360-20eq5meh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-348360-20eq5meh.txt' === file2bib.sh === id: cord-333757-h12aozg2 author: Modis, Yorgo title: Class II Fusion Proteins date: 2013-07-10 pages: extension: .txt txt: ./txt/cord-333757-h12aozg2.txt cache: ./cache/cord-333757-h12aozg2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-333757-h12aozg2.txt' === file2bib.sh === id: cord-339558-li65qvq9 author: Rana, Rashmi title: A comprehensive overview of proteomics approach for COVID 19: new perspectives in target therapy strategies date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-339558-li65qvq9.txt cache: ./cache/cord-339558-li65qvq9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339558-li65qvq9.txt' === file2bib.sh === id: cord-327883-s9nbr5y8 author: nan title: Section Virology date: 1990-03-31 pages: extension: .txt txt: ./txt/cord-327883-s9nbr5y8.txt cache: ./cache/cord-327883-s9nbr5y8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-327883-s9nbr5y8.txt' === file2bib.sh === id: cord-334220-sqvfr31q author: Messina, Francesco title: Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-334220-sqvfr31q.txt cache: ./cache/cord-334220-sqvfr31q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334220-sqvfr31q.txt' === file2bib.sh === id: cord-338468-c0jv3i1t author: Kanduc, Darja title: From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-338468-c0jv3i1t.txt cache: ./cache/cord-338468-c0jv3i1t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-338468-c0jv3i1t.txt' === file2bib.sh === id: cord-345088-krb1eidw author: Shen, S title: A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature date: 2004-09-01 pages: extension: .txt txt: ./txt/cord-345088-krb1eidw.txt cache: ./cache/cord-345088-krb1eidw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-345088-krb1eidw.txt' === file2bib.sh === id: cord-350558-qfdp4ov9 author: Shaban, Mohammed Samer title: Inhibiting coronavirus replication in cultured cells by chemical ER stress date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-350558-qfdp4ov9.txt cache: ./cache/cord-350558-qfdp4ov9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-350558-qfdp4ov9.txt' === file2bib.sh === id: cord-341324-f9g9gitn author: Rojas, José M. title: Viral pathogen-induced mechanisms to antagonize mammalian interferon (IFN) signaling pathway date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-341324-f9g9gitn.txt cache: ./cache/cord-341324-f9g9gitn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-341324-f9g9gitn.txt' === file2bib.sh === id: cord-336119-8g37xsys author: Nimgampalle, Mallikarjuna title: Screening of Chloroquine, Hydroxychloroquine and its derivatives for their binding affinity to multiple SARS-CoV-2 protein drug targets date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-336119-8g37xsys.txt cache: ./cache/cord-336119-8g37xsys.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-336119-8g37xsys.txt' === file2bib.sh === id: cord-329149-1giy1fow author: Martinez-Martin, Nadia title: Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions date: 2017-02-22 pages: extension: .txt txt: ./txt/cord-329149-1giy1fow.txt cache: ./cache/cord-329149-1giy1fow.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329149-1giy1fow.txt' === file2bib.sh === id: cord-329844-w969lczb author: Robson, B. title: Bioinformatics studies on a function of the SARS-CoV-2 spike glycoprotein as the binding of host sialic acid glycans date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-329844-w969lczb.txt cache: ./cache/cord-329844-w969lczb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329844-w969lczb.txt' === file2bib.sh === id: cord-335310-61wibso4 author: Chen, Hui-Wen title: Synthetic virus-like particles prepared via protein corona formation enable effective vaccination in an avian model of coronavirus infection date: 2016-08-15 pages: extension: .txt txt: ./txt/cord-335310-61wibso4.txt cache: ./cache/cord-335310-61wibso4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-335310-61wibso4.txt' === file2bib.sh === id: cord-342118-fsmuqktd author: Dyakov, Ilya N. title: FN3 protein fragment containing two type III fibronectin domains from B. longum GT15 binds to human tumor necrosis factor alpha in vitro date: 2020-08-06 pages: extension: .txt txt: ./txt/cord-342118-fsmuqktd.txt cache: ./cache/cord-342118-fsmuqktd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342118-fsmuqktd.txt' === file2bib.sh === id: cord-336364-2ust3qoq author: Artigas, Laura title: In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-336364-2ust3qoq.txt cache: ./cache/cord-336364-2ust3qoq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-336364-2ust3qoq.txt' === file2bib.sh === id: cord-340387-ohkjheat author: Wynne, James W. title: Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA date: 2013-01-07 pages: extension: .txt txt: ./txt/cord-340387-ohkjheat.txt cache: ./cache/cord-340387-ohkjheat.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-340387-ohkjheat.txt' === file2bib.sh === id: cord-320713-b37c8aye author: Roberts, Lisa O. title: Chapter 9 Viral Strategies to Subvert the Mammalian Translation Machinery date: 2009-10-27 pages: extension: .txt txt: ./txt/cord-320713-b37c8aye.txt cache: ./cache/cord-320713-b37c8aye.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-320713-b37c8aye.txt' === file2bib.sh === id: cord-336542-6asieplk author: Tanco, Sebastián title: Structure–Function Analysis of the Short Splicing Variant Carboxypeptidase Encoded by Drosophila melanogaster silver date: 2010-08-20 pages: extension: .txt txt: ./txt/cord-336542-6asieplk.txt cache: ./cache/cord-336542-6asieplk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336542-6asieplk.txt' === file2bib.sh === id: cord-342634-4ouhdjsr author: Semrad, Katharina title: Proteins with RNA Chaperone Activity: A World of Diverse Proteins with a Common Task—Impediment of RNA Misfolding date: 2010-12-26 pages: extension: .txt txt: ./txt/cord-342634-4ouhdjsr.txt cache: ./cache/cord-342634-4ouhdjsr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-342634-4ouhdjsr.txt' === file2bib.sh === id: cord-334592-54dofkxh author: Levine, Beth title: Autophagy in immunity and inflammation date: 2011-01-20 pages: extension: .txt txt: ./txt/cord-334592-54dofkxh.txt cache: ./cache/cord-334592-54dofkxh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-334592-54dofkxh.txt' === file2bib.sh === id: cord-323331-80d01l6f author: Li, Jie title: Golgi Structure and Function in Health, Stress, and Diseases date: 2019-01-01 pages: extension: .txt txt: ./txt/cord-323331-80d01l6f.txt cache: ./cache/cord-323331-80d01l6f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323331-80d01l6f.txt' === file2bib.sh === id: cord-341129-eo0vjcmk author: Kielian, Margaret title: Virus membrane-fusion proteins: more than one way to make a hairpin date: 2006 pages: extension: .txt txt: ./txt/cord-341129-eo0vjcmk.txt cache: ./cache/cord-341129-eo0vjcmk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-341129-eo0vjcmk.txt' === file2bib.sh === id: cord-337825-ujq9mxk7 author: Chen, Bin title: Overview of lethal human coronaviruses date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-337825-ujq9mxk7.txt cache: ./cache/cord-337825-ujq9mxk7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337825-ujq9mxk7.txt' === file2bib.sh === id: cord-333262-xvfl7ycj author: Robson, B. title: COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance date: 2020-04-11 pages: extension: .txt txt: ./txt/cord-333262-xvfl7ycj.txt cache: ./cache/cord-333262-xvfl7ycj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-333262-xvfl7ycj.txt' === file2bib.sh === id: cord-354050-kcn67stj author: Shi, Guoli title: More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins date: 2017-11-21 pages: extension: .txt txt: ./txt/cord-354050-kcn67stj.txt cache: ./cache/cord-354050-kcn67stj.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-354050-kcn67stj.txt' === file2bib.sh === id: cord-341564-fvuwick5 author: Qi, Zhao-Hui title: Novel Method of 3-Dimensional Graphical Representation for Proteins and Its Application date: 2018-06-12 pages: extension: .txt txt: ./txt/cord-341564-fvuwick5.txt cache: ./cache/cord-341564-fvuwick5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341564-fvuwick5.txt' === file2bib.sh === id: cord-352371-t54zftal author: Kumar, Ravindra title: Prediction of endoplasmic reticulum resident proteins using fragmented amino acid composition and support vector machine date: 2017-09-04 pages: extension: .txt txt: ./txt/cord-352371-t54zftal.txt cache: ./cache/cord-352371-t54zftal.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352371-t54zftal.txt' === file2bib.sh === id: cord-349774-898tmq14 author: Zhang, Haiyang title: Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-349774-898tmq14.txt cache: ./cache/cord-349774-898tmq14.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349774-898tmq14.txt' === file2bib.sh === id: cord-337067-j8ebslif author: Mades, Andreas title: Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins date: 2012-11-15 pages: extension: .txt txt: ./txt/cord-337067-j8ebslif.txt cache: ./cache/cord-337067-j8ebslif.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-337067-j8ebslif.txt' === file2bib.sh === id: cord-347714-vxxhglx7 author: Abitogun, Folagbade title: COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-347714-vxxhglx7.txt cache: ./cache/cord-347714-vxxhglx7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347714-vxxhglx7.txt' === file2bib.sh === id: cord-296347-fanlvxqs author: Loureiro, Joana title: Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions date: 2006-12-02 pages: extension: .txt txt: ./txt/cord-296347-fanlvxqs.txt cache: ./cache/cord-296347-fanlvxqs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-296347-fanlvxqs.txt' === file2bib.sh === id: cord-329448-kxxy60x9 author: Kumari, Sudha title: Endocytosis unplugged: multiple ways to enter the cell date: 2010-02-02 pages: extension: .txt txt: ./txt/cord-329448-kxxy60x9.txt cache: ./cache/cord-329448-kxxy60x9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-329448-kxxy60x9.txt' === file2bib.sh === id: cord-356019-k7gs1ohp author: Makhzoum, Abdullah title: Recent advances on host plants and expression cassettes' structure and function in plant molecular pharming date: 2013-08-20 pages: extension: .txt txt: ./txt/cord-356019-k7gs1ohp.txt cache: ./cache/cord-356019-k7gs1ohp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-356019-k7gs1ohp.txt' === file2bib.sh === id: cord-350935-p6euuop3 author: Doğan, Tunca title: CROssBAR: Comprehensive Resource of Biomedical Relations with Deep Learning Applications and Knowledge Graph Representations date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-350935-p6euuop3.txt cache: ./cache/cord-350935-p6euuop3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350935-p6euuop3.txt' === file2bib.sh === id: cord-355477-7xd93aqv author: SATIJA, NAMITA title: The Molecular Biology of SARS Coronavirus date: 2007-04-23 pages: extension: .txt txt: ./txt/cord-355477-7xd93aqv.txt cache: ./cache/cord-355477-7xd93aqv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-355477-7xd93aqv.txt' === file2bib.sh === id: cord-350423-yaeduwvb author: James, Claire D. title: Viral Interactions with PDZ Domain-Containing Proteins—An Oncogenic Trait? date: 2016-01-18 pages: extension: .txt txt: ./txt/cord-350423-yaeduwvb.txt cache: ./cache/cord-350423-yaeduwvb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350423-yaeduwvb.txt' === file2bib.sh === id: cord-342189-ya05m58o author: Banerjee, Abhik K. title: SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-342189-ya05m58o.txt cache: ./cache/cord-342189-ya05m58o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-342189-ya05m58o.txt' === file2bib.sh === id: cord-343791-0vykwml5 author: Hainline, Kelly M. title: Progress towards the clinical translation of bio-inspired peptide and protein assemblies date: 2017-11-08 pages: extension: .txt txt: ./txt/cord-343791-0vykwml5.txt cache: ./cache/cord-343791-0vykwml5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-343791-0vykwml5.txt' === file2bib.sh === id: cord-352172-g0jiaenw author: Stoevesandt, Oda title: Protein microarrays: high-throughput tools for proteomics date: 2014-01-09 pages: extension: .txt txt: ./txt/cord-352172-g0jiaenw.txt cache: ./cache/cord-352172-g0jiaenw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-352172-g0jiaenw.txt' === file2bib.sh === id: cord-351559-az4pgi9k author: Turjya, Rafeed Rahman title: Perversely expressed long noncoding RNAs can alter host response and viral proliferation in SARS-CoV-2 infection date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-351559-az4pgi9k.txt cache: ./cache/cord-351559-az4pgi9k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-351559-az4pgi9k.txt' === file2bib.sh === id: cord-337158-0iw2kcaf author: Tiernan, Hannah title: ATR-FTIR spectroscopy and spectroscopic imaging for the analysis of biopharmaceuticals date: 2020-06-22 pages: extension: .txt txt: ./txt/cord-337158-0iw2kcaf.txt cache: ./cache/cord-337158-0iw2kcaf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337158-0iw2kcaf.txt' === file2bib.sh === id: cord-345712-gmzue6lj author: Palazzo, Luca title: ADP‐ribosylation: new facets of an ancient modification date: 2017-04-26 pages: extension: .txt txt: ./txt/cord-345712-gmzue6lj.txt cache: ./cache/cord-345712-gmzue6lj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345712-gmzue6lj.txt' === file2bib.sh === id: cord-355924-8sk9al0n author: Allam, Loubna title: Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-355924-8sk9al0n.txt cache: ./cache/cord-355924-8sk9al0n.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-355924-8sk9al0n.txt' === file2bib.sh === id: cord-355327-d3gcfepx author: Fan, Samuel W title: Conformational changes in redox pairs of protein structures date: 2009-08-01 pages: extension: .txt txt: ./txt/cord-355327-d3gcfepx.txt cache: ./cache/cord-355327-d3gcfepx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-355327-d3gcfepx.txt' === file2bib.sh === id: cord-356064-q56jnhss author: Bartel, Sebastian title: Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides date: 2011-08-01 pages: extension: .txt txt: ./txt/cord-356064-q56jnhss.txt cache: ./cache/cord-356064-q56jnhss.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-356064-q56jnhss.txt' === file2bib.sh === id: cord-347661-q9lgliph author: Zevenhoven-Dobbe, Jessika C. title: Production of Monospecific Rabbit Antisera Recognizing Nidovirus Proteins date: 2007-11-28 pages: extension: .txt txt: ./txt/cord-347661-q9lgliph.txt cache: ./cache/cord-347661-q9lgliph.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347661-q9lgliph.txt' === file2bib.sh === id: cord-355913-fhvt1ht1 author: Burrell, Christopher J. title: Virus Replication date: 2016-11-11 pages: extension: .txt txt: ./txt/cord-355913-fhvt1ht1.txt cache: ./cache/cord-355913-fhvt1ht1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-355913-fhvt1ht1.txt' === file2bib.sh === id: cord-330852-n7j0c4ne author: Fischer, Wolfgang B. title: Mechanism of Function of Viral Channel Proteins and Implications for Drug Development date: 2012-02-23 pages: extension: .txt txt: ./txt/cord-330852-n7j0c4ne.txt cache: ./cache/cord-330852-n7j0c4ne.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-330852-n7j0c4ne.txt' === file2bib.sh === id: cord-339091-3xk2w0d2 author: Flower, Darren R title: Computer aided selection of candidate vaccine antigens date: 2010-11-03 pages: extension: .txt txt: ./txt/cord-339091-3xk2w0d2.txt cache: ./cache/cord-339091-3xk2w0d2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-339091-3xk2w0d2.txt' === file2bib.sh === id: cord-354547-eomm1sl5 author: Wang, Jibin title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding date: 2009-03-16 pages: extension: .txt txt: ./txt/cord-354547-eomm1sl5.txt cache: ./cache/cord-354547-eomm1sl5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354547-eomm1sl5.txt' === file2bib.sh === id: cord-350286-n7ylgqfu author: Giri, Rajanish title: When Darkness Becomes a Ray of Light in the Dark Times: Understanding the COVID-19 via the Comparative Analysis of the Dark Proteomes of SARS-CoV-2, Human SARS and Bat SARS-Like Coronaviruses date: 2020-04-03 pages: extension: .txt txt: ./txt/cord-350286-n7ylgqfu.txt cache: ./cache/cord-350286-n7ylgqfu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350286-n7ylgqfu.txt' === file2bib.sh === id: cord-346314-o9fjpqaj author: Jarboui, Mohamed Ali title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus date: 2012-11-15 pages: extension: .txt txt: ./txt/cord-346314-o9fjpqaj.txt cache: ./cache/cord-346314-o9fjpqaj.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346314-o9fjpqaj.txt' === file2bib.sh === id: cord-354030-8tfg881h author: Dong, Rong title: Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-354030-8tfg881h.txt cache: ./cache/cord-354030-8tfg881h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354030-8tfg881h.txt' === file2bib.sh === id: cord-352481-iq3wor3w author: Postic, Guillaume title: An information gain-based approach for evaluating protein structure models date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-352481-iq3wor3w.txt cache: ./cache/cord-352481-iq3wor3w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352481-iq3wor3w.txt' === file2bib.sh === id: cord-341701-zropd3mo author: Adhikari, Subash title: A high-stringency blueprint of the human proteome date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-341701-zropd3mo.txt cache: ./cache/cord-341701-zropd3mo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-341701-zropd3mo.txt' === file2bib.sh === id: cord-354950-kmpbdvof author: Demurtas, Olivia C. title: Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS date: 2016-02-05 pages: extension: .txt txt: ./txt/cord-354950-kmpbdvof.txt cache: ./cache/cord-354950-kmpbdvof.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354950-kmpbdvof.txt' === file2bib.sh === id: cord-355377-b0rcg3rt author: van der Vlag, R. title: Analytical Methods in Protein-Templated Dynamic Combinatorial Chemistry date: 2017-06-29 pages: extension: .txt txt: ./txt/cord-355377-b0rcg3rt.txt cache: ./cache/cord-355377-b0rcg3rt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-355377-b0rcg3rt.txt' === file2bib.sh === id: cord-348972-r94fhpe0 author: Gussow, Ayal B. title: Machine-learning approach expands the repertoire of anti-CRISPR protein families date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-348972-r94fhpe0.txt cache: ./cache/cord-348972-r94fhpe0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-348972-r94fhpe0.txt' === file2bib.sh === id: cord-346965-0oq2n0af author: Liu, Zhi-Ping title: Bridging protein local structures and protein functions date: 2008-04-18 pages: extension: .txt txt: ./txt/cord-346965-0oq2n0af.txt cache: ./cache/cord-346965-0oq2n0af.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-346965-0oq2n0af.txt' === file2bib.sh === id: cord-346916-jj4l9ydl author: Girardi, Erika title: Roadblocks and fast tracks: How RNA binding proteins affect the viral RNA journey in the cell date: 2020-08-23 pages: extension: .txt txt: ./txt/cord-346916-jj4l9ydl.txt cache: ./cache/cord-346916-jj4l9ydl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-346916-jj4l9ydl.txt' === file2bib.sh === id: cord-342756-rgm9ffpk author: Senger, Mario Roberto title: COVID-19: molecular targets, drug repurposing and new avenues for drug discovery date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-342756-rgm9ffpk.txt cache: ./cache/cord-342756-rgm9ffpk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-342756-rgm9ffpk.txt' === file2bib.sh === id: cord-334511-lx9608vy author: Emwas, Abdul-Hamid title: NMR as a “Gold Standard” Method in Drug Design and Discovery date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-334511-lx9608vy.txt cache: ./cache/cord-334511-lx9608vy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-334511-lx9608vy.txt' === file2bib.sh === id: cord-023208-w99gc5nx author: nan title: Poster Presentation Abstracts date: 2006-09-01 pages: extension: .txt txt: ./txt/cord-023208-w99gc5nx.txt cache: ./cache/cord-023208-w99gc5nx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-023208-w99gc5nx.txt' === file2bib.sh === id: cord-023225-5quigar4 author: nan title: Posters date: 2012-08-21 pages: extension: .txt txt: ./txt/cord-023225-5quigar4.txt cache: ./cache/cord-023225-5quigar4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-023225-5quigar4.txt' === file2bib.sh === id: cord-004879-pgyzluwp author: nan title: Programmed cell death date: 1994 pages: extension: .txt txt: ./txt/cord-004879-pgyzluwp.txt cache: ./cache/cord-004879-pgyzluwp.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 5 resourceName b'cord-004879-pgyzluwp.txt' === file2bib.sh === id: cord-347710-ff64y6ef author: Wan, Qianya title: Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-347710-ff64y6ef.txt cache: ./cache/cord-347710-ff64y6ef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-347710-ff64y6ef.txt' === file2bib.sh === id: cord-006860-a3b8hyyr author: nan title: 40th Annual Meeting of the GTH (Gesellschaft für Thrombose- und Hämostaseforschung) date: 1996 pages: extension: .txt txt: ./txt/cord-006860-a3b8hyyr.txt cache: ./cache/cord-006860-a3b8hyyr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-006860-a3b8hyyr.txt' === file2bib.sh === id: cord-004584-bcw90f5b author: nan title: Abstracts: 8th EBSA European Biophysics Congress, August 23rd–27th 2011, Budapest, Hungary date: 2011-08-06 pages: extension: .txt txt: ./txt/cord-004584-bcw90f5b.txt cache: ./cache/cord-004584-bcw90f5b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 27 resourceName b'cord-004584-bcw90f5b.txt' === file2bib.sh === id: cord-023209-un2ysc2v author: nan title: Poster Presentations date: 2008-10-07 pages: extension: .txt txt: ./txt/cord-023209-un2ysc2v.txt cache: ./cache/cord-023209-un2ysc2v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-023209-un2ysc2v.txt' === file2bib.sh === id: cord-006229-7yoilsho author: nan title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date: 2016-02-06 pages: extension: .txt txt: ./txt/cord-006229-7yoilsho.txt cache: ./cache/cord-006229-7yoilsho.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 23 resourceName b'cord-006229-7yoilsho.txt' === file2bib.sh === id: cord-001835-0s7ok4uw author: nan title: Abstracts of the 29th Annual Symposium of The Protein Society date: 2015-10-01 pages: extension: .txt txt: ./txt/cord-001835-0s7ok4uw.txt cache: ./cache/cord-001835-0s7ok4uw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 11 resourceName b'cord-001835-0s7ok4uw.txt' === file2bib.sh === id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 pages: extension: .txt txt: ./txt/cord-006230-xta38e7j.txt cache: ./cache/cord-006230-xta38e7j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-006230-xta38e7j.txt' === file2bib.sh === id: cord-004534-jqm1hxps author: nan title: Abstract date: 2009-06-09 pages: extension: .txt txt: ./txt/cord-004534-jqm1hxps.txt cache: ./cache/cord-004534-jqm1hxps.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 14 resourceName b'cord-004534-jqm1hxps.txt' === file2bib.sh === id: cord-008777-i2reanan author: nan title: ECB12: 12th European Congess on Biotechnology date: 2005-07-19 pages: extension: .txt txt: ./txt/cord-008777-i2reanan.txt cache: ./cache/cord-008777-i2reanan.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 15 resourceName b'cord-008777-i2reanan.txt' === file2bib.sh === id: cord-023026-2r84ndzv author: nan title: Posters date: 2013-06-14 pages: extension: .txt txt: ./txt/cord-023026-2r84ndzv.txt cache: ./cache/cord-023026-2r84ndzv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 11 resourceName b'cord-023026-2r84ndzv.txt' === file2bib.sh === id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 pages: extension: .txt txt: ./txt/cord-022888-dnsdg04n.txt cache: ./cache/cord-022888-dnsdg04n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 14 resourceName b'cord-022888-dnsdg04n.txt' === file2bib.sh === id: cord-031907-ilhr3iu5 author: nan title: ISEV2020 Abstract Book date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-031907-ilhr3iu5.txt cache: ./cache/cord-031907-ilhr3iu5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 33 resourceName b'cord-031907-ilhr3iu5.txt' === file2bib.sh === id: cord-022940-atbjwpo5 author: nan title: Poster Sessions date: 2016-09-07 pages: extension: .txt txt: ./txt/cord-022940-atbjwpo5.txt cache: ./cache/cord-022940-atbjwpo5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 18 resourceName b'cord-022940-atbjwpo5.txt' Que is empty; done keyword-protein-cord === reduce.pl bib === id = cord-002739-7t1o19kn author = Yu, Xiaobo title = Multiplexed Nucleic Acid Programmable Protein Arrays date = 2017-09-20 pages = extension = .txt mime = text/plain words = 6451 sentences = 296 flesch = 49 summary = Methods: In this work, we developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA), which significantly increases the number of displayed proteins by multiplexing as many as five different gene plasmids within a printed spot. Protein-protein interactions and serological antibody assays using human viral proteome microarrays demonstrated that comparable hits were detected by M-NAPPA and non-multiplexed NAPPA arrays. We developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA) method by combining as many as five different DNA plasmids within one spot, which increases the number of displayed proteins per microarray by five-fold. To decrease the cost of high throughput screening experiments, we hypothesized that the plasmid cDNA encoding for different proteins could be multiplexed (by combining M different plasmids) within each feature to create a high-density array, M-NAPPA ( Figure 1A) . Since the multiplex concept to increase feature density was successful in detecting protein-protein interactions and serological antibody responses on planar microarrays, we wanted to determine whether M-NAPPA could also be applied to a nano-well microarray platform. cache = ./cache/cord-002739-7t1o19kn.txt txt = ./txt/cord-002739-7t1o19kn.txt === reduce.pl bib === id = cord-001435-ebl8yc92 author = Hoppe, Sebastian title = Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae date = 2014-10-21 pages = extension = .txt mime = text/plain words = 9619 sentences = 545 flesch = 50 summary = Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen. Incubation with antibodies reactive to either of those two bacterial species resulted in signal intensities in the neighbourhood of the negative control independent of sequence alterations, see Figure 11 . In contrast, the other two proteins displaying linear epitopes, KPN_00363 and KPN_00459, indicated some specificity with the antibodies tested and two linear consensus sequences could be derived, GAVVALSTTFA and GIAFGAVELFD, respectively. cache = ./cache/cord-001435-ebl8yc92.txt txt = ./txt/cord-001435-ebl8yc92.txt === reduce.pl bib === id = cord-003144-nqkw5v3w author = Qu, Zehui title = Label‐Free Quantitative Proteomic Analysis of Differentially Expressed Membrane Proteins of Pulmonary Alveolar Macrophages Infected with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Its Attenuated Strain date = 2017-11-24 pages = extension = .txt mime = text/plain words = 5514 sentences = 319 flesch = 51 summary = title: Label‐Free Quantitative Proteomic Analysis of Differentially Expressed Membrane Proteins of Pulmonary Alveolar Macrophages Infected with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Its Attenuated Strain Significant differences exist between the highly pathogenic (HP) porcine reproductive and respiratory syndrome virus (PRRSV) and its attenuated pathogenic (AP) strain in the ability to infect host cells. This is the first attempt to explore the differential characteristics between HP‐PRRSV and its attenuated PRRSV infected PAMs focusing on membrane proteins which will be of great help to further understand the different infective mechanisms of HP‐PRRSV and AP‐PRRSV. Differentially expressed proteins between control and HP-PRRSV-infected cells (Con/HP) and the www.advancedsciencenews.com www.proteomics-journal.com p <0.01 and ratio >2 or <0.5 indicated quantitative difference between two groups. By analyzing detected proteins in HP-infected, AP-PRRSV-infected, and control group, proteins related to the immune response or virus replication were identified that may elucidate unique pathways used by different virulent PRRSVs for cell entry, virus replication, and immune escape mechanisms. cache = ./cache/cord-003144-nqkw5v3w.txt txt = ./txt/cord-003144-nqkw5v3w.txt === reduce.pl bib === id = cord-004719-3stcx0dd author = Mushegian, A. R. title = Cell-to-cell movement of plant viruses: Insights from amino acid sequence comparisons of movement proteins and from analogies with cellular transport systems date = 1993 pages = extension = .txt mime = text/plain words = 6347 sentences = 280 flesch = 44 summary = In several groups of positive-strand RNA viruses, the movement function is provided by the proteins encoded by the so-called triple gene block including two putative small membrane-associated proteins and a putative RNA helicase. It is concluded that classification of movement proteins based on comparison of their amino acid sequences does not correlate with the type of genome nucleic acid or with grouping of viruses based on phylogenetic analysis of replicative proteins or with the virus host range. Limited sequence similarities were observed between i) movement proteins of dianthoviruses and the MIP family of cellular integral membrane proteins, and ii) between movement proteins of bromoviruses and cucumoviruses and M1 protein of influenza viruses which is involved in nuclear export of viral ribonucleoproteins. With representative sequences of plant virus genomes from many groups available, efforts were made to identify regions of similarity between known movement proteins and to predict movement functions for uncharacterized ORFs. Early observations made by this approach have been reviewed previously (e.g. cache = ./cache/cord-004719-3stcx0dd.txt txt = ./txt/cord-004719-3stcx0dd.txt === reduce.pl bib === id = cord-003761-ikni2acz author = Li, Zengbin title = Biological Function and Application of Picornaviral 2B Protein: A New Target for Antiviral Drug Development date = 2019-06-04 pages = extension = .txt mime = text/plain words = 6425 sentences = 331 flesch = 39 summary = In this review, we mainly summarize recent research data on the viroporin or viroporin-like activity of 2B proteins, which affects the biological function of the membrane, regulates cell death, and affects the host immune response. In particular, the 2B protein may change the Ca 2+ concentration to regulate autophagy and apoptosiswhich are distinct cell death mechanisms controlled by the virus to effectively evade the host immunity, thereby promoting viral replication and release [48] [49] [50] [51] [52] . Thus, the main points of focus for research on the structure and function of the 2B protein toward ultimate drug development are: (1) mechanism of increasing membrane permeability to disturb the ion balance, (2) regulation of autophagy and apoptosis, (3) inhibition of the host immune response, and (4) promotion of viral replication and release. cache = ./cache/cord-003761-ikni2acz.txt txt = ./txt/cord-003761-ikni2acz.txt === reduce.pl bib === id = cord-000182-ni6iyzdn author = He, Zhisong title = Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features date = 2010-03-11 pages = extension = .txt mime = text/plain words = 6037 sentences = 305 flesch = 46 summary = title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features Many researchers have made lots of efforts to develop useful algorithms and softwares to investigate various drug-related biological problems, such as HIV protease cleavage site prediction [18, 19] , identification of GPCR (G protein-coupled receptors) type [20, 21] , protein signal peptide prediction [22] , protein subcellular location prediction [23, 24, 25] , analysis of specificity of GalNAc-transferase protein [26] , identification of protease type [27, 28] , membrane protein type prediction [29, 30, 31, 32] , and a series of relevant webserver predictors as summarized in a recent review [33] . The drug-target benchmark datasets thus obtained for enzymes, ion-channels, GPCRs, and nuclear receptors are given in Online Supporting Information S1, S2, S3, and S4, respectively. Prediction of G-protein-coupled receptor classes based on the concept of Chou's pseudo amino acid composition: an approach from discrete wavelet transform cache = ./cache/cord-000182-ni6iyzdn.txt txt = ./txt/cord-000182-ni6iyzdn.txt === reduce.pl bib === id = cord-001244-qdld7hdc author = Fan, Yue-Nong title = iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking date = 2014-03-19 pages = extension = .txt mime = text/plain words = 6502 sentences = 339 flesch = 46 summary = In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. [59] did not provide a publicly accessible web-server for their method, and hence its practical application value is quite limited, particularly for the broad experimental scientists; (b) The prediction quality can be further enhanced by incorporating some key features into the formulation of NR-drug (nuclear receptor and drug) samples via the general form of pseudo amino acid composition [60] . Prediction of G-protein-coupled receptor classes based on the concept of Chou's pseudo amino acid composition: An approach from discrete wavelet transform cache = ./cache/cord-001244-qdld7hdc.txt txt = ./txt/cord-001244-qdld7hdc.txt === reduce.pl bib === id = cord-001726-d7iwkatn author = Henry, Kevin A. title = Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold date = 2015-08-04 pages = extension = .txt mime = text/plain words = 10444 sentences = 516 flesch = 39 summary = Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage's potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage's large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. While in some cases the results of these studies have been promising, antibody epitope-based peptide vaccines are no longer an area of active research for several reasons: (i) in many cases, peptides incompletely or inadequately mimic epitopes on folded proteins (Irving et al., 2010 ; see below); (ii) antibodies against a single epitope may be of limited utility, especially for highly variable pathogens (Van Regenmortel, 2012); and (iii) for pathogens for which protective immune responses are generated efficiently during natural infection, peptide vaccines offer few advantages over recombinant subunit and live vector vaccines, which have become easier to produce over time. cache = ./cache/cord-001726-d7iwkatn.txt txt = ./txt/cord-001726-d7iwkatn.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-002100-dt5zvebj author = He, Yonghua title = Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF) date = 2016-06-17 pages = extension = .txt mime = text/plain words = 6795 sentences = 336 flesch = 45 summary = Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. Epidermal growth factor protein from humans was produced in soybean seeds by constructing a plant gene expression cassette that involved a synthetic codon optimized EGF nucleotide sequence (protein sequence from Genbank accession CCQ43157). To assess the bioactivity of soybean-produced hEGF, samples were prepared from both ShEGF transgenic soybean lines and nontransgenic controls that were used to stimulate HeLa cells to induce EGFR internalization, degradation and phosphorylation. In contrast, samples prepared from control nontransgenic soybeans exhibited no apparent bioactivity showing the degradation and phosphorylation of EGFR is the result of EGF binding of either commercial rhEGF added to the media or from the hEGF produced by the transgenic soybeans. cache = ./cache/cord-002100-dt5zvebj.txt txt = ./txt/cord-002100-dt5zvebj.txt === reduce.pl bib === id = cord-001898-ntqyjqqk author = Huang, Chih-Wei title = Lys-315 at the Interfaces of Diagonal Subunits of δ-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly date = 2016-01-05 pages = extension = .txt mime = text/plain words = 6578 sentences = 337 flesch = 47 summary = The changes in tryptophan fluorescence were Dilution of monomeric K315A mutant protein denatured in 5 M GdmCl resulted in refolding to a similar conformation as the original monomeric state (Fig 5A and 5B) . Since refolding of partly unfolded monomeric mutant δ-crystallin resulted in a conformation with high exposure of hydrophobic regions, the occurrence of protein aggregation in the process was determined using light scattering measurement. An increase in fluorescence intensity resulting from binding of ThT with the aggregates over time was observed following dilution of 0.84 and 3 M GdmCl denatured monomeric mutant δ-crystallin into buffer (Fig 6B) . The unique stable conformation from unfolding of K315A mutant protein in the presence of urea suggests that the interactions provided by this residue at the interfaces may play a critical role in stabilization of the quaternary structure of δ-crystallin. cache = ./cache/cord-001898-ntqyjqqk.txt txt = ./txt/cord-001898-ntqyjqqk.txt === reduce.pl bib === id = cord-009959-erh8ggh3 author = BENTLEY, WILLIAM E. title = Development of an Efficient Bioprocess for Poultry Vaccines Using High‐density Insect Cell Culture date = 2006-12-17 pages = extension = .txt mime = text/plain words = 5803 sentences = 325 flesch = 50 summary = Several general articles, manuals, and review articles have been published that describe both the expression system'" and novel process engineering aspects.%" In this work, we subdivide the entire bioprocess into three key areas: (1) metabolism of infected cells and specific heterologous protein yield; (2) bioreactor configuration and high cell density continuous culture; and (3) integration of expression and product separation. Caron el al." restored recombinant protein production at higher cell density by renewing the medium at the time of infection. High-level recombinant protein production in bioreactors using the baculovirus insect cell expression system Quantification of cell culture factors affecting recombinant protein yields in baculovirus-infected insect cells Effects of oxygen/glucose/glutamine feeding on insect cell baculovirus protein expression: A study on epoxide hydroxylase production Ecdysteroids increase the yield of recombinant protein produced in baculovirus insect cell expression system A continuous flow bioreactor system for the production of recombinant proteins using the insect cell-baculovirus expression system cache = ./cache/cord-009959-erh8ggh3.txt txt = ./txt/cord-009959-erh8ggh3.txt === reduce.pl bib === id = cord-013046-r6dtiu97 author = Liu, Bin title = Combining evolutionary information extracted from frequency profiles with sequence-based kernels for protein remote homology detection date = 2014-02-15 pages = extension = .txt mime = text/plain words = 6945 sentences = 347 flesch = 52 summary = title: Combining evolutionary information extracted from frequency profiles with sequence-based kernels for protein remote homology detection For instance, the kernel combination methodology (VBKC) (Damoulas and Girolami, 2008 ) used a single multiclass kernel machine to combine various kernels based on different feature spaces; SVM-physicochemical distance transformation (PDT) (Liu et al., 2012) combined the amino acid physicochemical properties and the profile features via PDT to incorporate the local sequence-order information of the entire protein sequences. The results obtained by these four methods on the SCOP benchmark are listed in Supplementary Table S1 of Supplementary Material S4, from which we can see that the current method outperforms SVM-Top-n-gram-combine-LSA (Liu et al., 2008) , SVM-PDT-Profile (Liu et al., 2012) and BioSVM-2L (Muda et al., 2011) and is highly comparable with Profile (Kuang et al., 2005) and HHSearch (So¨ding, 2005) , indicating that the profile-based protein representation is a promising approach to extract the evolutionary information from frequency profiles for protein remote homology detection. Protein remote homology detection by combining Chou's pseudo amino acid composition and profile-based protein representation cache = ./cache/cord-013046-r6dtiu97.txt txt = ./txt/cord-013046-r6dtiu97.txt === reduce.pl bib === id = cord-004673-c8qcjve9 author = Faaberg, K. S. title = Membrane association of the C-terminal half of the open reading frame 1a protein of lactate dehydrogenase-elevating virus date = 1996 pages = extension = .txt mime = text/plain words = 4647 sentences = 220 flesch = 55 summary = cDNAs encoding ORF 1a protein segments encompassing transmembrane segments 5 to 11 and its amphipathic C-terminal end as well as the N-terminal 80 amino acids of the downstream ORF 1b protein were transcribed and the transcripts in vitro translated in the absence and presence of microsomal membranes. Eisenberg hydrophobic moment analysis of the protein predicted the presence of eleven transmembrane segments in the C-terminal half of the molecule (amino acids 980-1852) that flank the serine protease domain, cDNAs encoding ORF la protein segments encompassing transmembrane segments 5 to 11 and its amphipathic C-terminal end as well as the N-terminal 80 amino acids of the downstream ORF lb protein were transcribed and the transcripts in vitro translated in the absence and presence of microsomal membranes. In the present study we provide strong evidence that the segment of LDV ORF la protein with transmembrane segments 5-11 (see Fig. 1 ) becomes intimately associated with endoplasmic reticulum (ER) membranes during synthesis and that none of its potential N-glycosylation sites becomes glycosylated. cache = ./cache/cord-004673-c8qcjve9.txt txt = ./txt/cord-004673-c8qcjve9.txt === reduce.pl bib === id = cord-003297-fewy8y4a author = Wang, Ming-Yang title = A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs date = 2018-09-18 pages = extension = .txt mime = text/plain words = 9154 sentences = 486 flesch = 48 summary = A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds. To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions. The contour maps around aconitine alkaloids generated by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) were combined with the interactions between ligand substituents and amino acids obtained from docking results to gain insight on the relationship between the structure of aconitine alkaloids and their toxicity. Finally, we combined the ligand-based 3D-QSTR analysis with the structure-based molecular docking study to identify the necessary moiety related to the cardiotoxicity mechanism of the aconitine alkaloids (in Figure 10 ). cache = ./cache/cord-003297-fewy8y4a.txt txt = ./txt/cord-003297-fewy8y4a.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-003817-k3m72uxw author = Braun, Elisabeth title = Furin‐mediated protein processing in infectious diseases and cancer date = 2019-08-05 pages = extension = .txt mime = text/plain words = 9070 sentences = 557 flesch = 41 summary = For example, avirulent Newcastle disease virus (NDV) strains harbour a monobasic cleavage site in their Fusion (F) protein and result only in local infections (mainly in the respiratory tract) since expression of the respective host proteases is limited to a few cell types. Notably, proteolytic processing of Env depends on correct N-linked glycosylation as aberrant carbohydrate side chains may result in subcellular mistrafficking or sequestration of Env. 49 Most likely, HIV-1 takes advantage of the redundancy of several proprotein convertases recognising the polybasic cleavage motif in Env. Furin, PCSK5, PCSK6 and PCSK7 have all been shown to cleave gp160 in cells, albeit with different efficiencies. 59, 60 Notably, a subset of H9N2 lowly pathogenic avian influenza A virus strains also harbour R-S-K-R↓ or R-S-R-R↓ sites that are not only cleaved by trypsin-like proteases, such as TMPRSS2 or HAT, but also by PCSKs. 61 However, their cleavage is only efficient in the presence of very high amounts of furin or upon mutation of a glycosylation site in HA. cache = ./cache/cord-003817-k3m72uxw.txt txt = ./txt/cord-003817-k3m72uxw.txt === reduce.pl bib === id = cord-012682-7goljir4 author = Yuan, Meng title = N-myristoylation: from cell biology to translational medicine date = 2020-03-18 pages = extension = .txt mime = text/plain words = 7187 sentences = 347 flesch = 38 summary = N-myristoylation refers to the attachment of 14-carbon fatty acid myristates to the N-terminal glycine of proteins by N-myristoyltransferases (NMT) and affects their physiology such as plasma targeting, subcellular tracking and localization, thereby influencing the function of proteins. For example, it was reported that both N-myristoylation and palmitoylation appear to have opposing roles and different membrane lipid microdomain preferences for the G protein-membrane interactions I (Gαi1) monomer, which are likely due to the conformational differences in the presence of different fatty acids [31] . Potential targets of cancer treatments Given that altered NMT expression is observed in many types of cancer tissues and because many N-myristoylated proteins are involved in signaling processes that regulate cell proliferation, growth and death, it has been proposed that N-myristoylation or NMTs can be considered as therapeutic targets for cancer. cache = ./cache/cord-012682-7goljir4.txt txt = ./txt/cord-012682-7goljir4.txt === reduce.pl bib === id = cord-000708-iuo2cw23 author = Lippé, Roger title = Deciphering Novel Host–Herpesvirus Interactions by Virion Proteomics date = 2012-05-28 pages = extension = .txt mime = text/plain words = 5052 sentences = 261 flesch = 43 summary = These studies include the alphaherpesvirinae herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV; Loret et al., 2008; Kramer et al., 2011) , the betaherpesvirinae human and murine cytomegaloviruses (HCMV and MCMV, respectively; Kattenhorn et al., 2004; Varnum et al., 2004) and the gammaherpesvirinae Kaposi sarcoma herpesvirus (KSHV), gamma herpesvirus 68 (γHV68), Epstein-Barr virus (EBV), and Alcelaphine (Bortz et al., 2003; Johannsen et al., 2004; Bechtel et al., 2005; Zhu et al., 2005; Dry et al., 2008) . Cellular stress rather than stage of the cell cycle enhances the replication and plating efficiencies of herpes simplex virus type 1 ICP0-viruses Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0 Herpes simplex virus 1 alpha regulatory protein ICP0 interacts with and stabilizes the cell cycle regulator cyclin D3 Identification and functional evaluation of cellular and viral factors involved in the alteration of nuclear architecture during herpes simplex virus 1 infection cache = ./cache/cord-000708-iuo2cw23.txt txt = ./txt/cord-000708-iuo2cw23.txt === reduce.pl bib === === reduce.pl bib === id = cord-014368-4nasrbs6 author = nan title = Gene Chip for Viral Discovery date = 2003-11-17 pages = extension = .txt mime = text/plain words = 10009 sentences = 438 flesch = 49 summary = As they report in this paper, Miguel Nicolelis and colleagues have helped clarify some of the fundamental issues surrounding the programming and use of BMIs. Presenting results from a series of long-term studies in monkeys, they demonstrate that the same set of brain cells can control two distinct movements, the reaching and grasping of a robotic arm. RAG genes regulate the genetic recombination and ultimate cell surface expression of TCRs. Using chemical inhibitors and mutant human T cell lines deficient in critical signaling components involved in antigen receptor-dependent pathways, the researchers found that the loss of specific functions or specific proteins affected an unexpected set of target genes. But these studies also establish a model for investigating other signaling systems, to determine whether biologically functional basal signaling is a rare phenomenon or whether it is a fundamental cell process needed to control the profile of gene expression in the quiescent state. cache = ./cache/cord-014368-4nasrbs6.txt txt = ./txt/cord-014368-4nasrbs6.txt === reduce.pl bib === id = cord-000642-mkwpuav6 author = Moreira, Rebeca title = Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing date = 2012-04-19 pages = extension = .txt mime = text/plain words = 6848 sentences = 372 flesch = 45 summary = title: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum. Moreover, a few transcripts encoded by genes putatively involved in the clam immune response against Perkinsus olseni have been reported by cDNA library sequencing [18] . philippinarum transcriptome and another four bivalve species sequences were analyzed by comparative genomics (Crassostrea gigas of the family Ostreidae, Bathymodiolus azoricus and Mytilus galloprovincialis of the family Mytilidae and Laternula elliptica of the family Laternulidae). cache = ./cache/cord-000642-mkwpuav6.txt txt = ./txt/cord-000642-mkwpuav6.txt === reduce.pl bib === id = cord-002973-bkr4ndl2 author = Seifi, Morteza title = Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms date = 2018-04-17 pages = extension = .txt mime = text/plain words = 5062 sentences = 237 flesch = 40 summary = Our results showed that for PITX2, and likely other members of this homeodomain transcription factor family, MutPred, Provean, PMUT, molecular modeling, and CUPSAT can reliably be used to predict PITX2 missense variants pathogenicity. The protein sequence and/or protein structure with mutational position and amino acid residue of 18 previously functionally characterized pathogenic PITX2 missense variants, plus 16 SNPs with a population frequency of higher than 0.05% (thus considered benign polymorphisms), were used to test the predictive value of eleven common bioinformatics prediction programs; SIFT, PolyPhen-2, PANTHER-PSEP, MutPred, MutationTaster, Provean, PMUT, FATHMM, nsSNPAnalyzer, Align GV-GD, and REVEL (Table 4 and Table 5 ). To assess the performance of eight different stability predictor programs (DUET, SDM, mCSM, I-Mutant3.0, MUpro, iPTREE-STAB, CUPSAT, and iStable) in predicting the effect of missense mutations on PITX2 protein stability, the change in protein stability (ΔΔG) were computed for all 24 PITX2 homeodomain variants (15 functionally characterised and 9 functionally uncharacterised mutations) (Table 7) . cache = ./cache/cord-002973-bkr4ndl2.txt txt = ./txt/cord-002973-bkr4ndl2.txt === reduce.pl bib === id = cord-000003-ejv2xln0 author = Crouch, Erika C title = Surfactant protein-D and pulmonary host defense date = 2000-08-25 pages = extension = .txt mime = text/plain words = 6799 sentences = 330 flesch = 38 summary = SP-D, a collagenous calcium-dependent lectin (or collectin), binds to surface glycoconjugates expressed by a wide variety of microorganisms, and to oligosaccharides associated with the surface of various complex organic antigens. The phenotype of macrophages isolated from the lungs of SP-D-deficient mice is altered, and there is circumstantial evidence that abnormal oxidant metabolism and/or increased metalloproteinase expression contributes to the development of emphysema. The potential consequences of this interaction include the following: varying degrees of lectin-dependent aggregation (namely, microbial agglutination), enhanced binding of microorganisms or microbial aggregates to their 'receptors' on host cells, phagocyte activation, and opsonic enhancement of phagocytosis and killing, potentially involving one or more cellular receptors for SP-D. Although the protein has been immunolocalized to alveolar macrophage membranes and distributes together with SP-D in many different human tissues [10 • ,77], it has not yet been shown to mediate the binding of SP-D to these cells or to participate in signal transduction events. cache = ./cache/cord-000003-ejv2xln0.txt txt = ./txt/cord-000003-ejv2xln0.txt === reduce.pl bib === id = cord-005145-1l87fdmi author = Marquet-Blouin, E. title = Neutralizing immunogenicity of transgenic carrot (Daucus carota L.)-derived measles virus hemagglutinin date = 2003 pages = extension = .txt mime = text/plain words = 5640 sentences = 282 flesch = 49 summary = Despite differences in post-translational processing viral and bacterial antigens preserved their immunogenic properties when produced in plants and induced cross-reactive and sometimes neutralizing and protective antibodies. The aim of this study was (1) to explore the potential of carrots as an expression system for antigens that is suitable for human consumption, and (2) to test whether the measles virus hemagglutinin glycoprotein would preserve its neutralizing immunogenicity in this system. Although some work has been done with transgenic carrot callus cells (Brodzik et al., 2000) , this is one of the first reports of the expression of a transgenic antigen in mature carrots, showing that high levels of virus-neutralizing antibodies can be induced with a glycoprotein produced in this plant. The flow cytometry data showed that all mice vaccinated with transgenic leaf or root extracts produced high levels of antibodies cross-reacting with the native protein independently whether virus-infected or H-protein transfected cells were used. Plant-derived measles virus hemagglutinin protein induces neutralizing antibodies in mice cache = ./cache/cord-005145-1l87fdmi.txt txt = ./txt/cord-005145-1l87fdmi.txt === reduce.pl bib === id = cord-000479-u87eaaj8 author = Stolf, Beatriz S. title = Protein Disulfide Isomerase and Host-Pathogen Interaction date = 2011-10-11 pages = extension = .txt mime = text/plain words = 5990 sentences = 297 flesch = 41 summary = These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intraand interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. Among the many redox sensitive proteins that are altered during the course of different infections, protein disulfide isomerase (PDI-) mediated redox switches have been associated with pathogen attachment-internalization, antigen processing in the ER/phagosome, and the regulation of ROS production by Nox family enzymes. PDI is thought to attach to lipids, glycans, and integral membrane proteins via electrostatic interactions at the cell plasma membrane [14, 15] , where its reductive activity mediates the infection of different pathogens ( Figure 2 , discussed later). Protein disulfide isomerase (PDI) associates with NADPH oxidase and is required for phagocytosis of Leishmania chagasi promastigotes by macrophages cache = ./cache/cord-000479-u87eaaj8.txt txt = ./txt/cord-000479-u87eaaj8.txt === reduce.pl bib === === reduce.pl bib === id = cord-014685-ihh30q6f author = nan title = Posters P788 - P999 date = 2005-09-21 pages = extension = .txt mime = text/plain words = 38354 sentences = 1784 flesch = 45 summary = This study has attempted to analyse the structural properties of membrane peptides and proteins through the use of model systems that have been designed to mimic their natural counterparts: Podlubnaya 2 1 Institute of Theoretical and Experimental Biophysics RAS, 2 Pushchino State University Amyloid brils are formed by proteins or their peptides in the result of a conformational transition from alpha helix into beta-sheet structure. Analysis of the results of such studies indicate that folding of SNase fragments is dominated by developing the local and non-local nucleation sites from native-like secondary structures and by intensifying the longrange interactions of residues at nucleation sites with residues further removed in sequence. The results show that at different pH values the aggregation processes of both proteins follow different pathways determined by the variations in the native structure and by the details of the involved conformational changes. cache = ./cache/cord-014685-ihh30q6f.txt txt = ./txt/cord-014685-ihh30q6f.txt === reduce.pl bib === === reduce.pl bib === id = cord-014852-6friw2ek author = Chumakov, S. P. title = Organization and regulation of nucleocytoplasmic transport date = 2010-04-24 pages = extension = .txt mime = text/plain words = 9153 sentences = 496 flesch = 50 summary = Nuclear RanGTP is capable of releasing the target protein from an imported complex upon binding with karyo pherins. The main properties that allow karyopherins to ensure efficient nuclear transport are their capabilities of binding with a target protein (directly or through an adaptor) and interacting with Nup or RanGTP [12] . Structural studies of karyopherin β1 in complex with the phenylalanine-glycine (FG) repeat contain ing fragment of yeast Nup showed that the interactions between the two proteins are mostly hydrophobic and involve the phenylalanine residues of Nup. The karyo pherin molecule forms two hydrophobic pockets: between HEAT repeats 5 and 6 and between repeats 6 and 7. NTF2 interacts with RanGDP, which is the main cytoplasmic form of Ran. The NTF2-RanGDP complex is transferred into the nucleus, which is due to the ability of NTF2 to interact with low affinity with FG containing Nup proteins, as karyopherins do. One of the key steps of nuclear transport is the interaction of importins and exportins with the NLS or NES of a target protein. cache = ./cache/cord-014852-6friw2ek.txt txt = ./txt/cord-014852-6friw2ek.txt === reduce.pl bib === === reduce.pl bib === id = cord-000575-g1ob16b9 author = Xie, Xiao-li title = Protein sequence analysis based on hydropathy profile of amino acids date = 2012-01-27 pages = extension = .txt mime = text/plain words = 2178 sentences = 116 flesch = 48 summary = A new method to analyze the similarity/dissimilarity of protein sequence was proposed based on the conditional probability of the protein sequence. Based on the graphical representation, it is possible to numerically characterize DNA sequence and further quantitatively measure similarity of different DNA sequences. This is mainly because extension of DNA graphical representation to protein sequences would enormously increase the number of possible alternative assignments for the 20 amino acids. The graphical representation of protein sequence cannot only describe amino acid sequence, but also measure similarity/ dissimilarity of different protein sequences. In this paper, we converted a protein sequence into three-letter sequence based on hydropathy profile of amino acid and defined the three curves to represent different hydropathy features. The method is based on the graphical representation and conditional probability taken as the numerical characterization of the protein sequence. Similarity/dissimilarity studies of protein sequences based on a new 2D graphical representation cache = ./cache/cord-000575-g1ob16b9.txt txt = ./txt/cord-000575-g1ob16b9.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-008556-oetrdm8g author = Kozak, Marilyn title = Regulation of Protein Synthesis in Virus-Infected Animal Cells date = 2008-03-01 pages = extension = .txt mime = text/plain words = 23945 sentences = 1270 flesch = 51 summary = One consequence of the scanning mechanism is that deleting the "ribosome binding site" (i.e., the normal initiator codon and flanking sequences) will not abolish translation; ribosomes will simply use the next AUG codon downstream, which, in some cases, has been shown to direct the synthesis of a biologically active, truncated protein (Downey et al., 1984; Halpern and Smiley, 1984; Katinka and Yaniv, 1982) . The best evidence for this is the ability of both EMC and SFV 26 S mRNA to be translated in EMC virus-infected cells, in which host translation is drastically inhibited by a mechanism that has not been difined, but that clearly does not involve cap binding protein (Mosenkis et al., 1985) . In wild-type adenovirus-infected cells, in which host protein synthesis is drastically reduced, both adenovirus and influenza virus mRNAs are translated efficiently. cache = ./cache/cord-008556-oetrdm8g.txt txt = ./txt/cord-008556-oetrdm8g.txt === reduce.pl bib === id = cord-000372-wzwpyvll author = Castelló, Alfredo title = The Multifaceted Poliovirus 2A Protease: Regulation of Gene Expression by Picornavirus Proteases date = 2011-04-14 pages = extension = .txt mime = text/plain words = 16333 sentences = 781 flesch = 45 summary = These findings are in agreement with the fact that host mRNA transcription takes place in 2A pro -expressing cells when both translation and RNA nuclear export are inhibited, upon cleavage of eIF4G and Nups [17] . In this regard, PV 2A pro has been very useful for examining the requirements for eIF4G to translate different cellular or viral mRNAs. In addition to this, in this paper, we have highlighted the role of PV 2A pro not only in the processing of the poliovirus polyprotein but also in the interaction with the host-cell. In particular, PV 2A pro cleaves cell proteins involved in transcription, pre-mRNA splicing, nucleus/cytoplasm transport and translation, in order to hijack those host functions and to concentrate the cellular resources on the production of the viral progeny. cache = ./cache/cord-000372-wzwpyvll.txt txt = ./txt/cord-000372-wzwpyvll.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-014901-d9szap94 author = Permyakova, N. V. title = State of research in the field of the creation of plant vaccines for veterinary use date = 2015-01-04 pages = extension = .txt mime = text/plain words = 8091 sentences = 343 flesch = 41 summary = Transgenic plants as an alternative of costly systems of recombinant immunogenic protein expression are the source for the production of cheap and highly efficient biotherapeuticals of new generation, including plant vaccines. Of principal importance of this work development was the creation of the "edible vaccine" concept, the essence of which is the use of genetically modified plants containing protein anti gens of infectious agents for oral delivery of relevant antigens to the mucosa of the gastrointestinal tract of warm blooded animals. Preparation of medicinal substances for the pro duction of veterinary products is based on various approaches, including biotechnology using genetically modified (transgenic) organisms for these purposes; such expression systems as bacteria, yeast, cells of insects and mammals are used. This review is devoted to the analysis of possibilities of producing recombinant immunogenic proteins for veterinary use on the basis of plant expression systems, and the history of the concept of "edible vaccines" for animal immunization. cache = ./cache/cord-014901-d9szap94.txt txt = ./txt/cord-014901-d9szap94.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-003435-ke0az7nf author = Schlake, Thomas title = mRNA as novel technology for passive immunotherapy date = 2018-10-17 pages = extension = .txt mime = text/plain words = 15190 sentences = 850 flesch = 40 summary = Recombinant technologies further expanded the available therapies based on mAbs. In vitro antibody selection technologies like phage or ribosome display were developed to enable the generation of highly specific human mAbs out of libraries that may even be naïve for the specific antigens [31] [32] [33] [34] [35] [36] 1 Schematic illustration comparing active immunization and passive antibody immunotherapies. While T cell engineering for adoptive transfer inevitably requires the use of nucleic acids encoding a target-specific receptor, antibody immunotherapy can deploy recombinant proteins. However, the effects of mRNA modifications on translation, immunostimulation and resulting protein expression appear to be variable, for instance dependent on the type of target cells. In comparison to a single transfer of cells with retroviral CAR expression, an mRNA-encoded receptor required three consecutive lymphocyte infusions to obtain a comparable antitumor effect [262] . cache = ./cache/cord-003435-ke0az7nf.txt txt = ./txt/cord-003435-ke0az7nf.txt === reduce.pl bib === === reduce.pl bib === id = cord-004584-bcw90f5b author = nan title = Abstracts: 8th EBSA European Biophysics Congress, August 23rd–27th 2011, Budapest, Hungary date = 2011-08-06 pages = extension = .txt mime = text/plain words = 106850 sentences = 5038 flesch = 41 summary = Our goals are two-fold: (1) to monitor conformational changes in each domain upon its binding to specific ligands and then to correlate the observed changes with structural differences between the CRDs and (2) to investigate the interaction between the CRDs and lipid model membranes. Cholesterol-assisted lipid and protein interactions such as the integration into lipid nanodomains are considered to play a functional part in a whole range of membrane-associated processes, but their direct and non-invasive observation in living cells is impeded by the resolution limit of [200nm of a conventional far-field optical microscope. Therefore, to investigate the dynamic and complex membrane lateral organization in living cells, we have developed an original approach based on molecule diffusion measurements performed by fluorescence correlation spectroscopy at different spatial scales (spot variable FCS, svFCS) (1). cache = ./cache/cord-004584-bcw90f5b.txt txt = ./txt/cord-004584-bcw90f5b.txt === reduce.pl bib === id = cord-016594-lj0us1dq author = Flower, Darren R. title = Identification of Candidate Vaccine Antigens In Silico date = 2012-09-28 pages = extension = .txt mime = text/plain words = 12570 sentences = 653 flesch = 37 summary = In the wider context of the experimental discovery of vaccine antigens, with particular reference to reverse vaccinology, this chapter adumbrates the principal computational approaches currently deployed in the hunt for novel antigens: genome-level prediction of antigens, antigen identification through the use of protein sequence alignment-based approaches, antigen detection through the use of subcellular location prediction, and the use of alignment-independent approaches to antigen discovery. When looking at a reverse vaccinology process, the discovery of candidate subunit vaccines begins with a microbial genome, perhaps newly sequence, progresses through an extensive computational stage, ultimately to deliver a shortlist of antigens which can be validated through subsequent laboratory examination. Conventional empirical, experimental, laboratory-based microbiological ways to identify putative candidate antigens require cultivation of target pathogenic micro-organisms, followed by teasing out their component proteins, analysis in a series of in-vitro and in-vivo assays, animal models and with the ultimate objective of isolating one or two proteins displaying protective immunity. cache = ./cache/cord-016594-lj0us1dq.txt txt = ./txt/cord-016594-lj0us1dq.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-006331-s2qf98lj author = Spiridonova, V. A. title = Molecular recognition elements: DNA/RNA-aptamers to proteins date = 2010-05-23 pages = extension = .txt mime = text/plain words = 7144 sentences = 412 flesch = 57 summary = After 16 rounds of selection from the 2' amino modified RNA library the isolated aptamers formed a complex with FVIIa characterized by the K d value of 11.3 ± 1.3 nM. performed RNA selection to FIXa; after eight rounds of selection they found an aptamer, which bound to FIXa with the K d value of 0.65 ± 0.2 nM and exhibited 5000 fold higher affinity to FIXa compared with FVIIa, FXa, FXIa and activated protein C [20] . These aptamers formed a complex with ΔNS3 with the K d value of 10 nM, caused 90% inhibition of protease activity of the ΔNS3 peptide and full sized NS3 bound to a maltose binding protein (MBP NS3). Four teen rounds of selection yielded the RNA aptamer, exhibiting high affinity binding to p50 and inhibition of NF kB binding to DNA by preventing protein dimerization [91] . cache = ./cache/cord-006331-s2qf98lj.txt txt = ./txt/cord-006331-s2qf98lj.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-017326-1caeui30 author = Seay, Montrell title = Digesting Oneself and Digesting Microbes: Autophagy as a Host Response to Viral Infection date = 2005 pages = extension = .txt mime = text/plain words = 11363 sentences = 489 flesch = 34 summary = Genetic studies in yeast and mammalian cells have also shown that the eIF2 kinase signaling pathway is required for starvation and herpes simplex virus-induced autophagy 18 . The role of some of the Atg proteins, including ones that act in the lipid kinase signaling complex and in the ubiquitin-like conjugation pathways, has been studied in plant and mammalian viral infections (see Table 1 ). Together, the studies of Sindbis virus infection in neurons overexpressing beclin 1 or in cultured cells lacking beclin 1 or atg5 demonstrate a role for mammalian autophagy genes in both restricting viral replication and in protection against virus-induced cell death. The interferon-inducible, antiviral PKR signaling pathway positively regulates autophagy, and both mammalian and plant autophagy genes restrict viral replication and protect against virus-induced cell death. The interferon-inducible, antiviral PKR signaling pathway positively regulates autophagy, and both mammalian and plant autophagy genes restrict viral replication and protect against virus-induced cell death. cache = ./cache/cord-017326-1caeui30.txt txt = ./txt/cord-017326-1caeui30.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-010681-tmpxs9og author = Dondapati, Srujan Kumar title = Cell-Free Protein Synthesis: A Promising Option for Future Drug Development date = 2020-03-20 pages = extension = .txt mime = text/plain words = 10674 sentences = 487 flesch = 36 summary = aatRNA aminoacyl-tRNA, AAS aminoacyl-tRNA synthetase, ATP adenosine triphosphate, EF elongation factor, GSH glutathione, GSSG glutathione-disulfide, GTP guanosine-5'-triphosphate, IF initiation factor, IRES internal ribosome entry site, MP membrane protein, nCAA non-canonical amino acid, PDI protein disulfide isomerase, PEG polyethylene glycol, PTM post-translational modification, R ribosomes, t-RNA transfer RNA, TF transcription factor, UTR untranslated region, VLP virus like particle Chinese hamster ovary (CHO) Mimic the CHO cell-based production PTMs (N-glycosylation, disulfide bridging, and lipidation) Suitable for a wide range of eukaryotic and complex proteins Presence of translational active endogenous microsomes [45] High yields in CECF mode Endotoxin free Lysates used for point-of-care testing [30] Low yields especially in the batch mode [58] Cost ineffective and difficult to establish unlike E. cache = ./cache/cord-010681-tmpxs9og.txt txt = ./txt/cord-010681-tmpxs9og.txt === reduce.pl bib === id = cord-016448-7imgztwe author = Frishman, D. title = Protein-protein interactions: analysis and prediction date = 2009-10-01 pages = extension = .txt mime = text/plain words = 18354 sentences = 912 flesch = 39 summary = In general, investigating the topology of protein interaction, metabolic, signaling, and transcriptional networks allows researchers to reveal the fundamental principles of molecular organization of the cell and to interpret genome data in the context of large-scale experiments. The basic principle is fairly simple and rests implicitly on a multigraph representation: several interaction networks to be integrated, each resulting from a specific experimental or predictive method, are defined over the same set of proteins. This software provides functionalities for (i) generating biological networks, either manually or by importing interaction data from various sources, (ii) filtering interactions, (iii) displaying networks using graph layout algorithms, (iv) integrating and displaying additional information like gene expression data, and (v) performing analyses on networks, for instance, by calculating topological network properties or by identifying functional modules. The evidence can be derived from literature mining, functional associations based on Gene Ontology annotations, co-occurrence of transcriptional motifs, correlation of expression data, sequence similarity, common protein domains, shared metabolic pathway membership, and protein-protein interactions. cache = ./cache/cord-016448-7imgztwe.txt txt = ./txt/cord-016448-7imgztwe.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-014661-mrh2pbi6 author = Dumitrascu, Georgiana R. title = Critical physiological and pathological functions of Forkhead Box O tumor suppressors date = 2013-12-31 pages = extension = .txt mime = text/plain words = 9235 sentences = 419 flesch = 38 summary = FOXO proteins are considered unique cellular targets, regulating a wide variety of critical cellular processes, such as: apoptosis, oxidative stress, DNA damage repair, cell cycle, stem cell proliferation and maintenance, metabolism, angiogenesis, vascular tone, cardiovascular development, fertility, immune response and neuronal survival 4, 20 . Hence, the FOXO transcription factors control the expression of a wide spectrum of genes that regulate essential physiological cellular processes, such as cell death/cell survival, cell cycle, cell proliferation, cell differentiation/development, angiogenesis, cell metabolism, stress response and stem cell maintenance 33,34,35,36,37,38 (Figure 2) . Moreover, the consensus FOXO recognition element (FRE) -(G/C)(T/A)AA(C/T)AA -which differs from that of other forkhead proteins, seems to have a very important role in both apoptotic pathways, since matching functional FRE sites have been identified in the promoters of FOXO target genes encoding Fas ligand (FasL), insulin like growth factorbinding protein 1 (IGFBP1), the apoptotic regulator Bcl-2 interacting mediator of cell death (Bim) and others 30 . cache = ./cache/cord-014661-mrh2pbi6.txt txt = ./txt/cord-014661-mrh2pbi6.txt === reduce.pl bib === === reduce.pl bib === id = cord-006636-xgikbdns author = Ühlein, E. title = Übersicht Über neue ernährungswissenschaftliche Publikationen date = 1964-02-01 pages = extension = .txt mime = text/plain words = 31038 sentences = 4914 flesch = 58 summary = L. : Effect of a low dietary level of three types of fat on reproductive performance and tissue lipid content of the vitamin B6-deficicnt female rat. H.: Effect of dietary protein and fat on growth, protein utilization, and carcass composition of pigs fed purified diets. Effect of food fats on concentration of ketone bodies and citric acid level in blood and tissues Effect of a low dietary level of three types of fat on reproductive performance and tissue lipid content of the vitamin B6-defieient female rat The effect on the serum cholesterol levels of the consumption of a special dietary fat with a high content of unsaturated fatty acids in elderly people Effect of protein intake and cold exposure on selected liver enzymes associated with amino acid metabolism Effect of protein intake and cold exposure on selected liver enzymes associated with amino acid metabolism cache = ./cache/cord-006636-xgikbdns.txt txt = ./txt/cord-006636-xgikbdns.txt === reduce.pl bib === id = cord-010938-12igesqw author = Patra, Prasanta title = Epitope-Based Vaccine Designing of Nocardia asteroides Targeting the Virulence Factor Mce-Family Protein by Immunoinformatics Approach date = 2019-08-21 pages = extension = .txt mime = text/plain words = 4628 sentences = 284 flesch = 47 summary = title: Epitope-Based Vaccine Designing of Nocardia asteroides Targeting the Virulence Factor Mce-Family Protein by Immunoinformatics Approach Appropriate structural identity of the virulence factor Mce-family protein generated through Phyre2 server and subsequently validated by ProSA and PROCHECK program suite. Consequently the targeted protein sequence has been crucially analyzed through several authentic web prediction portals focus to extract the functional epitopes leading to narrative vaccine generation against Nocardiosis disease. The server utilizes recurrent neural network technique to locate the specific B-cell epitopes present in targeted protein sequence. Amino acid sequence of virulence factor Mce-family protein has been submitted to the server and a zip file containing predictions is comes out as systematic result component. ABCpred server predicts 20 linear epitopes (Table 1) within the virulence factor Mce-family protein of 20 amino The structural profile of virulence factor Mce family protein also been mapped out via Phyre2 server that will be fundamental for therapeutics to design the vaccine. cache = ./cache/cord-010938-12igesqw.txt txt = ./txt/cord-010938-12igesqw.txt === reduce.pl bib === === reduce.pl bib === id = cord-016419-v1f6dx3e author = Gupta, Varsha title = Production of Recombinant Pharmaceutical Proteins date = 2016-10-23 pages = extension = .txt mime = text/plain words = 9648 sentences = 602 flesch = 50 summary = Usage of recombinant DNA technology for large-scale production of proteins requires ample amount of time, labor, and resources, but it also offers many opportunities for economic growth. The recombinant proteins approved by FDA are obtained either from Escherichia coli or other prokaryotes; from Saccharomyces cerevisiae or other fungal species; from insect cells , mammalian cells , or human cells ; or from transgenic plants or animals. Their advantages are low cost, high mass production, scale-up, lack of human pathogens , and addition of eukaryotic PTMs. The fi rst recombinant protein obtained in 1986 from tobacco plants was human growth hormone . The vector can be modifi ed to express genes for insulin (tomato) or Hep-B surface antigen (HBsAg) for recombinant therapeutics providing a human glycosylation pattern have increased attention, and the efforts are being made for the development of novel glycoengineered cell lines for production of fully glycosylated protein therapeutic. cache = ./cache/cord-016419-v1f6dx3e.txt txt = ./txt/cord-016419-v1f6dx3e.txt === reduce.pl bib === id = cord-014462-11ggaqf1 author = nan title = Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh date = 2011-04-21 pages = extension = .txt mime = text/plain words = 35453 sentences = 1711 flesch = 49 summary = Molecular diagnosis based on reverse transcription (RT)-PCR s.a. one step or nested PCR, nucleic acid sequence based amplification (NASBA), or real time RT-PCR, has gradually replaced the virus isolation method as the new standard for the detection of dengue virus in acute phase serum samples. Non-genetic methods of management of these diseases include quarantine measures, eradication of infected plants and weed hosts, crop rotation, use of certified virus-free seed or planting stock and use of pesticides to control insect vector populations implicated in transmission of viruses. The results of this study indicate that NS1 antigen based ELISA test can be an useful tool to detect the dengue virus infection in patients during the early acute phase of disease since appearance of IgM antibodies usually occur after fifth day of the infection. The studies showed high level of expression in case of constructed vector as compared to infected virus for the specific protein. cache = ./cache/cord-014462-11ggaqf1.txt txt = ./txt/cord-014462-11ggaqf1.txt === reduce.pl bib === === reduce.pl bib === id = cord-016095-jop2rx61 author = Vignais, Pierre V. title = Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century date = 2010-06-08 pages = extension = .txt mime = text/plain words = 42843 sentences = 1503 flesch = 43 summary = Instead of setting out to discover unknown mechanisms by analyzing effects that are dependent on specific causes, with some uncertainty as to the possible success of the enterprise being undertaken, which is the foundation stone of the Bernardian paradigm of the experimental method, many current research projects give themselves achievable and programmable objectives that depend upon the means available to them: sequencing of genomes with a view to comparing them, recognition of sequence similarities in proteins coded for by genes belonging to different species, with the aim of putting together phylogenetic trees, synthesis of interesting proteins in transgenic animals and plants, analysis of the three-dimensional structure of proteins, in order to find sites that are likely to fix medicinal substances, and synthesis of molecular species able to recognize pathogenic targets. cache = ./cache/cord-016095-jop2rx61.txt txt = ./txt/cord-016095-jop2rx61.txt === reduce.pl bib === === reduce.pl bib === id = cord-014597-66vd2mdu author = nan title = Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017 date = 2018-03-15 pages = extension = .txt mime = text/plain words = 50613 sentences = 2624 flesch = 46 summary = Irrespective of the cell culture-based system and production scale, PEIpro® and PEIpro®-HQ have led to efficient viral vector yields superior to 10 7 IG/mL and 10 9 VG/mL, respectively for lentiviruses and AAVs Background Continuous perfusion process is making a comeback as a competing upstream manufacturing technology for the production of Biopharmaceuticals compared to the standard fed batch processes. To evaluate the impact of feed-spiking compared with cultivation in basal medium only, the cell line was grown in bioreactors under controlled conditions to determine cellspecific metabolic rates, nutrient consumption, and byproduct accumulation over the process time. Through the interchangeability of signal peptides between products and even species, a large variety can be used to enhance protein expression in already existing production systems Materials and methods At first the influence of four different natural SPs (SP (7), (8), (9) and (10)) was compared on the secreted amount of an IgG4 model antibody (product A) in fed batches using a CHO DG44 host cell line. cache = ./cache/cord-014597-66vd2mdu.txt txt = ./txt/cord-014597-66vd2mdu.txt === reduce.pl bib === id = cord-017887-pj6pal35 author = OuYang, Bo title = Structural and Functional Properties of Viral Membrane Proteins date = 2018-06-29 pages = extension = .txt mime = text/plain words = 11512 sentences = 560 flesch = 48 summary = Functional mutagenesis studies have suggested that, at least in the cases of HIV-1 and influenza A viruses, the TM domains (TMDs) of fusion proteins are not merely membrane anchors, but play important roles in membrane fusion and viral infectivity. Apart from the channels and fusion proteins, some viruses have developed enzymatic domains anchored to the membrane, e.g., the polymerases of the hepatitis C virus and the neurominidase of the influenza viruses. Unlike many other broad-spectrum antivirals, Arbidol has an established mechanism of action against the HAs in influenza A and B viruses that involves the inhibition of virus-mediated membrane fusion and thus viral entry [50] . The NMR structure of the HIV-1 Env TMD may provide some clues for how other viral fusion proteins oligomerize in the membrane. Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes cache = ./cache/cord-017887-pj6pal35.txt txt = ./txt/cord-017887-pj6pal35.txt === reduce.pl bib === id = cord-017866-h5ttoo0z author = Bowman, Grant R. title = Biogenesis of Dense-Core Secretory Granules date = 2010-05-27 pages = extension = .txt mime = text/plain words = 13369 sentences = 678 flesch = 42 summary = For such regulated exocytosis, the vesicles that carry newly-synthesized protein from the TGN accumulate in the cytoplasm until specific extracellular events trigger their fusion with the plasma membrane, resulting in the release of vesicle contents.f The vesicles involved are called dense-core granules (DCGs), the name reflecting the fact that the contents are so highly condensed that they form a large electron-dense plug in the vesicle lumen. In support of this hypothesis, recent studies have suggested that prohormone convertases 1 and 2, which are responsible for proteolytic cleavageof lumenal proteins during granule maturation, are sorted to ISGs by virtue of C-terminal membrane raft-associated tails, which are by themselves necessary and sufficient for targeting to DCGs,uo 120 Additionally, cytoplasmic signals on some transmembrane proteins appear to play important roles in sorting, but the mechanisms are unknown. cache = ./cache/cord-017866-h5ttoo0z.txt txt = ./txt/cord-017866-h5ttoo0z.txt === reduce.pl bib === === reduce.pl bib === id = cord-004879-pgyzluwp author = nan title = Programmed cell death date = 1994 pages = extension = .txt mime = text/plain words = 81677 sentences = 4465 flesch = 51 summary = Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. cache = ./cache/cord-004879-pgyzluwp.txt txt = ./txt/cord-004879-pgyzluwp.txt === reduce.pl bib === === reduce.pl bib === id = cord-018647-bveks6t1 author = Butnariu, Monica title = Plant Nanobionics: Application of Nanobiosensors in Plant Biology date = 2019-10-01 pages = extension = .txt mime = text/plain words = 16812 sentences = 779 flesch = 40 summary = Chemical or biological NBS functions on the principle of signal emission (voltage or electrical, photonic) in response to a chemical reaction involve a chemical or biological receptor, R (macrocyclic ligand, antibody enzyme), that binds to a specific target molecule of a sample to be studied, the analyte, A. Analysis of signals in plant nanobionics aims at processing signals recorded by measurements in order to extract the maximum of useful information for diagnostics and These devices are mostly used in genetic engineering in agriculture, where it is necessary to know the mechanisms of reaction and the affinity of enzymes and microorganisms for different substrates of interest and signaling molecules. The reaction is monitored by an integrated detector (transducer) that measures the stationary or transition states or the final reaction product via the immobilized biocidal product in NBSs. Types of commonly used biocatalysts are enzymes (simple or enzymatic complexes)-most commonly used as recognition systems, cells, microorganisms (bacteria, fungi, eukaryotic cells, or yeasts), cellular organs, or component (cell walls, mitochondria) sections of plant or animal tissues. cache = ./cache/cord-018647-bveks6t1.txt txt = ./txt/cord-018647-bveks6t1.txt === reduce.pl bib === id = cord-017817-ztp7w9yh author = Land, Walter Gottlieb title = Cell-Autonomous (Cell-Intrinsic) Stress Responses date = 2018-03-28 pages = extension = .txt mime = text/plain words = 17727 sentences = 855 flesch = 40 summary = Autophagy is an evolutionarily highly conserved self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components such as defective/damaged or redundant organelles or protein aggregates are delivered to the lysosome for recycling and degradation. More recent studies then revealed that these transcription factors, notably Nrf2, are activated by Keap1 as the primary negative regulator of Nrf2, that is, a molecule that simultaneously operates as a sensor protein able to perceive dyshomeostatic Subclass IIC-4 DAMPs, for example, in terms of redox changes reflecting electrophilic stress. Strikingly, a complex relationship reportedly exists between autophagy and DAMPs in cellular adaption to stress and injury and cell death characterized by a crosstalk between autophagy induction and secretion or release of DAMPs. In fact, growing evidence indicates that autophagic mechanisms are involved in regulating release and degradation of DAMPs including CALR, HMGB1, ATP, and DNA in several cell types [37, 148, 175] . cache = ./cache/cord-017817-ztp7w9yh.txt txt = ./txt/cord-017817-ztp7w9yh.txt === reduce.pl bib === id = cord-018479-mvnm98hv author = Rehm, Fabian B. H. title = Applications of Microbial Biopolymers in Display Technology date = 2017-11-16 pages = extension = .txt mime = text/plain words = 4621 sentences = 227 flesch = 35 summary = Such beads have been demonstrated in diverse applications, including fluorescence-activated cell sorting, enzyme-linked immunosorbent assays, microarrays, diagnostic skin test for tuberculosis, vaccines, protein purification, and affinity bioseparation. Most recently, PHA inclusions with GFP and MOG fused to PhaP or PhaC, such that each granule is simultaneously displaying two protein-based functionalities, were examined in the context of FACS, providing proof-of-concept for the biotechnological application of bifunctional PHA beads which may extend beyond FACS ). This study demonstrated that V HH domains from camelid antibodies, designed ankyrin repeat proteins (DARPins) and OB-folds (OBodies), could be densely displayed on PHA beads resulting in high affinity binding resins for purification of various target proteins. Overall, PhaC engineering such as N-or C-terminal fusions and/or insertions enabled efficient display of binding domains for interaction with target compounds resulting in purification performance suitable for application as bioseparation resin. cache = ./cache/cord-018479-mvnm98hv.txt txt = ./txt/cord-018479-mvnm98hv.txt === reduce.pl bib === === reduce.pl bib === id = cord-018265-twp33bb6 author = Becker, Pablo D. title = Community-acquired pneumonia: paving the way towards new vaccination concepts date = 2007 pages = extension = .txt mime = text/plain words = 14121 sentences = 697 flesch = 36 summary = A live vaccine based on a master virus strain developed at the Institute of Applied Microbiology (Austria) by growing wild influenza virus in Vero cells at 25°C was also demonstrated to be safe, well-tolerated and immunogenic after intranasal immunization in young adults [18]. Candidate vaccines should be able to replicate and induce a protective immune response in young infants, even in the presence of maternally acquired antibodies. This demonstrates that antibodies play a major role in protection against this disease, whereas T-cell immunity targeted to internal viral proteins appears to contribute to clearance. The second generation of PS-based conjugate vaccines stimulates stronger antibody responses, even in infants, young children and immune deficient individuals, as well as immunological memory. The resulting proteins are then used to perform immunological and/or functional studies to select the most promising candidates (e.g., able to induce the production of microbicidal or neutralizing antibodies, capacity to confer protective immunity). cache = ./cache/cord-018265-twp33bb6.txt txt = ./txt/cord-018265-twp33bb6.txt === reduce.pl bib === id = cord-018018-2yyv8vuy author = Rybicki, Ed title = History and Promise of Plant-Made Vaccines for Animals date = 2018-07-04 pages = extension = .txt mime = text/plain words = 9127 sentences = 314 flesch = 37 summary = 1995) was also used to demonstrate the efficacy of two very different plant-made papillomavirus vaccines, a few years after the demonstration that Human papillomavirus L1 major capsid protein virus-like particles could be produced in transgenic tobacco or potato (Biemelt et al. The early historical account of molecular farming for veterinary vaccines given above gives an idea of the array of technologies available and used up to the mid-2000s: transgenic and transplastomic expression of subunit proteins; recombinant plant viruses either used to express whole vaccine candidate genes, or to display chosen peptides fused to their capsid proteins; fusion of vaccine protein genes to carrier proteins to improve immunogenicity, including by inherent adjuvant properties; candidate parenteral and oral vaccines to both viruses and bacteria; therapeutics for animals made in plants; use of plant cell cultures to make antigens. cache = ./cache/cord-018018-2yyv8vuy.txt txt = ./txt/cord-018018-2yyv8vuy.txt === reduce.pl bib === id = cord-018969-0zrnfaad author = Giese, Matthias title = Types of Recombinant Vaccines date = 2015-09-24 pages = extension = .txt mime = text/plain words = 14221 sentences = 811 flesch = 48 summary = New vaccines and vaccination strategies are being developed including the use of attenuated live mycobacteria, recombinant microorganisms, and subunits, prime-boost strategies based on the successive administration of a certain mycobacterial antigen under two different vaccine vectors, and DNA vaccines [ 1 ] . However, several animal models have been developed to study the pathogenesis of Shigella , the resulting immune response against Shigella antigens, and the protection efficacy of candidate vaccines against shigellosis: [ 31 ] . The GAS M protein is the major protective antigen and an ideal target for vaccine development; however it contains heart tissue cross-reactive epitopes particularly in the conserved region [ 98 ] . Immunization of mice with a C-region peptide GAS vaccine candidate called J8 conjugated to the carrier protein diphtheria toxoid (dT) and co-delivery with an appropriate adjuvant led to protection against systemic and mucosal GAS infection [ 104 ] (Fig. 9.29 ). cache = ./cache/cord-018969-0zrnfaad.txt txt = ./txt/cord-018969-0zrnfaad.txt === reduce.pl bib === id = cord-021626-ck2kybtp author = Walker-Smith, John title = Dietary protein intolerance date = 2013-10-21 pages = extension = .txt mime = text/plain words = 13881 sentences = 727 flesch = 50 summary = Abnormalities of the small intestinal mucosa have been reported in children suffering temporary intolerances to cows' milk protein, soy protein, gluten, eggs, chicken, ground rice and fish. The involvement of IgE in the immunological response of the lamina propria to milk challenge in children with cows' milk protein intolerance has been described by Shiner and her colleagues (1975) , also by Kilby, Walker-Smith and Wood (1976) , who showed an increase in IgE cell numbers in the small intestinal mucosa after a milk challenge in a child with cows' milk sensitive enteropathy. One remarkable exception is the case report of Watt, Pincott and Harries in 1983 of a child with coeliac disease whose small intestinal mucosa was responsive to cows' milk until at least the age of 7 years. In addition to the above challenge procedure, related to small intestinal biopsy, various laboratory tests have been studied to help to diagnose cows' milk protein intolerance. cache = ./cache/cord-021626-ck2kybtp.txt txt = ./txt/cord-021626-ck2kybtp.txt === reduce.pl bib === id = cord-001835-0s7ok4uw author = nan title = Abstracts of the 29th Annual Symposium of The Protein Society date = 2015-10-01 pages = extension = .txt mime = text/plain words = 138514 sentences = 6150 flesch = 40 summary = Altogether, these results indicate that, although PHDs might be more selective for HIF as a substrate as it was initially thought, the enzymatic activity of the prolyl hydroxylases is possibly influenced by a number of other proteins that can directly bind to PHDs. Non-natural aminoacids via the MIO-enzyme toolkit Alina Filip 1 , Judith H Bartha-V ari 1 , Gergely B an oczy 2 , L aszl o Poppe 2 , Csaba Paizs 1 , Florin-Dan Irimie 1 1 Biocatalysis and Biotransformation Research Group, Department of Chemistry, UBB, 2 Department of Organic Chemistry and Technology An attractive enzymatic route to enantiomerically pure to the highly valuable a-or b-aromatic amino acids involves the use of aromatic ammonia lyases (ALs) and aminomutases (AMs). Continuing our studies of the effect of like-charged residues on protein-folding mechanisms, in this work, we investigated, by means of NMR spectroscopy and molecular-dynamics simulations, two short fragments of the human Pin1 WW domain [hPin1(14-24); hPin1(15-23)] and one single point mutation system derived from hPin1(14-24) in which the original charged residues were replaced with non-polar alanine residues. cache = ./cache/cord-001835-0s7ok4uw.txt txt = ./txt/cord-001835-0s7ok4uw.txt === reduce.pl bib === id = cord-004534-jqm1hxps author = nan title = Abstract date = 2009-06-09 pages = extension = .txt mime = text/plain words = 139023 sentences = 6450 flesch = 42 summary = HIV-1 to efficiently complete a replication cycle has to integrate its genome into the host cellular DNA.After HIV-1 enters target cells,neosynthesized viral DNA forms along with other proteins the pre-integration complex (PIC).PICs are then transported into the nucleus where integration,catalyzed by the viral integrase,takes place.HIV-1 viral particles engineered to incorporate integrase fused to EGFP have proven effective to study PICs within nuclei of infected cells.In this study we report the live imaging analysis of nuclear PIC dynamics obtained by time-lapse microscopy.Intranuclear trajectories of IN-EGFP-labeled PIC were collected in three dimensions and examined by both mean squared displacement (MSD) and cage diameter (CD) analysis.In CD the maximum distances measured between two positions occupied by a PIC in a time window of 2 minutes were calculated while in our MSD analysis 5-minute long trajectory segments were considered.Remarkably,MSD revealed the presence of an underlying active transport mechanism.To test the possible role of actin filaments,PIC nuclear trafficking was analyzed in cells treated with latrunculin B (actin polymerization inhibitor).Preliminary results suggest that the disruption of actin function impairs the active nuclear movement of PICs. Second harmonic generation microscopy reveals sarcomere contractile dynamics of cardiomyocytes N. cache = ./cache/cord-004534-jqm1hxps.txt txt = ./txt/cord-004534-jqm1hxps.txt === reduce.pl bib === id = cord-018493-q24f86e9 author = Ranjan, Prabhat title = Importance of Natural Proteins in Infectious Diseases date = 2015-08-08 pages = extension = .txt mime = text/plain words = 3930 sentences = 209 flesch = 39 summary = Other extracellular proteins like invasive enzymes, e.g., coagulase, contributes to the formation of fibrin walls around staphylococcal lesions [10] ; exotoxins (proteins released extracellularly), like neurotoxin (Tetanus toxin, by Clostridium tetani, Botulinum toxin by Clostridium botulinum) [11] and cytotoxins (Diphtheria toxin produced by Corynebacterium dipthereae) [12, 13] , also known as A-B toxins (consisting of 2 subunits: one binds to cell surface receptor and the other is transferred into the cell to damage the cell) [14] , cytolytic toxins (attacking cell constituents causing lysis) like hemolysins produced by Bordetella pertussis, inducing apoptosis of host cells, super antigen toxins (e.g., superantigen, sized 22KDa produced by 5-25 % of Staphylococcus aureus isolates, causing toxic shock syndrome (TSS) by stimulating the release of large amounts of interleukin-1, interleukin-2 and tumor necrosis factor, etc.) [15] . Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are a group of evolutionarily conserved intracellular proteinaceous PRRs that play a vital role in innate immunity and host physiology, in both plants and animals [30, 31] . Heat shock proteins can be expressed on the surface of infected cells, and this is likely to provide a target for the innate immune response. cache = ./cache/cord-018493-q24f86e9.txt txt = ./txt/cord-018493-q24f86e9.txt === reduce.pl bib === id = cord-018437-yjvwa1ot author = Mitchell, Michael title = Taxonomy date = 2013-08-26 pages = extension = .txt mime = text/plain words = 9283 sentences = 561 flesch = 48 summary = Classifi cation is based on the genomic nucleic acid used by the virus (DNA or RNA), strandedness (single or double stranded), and method of replication. The nucleocapsids of some viruses are surrounded by envelopes composed of lipid bilayers and host-or viral-encoded proteins. The sequence of negative-sense ssRNA is complementary to the coding sequence for translation, so mRNA must be synthesized by RNA polymerase, typically carried within the virion, before translation into viral proteins. Among the families of viruses able to infect humans and other vertebrate hosts, there are many species that target and cause disease in the lung. The nucleocapsid is surrounded by an envelope derived from host-cell membrane and viral envelope proteins, including hepatitis B surface antigen. The genome of human parainfl uenza viruses is ~15 kb in length with an organization and six reading frames (N, P, M, F, HN, L) typical of the Paramyxoviridae (Karron and Collins 2007 ) . cache = ./cache/cord-018437-yjvwa1ot.txt txt = ./txt/cord-018437-yjvwa1ot.txt === reduce.pl bib === id = cord-020757-q4ivezyq author = Saikumar, Pothana title = Apoptosis and Cell Death: Relevance to Lung date = 2010-05-21 pages = extension = .txt mime = text/plain words = 7402 sentences = 420 flesch = 39 summary = The extrinsic pathway involves binding of death ligands such as tumor necrosis factor-α (TNF-α), CD95 ligand (Fas ligand), and TNF-related apoptosis-inducing ligand (TRAIL) to their cognate cell surface receptors TNFR1, CD95/Fas, TRAIL-R1, TRAIL-R2, and the DR series of receptors, 29 resulting in the activation of initiator caspase-8 (also known as FADD-homologous ICE/CED-3-like protease or FLICE) and subsequent activation of effector caspase-3 ( Figure 4 .2). In cytotoxic T lymphocyte-induced death, granzyme B, which enters the cell through membrane channels formed by the protein perforin, activates caspases by cleaving them directly or indirectly. Intracellular Pathways: Lack of survival stimuli (withdrawal of growth factor, hypoxia, genotoxic substances, etc.) is thought to generate apoptotic signals through ill-defi ned mechanisms, which lead to translocation of proapoptotic proteins such as Bax to the outer mitochondrial membrane. For example, agents that damage DNA, such as ionizing radiation and certain xenobiotics, lead to activation of p53-mediated mechanisms that commit cells to apoptosis, at least in part through transcriptional upregulation of proapoptotic proteins. cache = ./cache/cord-020757-q4ivezyq.txt txt = ./txt/cord-020757-q4ivezyq.txt === reduce.pl bib === id = cord-022354-aqtceqqo author = HUNTER, ERIC title = Membrane Insertion and Transport of Viral Glycoproteins: A Mutational Analysis date = 2012-12-02 pages = extension = .txt mime = text/plain words = 17747 sentences = 697 flesch = 44 summary = second apolar region in gp 37 consists of a 27 amino acid long stretch of hydrophobic residues near the carboxy terminus that functions during translation to stop the movement of the protein into the lumen of the rough endoplasmic reticulum (RER) and to anchor the complex in the membrane. In order to examine the role of the signal peptide in RSV glycoprotein biosynthesis we constructed a series of deletion mutations within the 5' coding region of the env gene using the double-stranded exonuclease BaBl. Oligonucleotide linkers of the sequence CATCGATG were ligated to the ends of the truncated molecules to introduce a unique restriction endonuclease cleavage site and to replace the deleted in-frame AUG. We found that replacement of the nonconserved region of the cytoplasmic domain with a longer unrelated sequence of amino acids from SV40 vector sequences (mutant Cl) did not alter the rate of transport to the Golgi apparatus nor the appearance of the glycoprotein on the cell surface. cache = ./cache/cord-022354-aqtceqqo.txt txt = ./txt/cord-022354-aqtceqqo.txt === reduce.pl bib === id = cord-022200-hqc8r31t author = HYATT, ALEX D. title = Protein A–Gold: Nonspecific Binding and Cross-Contamination date = 2012-12-02 pages = extension = .txt mime = text/plain words = 3586 sentences = 225 flesch = 56 summary = Some potential problems associated with protein Α -g o l d labeling are also associated with other immunocytochemical techniques, namely nonspecific staining (for example, nonspecific antibodies and electrostatic at tachment; Taylor, 1978; Behnke et al., 1986; Gosselin et al., 1986; Birrell et al., 1987) . In double-labeling experiments cross-contamination is now recognized as a problem which arises from the affinity which protein A possesses for different regions of IgG antibodies, namely the Fc and Fab regions (Roth, 1982; Endresen, 1979; Zikan, 1980) . If the larger of the gold probes is used for the visualization of the first antigen, many potential Fc binding sites (unoccupied protein A) are available for the second immunoglobulin and significant cross-contamination may therefore result. If protein Α-gold is the label, and nonspecific binding and cross-contamination are persistent problems in spite of the addition of excess free protein A, high-affinity stabilizers, adsorption of contaminat ing antibodies, and colloidal gold, then alternative labeling techniques should be pursued and evaluated. cache = ./cache/cord-022200-hqc8r31t.txt txt = ./txt/cord-022200-hqc8r31t.txt === reduce.pl bib === id = cord-021500-sy6lnt7b author = Jean Harry, G. title = Myelination, Dysmyelination, and Demyelination date = 2007-05-09 pages = extension = .txt mime = text/plain words = 17601 sentences = 760 flesch = 37 summary = The size of the fibers and the thickness of the sheaths are very different in the PNS and the CNS, but the overall surface area of myelin generated by an oligodendrocyte around multiple axons may be no larger than that formed by a Schwann cell around a single internode. Myelinating Schwann cells progress through a proliferative "premyelinating" stage, characterized by transient expression of suppressed cAMP-inducible Pou-domain transcription factor (SCIP), followed by a "promyelinating" GalC-positive stage, becoming associated with a single axon in the process. Members of the NDF growth factor family, including glial growth factor (GGF), heregulin, acetylcholine-inducing activity (ARIA), and neuregulin, are alternatively spliced products of a single gene, and these molecules are emerging as important regulators of Schwann cell lineage development (Dong et aL, 1995; Zorick and Lemke, 1996) . cache = ./cache/cord-021500-sy6lnt7b.txt txt = ./txt/cord-021500-sy6lnt7b.txt === reduce.pl bib === id = cord-020101-5rib7pe8 author = nan title = Cumulative Author Index for 2008 date = 2008-11-17 pages = extension = .txt mime = text/plain words = 2140 sentences = 126 flesch = 29 summary = Cauliflower mosaic virus gene VI product N-terminus contains regions involved in resistance-breakage, self-association and interactions with movement protein Intrahost evolution of envelope glycoprotein and OrfA sequences after experimental infection of cats with a molecular clone and a biological isolate of feline immunodeficiency virus DC-SIGN enhances infection of cells with glycosylated West Nile virus in vitro and virus replication in human dendritic cells induces production of Increase in proto-oncogene mRNA transcript levels in bovine lymphoid cells infected with a cytopathic type 2 bovine viral diarrhea virus Complete genome sequence analysis of dengue virus type 2 isolated in Modulation of hepatitis B virus replication by expression of polymerasesurface fusion protein through splicing: Implications for viral persistence Induction of apoptosis in Vero cells by Newcastle disease virus requires viral replication, de-novo protein synthesis and caspase activation Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors cache = ./cache/cord-020101-5rib7pe8.txt txt = ./txt/cord-020101-5rib7pe8.txt === reduce.pl bib === id = cord-020097-eh5deunk author = nan title = Cumulative Author Index for 2006 (Volumes 115–122) date = 2006-10-27 pages = extension = .txt mime = text/plain words = 1481 sentences = 87 flesch = 28 summary = Modulation of PKR activity in cells infected by bovine viral diarrhea virus Complete genome analysis of RFLP 184 isolates of porcine reproductive and respiratory syndrome virus Phylogenetic analysis of the gag region encoding the matrix protein of small ruminant lentiviruses: Comparative analysis and molecular epidemiological applications TATAbinding protein and TBP-associated factors during herpes simplex virus type 1 infection: Localization at viral DNA replication sites Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein Efficient inhibition of hepatitis B virus replication by small interfering RNAs targeted to the viral X gene in mice Preparation and characterization of a novel monoclonal antibody specific to severe acute respiratory syndrome-coronavirus nucleocapsid protein A deletion and point mutation study of the human papillomavirus type 16 major capsid gene Sequencing and comparative analysis of a pig bovine viral diarrhea virus genome Antigenic structure analysis of glycosylated protein 3 of porcine reproductive and respiratory syndrome virus cache = ./cache/cord-020097-eh5deunk.txt txt = ./txt/cord-020097-eh5deunk.txt === reduce.pl bib === id = cord-023740-g84fa45m author = Oldstone, Michael B.A. title = Mimicry by Virus of Host Molecules: Implications for Autoimmune Disease date = 2014-06-27 pages = extension = .txt mime = text/plain words = 2498 sentences = 117 flesch = 41 summary = Monoclonal antibodies against 11 different viruses including DNA and RNA viruses known to cause human infection from the herpes virus group, vaccinia virus, myxoviruses, paramyxoviruses, arenaviruses, flaviviruses, alphaviruses, rhabdovirus, and coronaviruses cross-react with host cell determinants expressed on uninfected tissues. other examples (reviewed in Oldstone and Notkins, 1986 ) suggest a mechanism whereby immune reactants directed against a viral or microbial component may cross-react with a host component and generate autoimmune disease. Since, on the basis of antibody cross-reactivity, many viruses share antigenic sites with normal host cell components, the next step was to look for crossreactive capability in eliciting autoimmunity and related disease. The most likely mechanism by which molecular mimicry would cause disease is by eliciting an immune response against a determinant shared between the host and the virus to bring forth a tissue-specific immune response, presumably capable of destroying cells and eventually the tissue. cache = ./cache/cord-023740-g84fa45m.txt txt = ./txt/cord-023740-g84fa45m.txt === reduce.pl bib === id = cord-006860-a3b8hyyr author = nan title = 40th Annual Meeting of the GTH (Gesellschaft für Thrombose- und Hämostaseforschung) date = 1996 pages = extension = .txt mime = text/plain words = 90660 sentences = 5152 flesch = 50 summary = Dept of Pediatrics, University Hospitals Kiel and Mtinster, Germany Resistance to activated protein C (APCR), in the majority of cases associated with the Arg 506 Gin point mutation in the factor V gene is present in more than 50 % of patients < 60 years of age with unexplained thrombophilia. The regular APC resistance test is not applicable to plasma from Orally anticoagulated (OAC) or heparinized patients due to decreased levels of vitamin K-dependent clotting factors and to thrombin inhibition by antithrombin, respectively. On admission an extensive coagulation screen yielded the following results (n/normal, t/elevated, I/reduced, +/positive, -/negative): PT t, aPTT t, Tr n, factor II, V, VIII n, factor VII, IX, XI, XII /,, fibrinogan t, ATIII n, protein C, S *, activated protein C sensitivity ratio 1.92 ($), FV-Leidenmutation PCR -, fibrinolytic system n, TAT t, Ft÷2 t, lupus anticoagulant +, heparin induced platelet antibodies +; no diagnosis of a specific autoimmuna disorder could be made. cache = ./cache/cord-006860-a3b8hyyr.txt txt = ./txt/cord-006860-a3b8hyyr.txt === reduce.pl bib === id = cord-023865-6rafp3x3 author = Surjit, Milan title = The Nucleocapsid Protein of the SARS Coronavirus: Structure, Function and Therapeutic Potential date = 2009-07-22 pages = extension = .txt mime = text/plain words = 9210 sentences = 448 flesch = 45 summary = Towards the end of the article, we will also discuss some recent reports regarding the possible clinically relevant use of the nucleocapsid protein, as a candidate diagnostic tool and vaccine against SARS-CoV infection. Interestingly, biochemically mediated inhibition of GSK3 activity in SARS-CoV infected cells also leads to around 80% reduction in viral titer and subsequent induction of a virus-induced cytopathic effect. Further, S-phase specific gene products like cyclin E and CDK2 were found to be downregulated in SARS-CoV infected cell lysate, which suggested that the observed phenomenon may be relevant in vivo. Based on this observation, Palese's laboratory has studied the IFN inhibitory property of different SARS-CoV proteins, which revealed that ORF3, ORF6 as well as the N-protein have the ability to independently inhibit IFN production through different mechanisms. Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells cache = ./cache/cord-023865-6rafp3x3.txt txt = ./txt/cord-023865-6rafp3x3.txt === reduce.pl bib === id = cord-020664-m47ejlsn author = Schlüter, Klaus-Dieter title = Intrakrine, parakrine und autokrine Funktionen des PTH/PTHrP-Systems date = 2006 pages = extension = .txt mime = text/plain words = 7814 sentences = 915 flesch = 53 summary = Ein groûer Unterschied zwischen dem namensgebenden Peptid der Familie, PTH, und den beiden strukturverwandten Proteinen PTHrP und TIP39 ist, dass PTHrP und TIP39 hauptsåchlich auto-, para-oder intrakrin wirken, wohingegen die PTH-Effekte vorwiegend endokriner Natur sind. Demgegençber gibt es aber auch Untersuchungen, die zeigen, dass in der N-terminalen Region von PTH und PTHrP ebenfalls Sequenzen vorhanden sind, die den PLC/PKC-Signal-Weg aktivieren kaennen (Takasu et al. Aufgrund des Vorkommens von biologisch aktiven mittregionalen PTHrP-Fragmenten kann vermutet werden, dass fçr diese Teilpeptide auch entsprechende Rezeptoren existieren, da diese Peptide nicht in der Lage sind, mit dem klassischen PTH1R zu interagieren. Transgene Måuse, die entweder PTHrP oder aber PTH1R in den Glattmuskelzellen der Gefåûe çberexprimieren, sind hypotensiv und weisen eine gestaerte Reaktion bei Applikation von Vasodilatoren auf Qian et al. 1028±1035 a 1.6 Intrakrine, parakrine und autokrine Funktionen des PTH/PTHrP-Systems Nickols GA, Nana AD, Nickols MA, DiPette DJ, Asimakis GK (1989) Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor cache = ./cache/cord-020664-m47ejlsn.txt txt = ./txt/cord-020664-m47ejlsn.txt === reduce.pl bib === id = cord-048344-ps3mnpzq author = Zhu, Xiaowei title = ProCAT: a data analysis approach for protein microarrays date = 2006-11-16 pages = extension = .txt mime = text/plain words = 5728 sentences = 300 flesch = 48 summary = Here we report a new approach, ProCAT, which corrects for background bias and spatial artifacts, identifies significant signals, filters nonspecific spots, and normalizes the resulting signal to protein abundance. In addition, spatial variations can be reduced efficiently through a novel two-parameter signal normalization approach and calling positive spots locally. A scaling method that reduces signal variations among spots of the same proteins at different array locations decreases spatial artifacts. The average values are then used to correct the signal of the central spot to To test the performance of this two-parameter scaling approach for signal normalization within one slide, we designed a test microarray containing multiple positive controls printed at different positions on the slide. Processed data including analysis parameters, a list of positive spots with protein annotations, and normalized signal intensities will be available for the users to download from the server. cache = ./cache/cord-048344-ps3mnpzq.txt txt = ./txt/cord-048344-ps3mnpzq.txt === reduce.pl bib === id = cord-034191-qqb2knmo author = Alayi, Tchilabalo D. title = Tandem Mass Tag-Based Serum Proteome Profiling for Biomarker Discovery in Young Duchenne Muscular Dystrophy Boys date = 2020-10-06 pages = extension = .txt mime = text/plain words = 8942 sentences = 439 flesch = 48 summary = In this study, we sought to optimize and standardize a serum processing workflow in combination with tandem mass tag (TMT) multiplexing strategy to systematically survey the serum proteome of young untreated DMD boys and agematched healthy controls and identify biomarkers associated in the early stages of the disease. Serum samples from 4 year-old glucocorticoid naive DMD patients (n = 9) and age-matched healthy controls (n = 9) were processed for proteome profiling using our standardized multiplexing TMT-based mass spectrometry method described above. As expected, a large number of identified biomarkers (50%) that were found to be elevated in sera of these young DMD boys relative to the healthy controls were of muscle origin based on Gene Ontology molecular function annotations ( Figure S2 ) and information collected using Mass Spectrometry Data Analysis tools. cache = ./cache/cord-034191-qqb2knmo.txt txt = ./txt/cord-034191-qqb2knmo.txt === reduce.pl bib === id = cord-018963-2lia97db author = Xu, Ying title = Protein Structure Prediction by Protein Threading date = 2010-04-29 pages = extension = .txt mime = text/plain words = 15309 sentences = 716 flesch = 48 summary = Their follow-up work (Elofsson et aI., 1996; Fischer and Eisenberg, 1996; Fischer et aI., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et aI., 1992) on protein fold recognition led to the development of a new brand ofpowerful tools for protein structure prediction, which we now term "protein threading." These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many ofthe proteins encoded in the hundreds of genomes that have been sequenced up to now. cache = ./cache/cord-018963-2lia97db.txt txt = ./txt/cord-018963-2lia97db.txt === reduce.pl bib === id = cord-023647-dlqs8ay9 author = nan title = Sequences and topology date = 2003-03-21 pages = extension = .txt mime = text/plain words = 4505 sentences = 747 flesch = 69 summary = Nucleotide Sequence Analysis of the L G~ne of Vesicular Stomafltia Virus (New Jersey Serotype) --Identification of Conserved Domai~L~ in L Proteins of Nonsegmented Negative-Strand RNA Viruses DERSE I~ Equine Infectious Anemia Virus tat--Insights into the Structure, Function, and Evolution of Lentivtrus tran.~Activator Proteins Ho~tu~ ~ s71 is a Ehylngcueticellly Distinct Human Endogenous Reteovtgal 1Rlement with Structural mad Sequence Homology to Simian Sarcoma Virus (SSV). Distinct Fercedoxins from Rhodobacter-Capsulstus -Complete Amino Acid Sequences and Molecular Evolution Complete Amino Acid Sequence and Homologies of Human Erythrocyte Membrane Protein Band 4.2. Identification of Two Highly Conserved Amino Acid Sequences Amon~ the ~x-subunits and Molecular ~ The Predicted Amino Acid Sequence of ct-lnternexin is that of a novel Neuronal lntegmedla~ ~ent Protein Inttaspecific Evolution of a Gene Family Coding for Urinary Proteins Attalysi~ of CDNA for Human ~ AJudgyrin I~dicltes a Repeated Structure with Homology to Tissue-Differentiation a~td Cell-Cycle Control Protein cache = ./cache/cord-023647-dlqs8ay9.txt txt = ./txt/cord-023647-dlqs8ay9.txt === reduce.pl bib === id = cord-021772-5v4gor2v author = Levine, Gwendolyn J. title = Cerebrospinal Fluid and Central Nervous System Cytology date = 2019-05-31 pages = extension = .txt mime = text/plain words = 12646 sentences = 768 flesch = 46 summary = 45, 46 In a recent study of 106 canine CSF samples without pleocytosis (TNCC <5/μL) but containing at least 500 RBCs/μL, the mean percentage of neutrophils (45.2% versus 5.7%), percentage of samples with eosinophils present (36.8% versus 6.8%), and mean protein concentration (40 mg/dL versus 26 mg/dL) were found to be significantly increased in the samples with blood contamination when compared with controls. 4 A study of cats with CNS cryptococcosis showed organisms in 9 of 11 of the CSF samples, and a majority of cases (9 of 10) had neutrophilic pleocytosis and increased protein concentration (8 of 10). A case series of five cats showed CSF ranging from normal to marked neutrophilic pleocytosis with moderately elevated protein concentration and variable correlation to clinical outcome. 85 A study of eight dogs with natural infection (confirmed by CNS tissue-PCR and histopathology) showed lymphocytic pleocytosis in all samples and normal protein concentrations. cache = ./cache/cord-021772-5v4gor2v.txt txt = ./txt/cord-021772-5v4gor2v.txt === reduce.pl bib === id = cord-020788-a33vcapl author = Gottardi, Cara J. title = Signals and Mechanisms of Sorting in Epithelial Polarity date = 2008-05-22 pages = extension = .txt mime = text/plain words = 13900 sentences = 598 flesch = 39 summary = At the electron-microscopic level, one of the most apparent and fundamental features of this cell type is its polarized organization of intracellular organelles and its structurally and compositionally distinct lumenal (apical) and serosal (basolateral) plasma-membrane domains. As noted above, in hepatocytes all apical proteins studied to date make use of this indirect pathway for apical delivery (Bartles et al., 1987) , while cell lines derived from intestine and kidney can employ both routes for surface delivery (Matter et al., 1990; Casanovaet al., 1991; Low et al., 1991) While the details of the routes have been determined for a number of sorting pathways, the molecular signals and recognition components which control each of them are not well understood. The observation that the influenza and vesicular stomatitis viruses bud from opposite surface domains of polarized MDCK cells (Madin Darby Canine Kidney) (Rodriguez-Boulan and Sabatini, 1978) spawned an extensive search in which chimeric and deletion analyses were applied to the problem of identifying the underlying apical and basolateral sorting signals (reviewed in Caplan and Matlin, 1989) . cache = ./cache/cord-020788-a33vcapl.txt txt = ./txt/cord-020788-a33vcapl.txt === reduce.pl bib === id = cord-048471-7jszm1nd author = Salim, Omar title = Functional Analysis of the 5′ Genomic Sequence of a Bovine Norovirus date = 2008-05-14 pages = extension = .txt mime = text/plain words = 5646 sentences = 246 flesch = 49 summary = Although slightly larger than predicted the N-term protein was detected in a processed form in vivo, thus not only demonstrating initial translation of the ORF1 polyprotein but also activity of the viral protease. Previous studies of norovirus polyprotein processing have yielded three major products following in vitro transcription and translation, representing the uncleaved 3ABCD, N-term and 2C proteins. In addition, this important observation also confirms for the first time that the JV 3C protease was active in cells transfected with capped RNA as the size of the V5/N-term indicated successful cleavage of the protein from the ORF1 polyprotein. Unlike similarly studied human noroviruses JV initially did not appear to express the N-terminal protein, presenting the possibility that the encoding RNA sequence had a regulatory function itself, most likely involved in translation initiation in an IRES-like manner. cache = ./cache/cord-048471-7jszm1nd.txt txt = ./txt/cord-048471-7jszm1nd.txt === reduce.pl bib === id = cord-020235-stcrozdw author = nan title = Abstracts of Papers Presented at the 38th Meeting of the Deutsche Gesellschaft für Hygiene und Mikrobiologie, Virology Section, Göttingen, 5.–8.10.1981 date = 2012-03-15 pages = extension = .txt mime = text/plain words = 13494 sentences = 843 flesch = 58 summary = Hepatitis A virus (HAV) was isolated directly from human stool in diploid human fibroplasrs, Viral antigen was expressed only after 210 days of incubation of the infected cultures. Univ., 0-8700 Wiirzburg Effect of Measles (SSPE) Antiserum on Viral Surface Proteins and Hormone Receptor Activity in C6/SSPE Persistently Infected Cells BARRETT, P. Inst, of Genetics, Univ., 0-5000 Co logne Virus-Cell DNA Recombinants in Human Cells Lytically Infected by Ad2 NEUMANN, R., WEYER, U., and DOERFLER, W. In vitro, however, the gag-specific peptide sequences are cleaved off upon addition of the purified viral piS protease; in the case of the replication-defective, transforming avian sarcoma virus PRC II the cleaved nongag part has a ryrosine-phosphorylaring kinase activity similar to that described for the RSV src-gene product pp60 src . f. Virologie, Univ., D·6300 Giefen, 3 A protein of a molecular weight of about 38.000 d has been found to be phosphorylated 1 h after the onset of cell transformation by Rous sarcoma virus (RSV). cache = ./cache/cord-020235-stcrozdw.txt txt = ./txt/cord-020235-stcrozdw.txt === reduce.pl bib === id = cord-023726-2fduzqyb author = STRAUSS, JAMES H. title = The Structure of Viruses date = 2012-07-27 pages = extension = .txt mime = text/plain words = 10614 sentences = 633 flesch = 57 summary = Also shown for each family is the presence or absence of an envelope in the virion, the triangulation number (defined later) if the virus is icosahedral, the morphology of the nucleocapsid or core, and figure numbers where the structures of members of a family are illustrated. Structural studies of viruses have shown that the capsid proteins that form the virions of many plant and animal icosahedral viruses have a common fold. The largest particle is the nucleocapsid of herpes simplex virus, which is 1250 Å in diameter and has T=16 symmetry (the virion is enveloped but only the nucleocapsid is regular FIGURE 2.5 Gallery of three-dimensional reconstructions of icosahedral viruses from cryoelectron micrographs. For most RNA viruses, nucleocapsids can be recognized as distinct structures within the infected cell and can be isolated from virions by treatment with detergents that dissolve the envelope. cache = ./cache/cord-023726-2fduzqyb.txt txt = ./txt/cord-023726-2fduzqyb.txt === reduce.pl bib === id = cord-103528-3tib5o1m author = Ahmed, Asad title = DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity date = 2020-09-28 pages = extension = .txt mime = text/plain words = 3798 sentences = 242 flesch = 54 summary = title: DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity Here, we have incorporated Convolutional Neural Networks that find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies towards a diverse set of ligands. Initial raw data database created contained protein structures in PDB format, protein sequences in FASTA format, ligand in SDF format and binding affinity values of corresponding protein-ligand pairs for 5464 complexes. We propose a deep-learning based approach to predict ligand (eg., drug)-target binding affinity using only structures of target protein (PDB format) and ligand (SDF format) as inputs. We have trained two models to predict the binding affinity between protein and ligand in a given complex. We have constructed a novel dataset that represents a diverse set of ligands and using a novel deep learning based approach we have achieved significant improvement in prediction of binding affinity of protein-ligand complexes. cache = ./cache/cord-103528-3tib5o1m.txt txt = ./txt/cord-103528-3tib5o1m.txt === reduce.pl bib === id = cord-104279-choywmwd author = nan title = Membrane protein sorting in the yeast secretory pathway: evidence that the vacuole may be the default compartment date = 1992-10-01 pages = extension = .txt mime = text/plain words = 9856 sentences = 411 flesch = 52 summary = First, to determine if the lumenal domain was sorted to the vacuole when expressed in the secretory pathway as a soluble protein, a gene fusion was used to create the protein ctFss-B, consisting of the NH2-terminal ER-targeting signal sequence of prepro-t~ factor fused to the lumenal domain of DPAP B at residue 49 ( Fig. 1 B) . To ad-dress the possibility that the mutant constructs analyzed in this study were mislocalized to the plasma membrane followed by rapid endocytic uptake to the vacuole, indirect immunofluorescence experiments were performed on BB-Inv, B-A-B, A20-BB, and/x22-AA-B expressed in a secl strain at 34~ As a positive control for accumulation in secretory vesicles, the localization of the fusion protein Fusl-LacZp was analyzed (Trueheart et al., 1987) . cache = ./cache/cord-104279-choywmwd.txt txt = ./txt/cord-104279-choywmwd.txt === reduce.pl bib === id = cord-026012-r0w0jbpg author = TENNANT, BUD C. title = Gastrointestinal Function date = 2014-06-27 pages = extension = .txt mime = text/plain words = 19858 sentences = 1049 flesch = 50 summary = In the dog, gastric juice is produced in the resting state at a rate of approximately 5 ml/hour (Gray and Bûcher, 1941) , and the composition is similar to that of the basal component, containing practi cally no peptic activity or hydrochloric acid. When the flow of gastric juice is stimulated maximally, the dog may produce 80 ml or more per hour (Gray and Bûcher, 1941) , and this secretion contains large amounts of peptic activity and hydrochloric acid. The endopeptidases and exopep(Table II) , producing free amino acids, which are absorbed directly, or small peptides, which are further hydrolyzed by the aminopeptidases of the intestinal mucosa (see Section III,C). Despite the long interest in and controversy regarding the subject of this section, the relative amounts of the various types of protein digestion products, i.e., peptides and amino acids, which are actually absorbed by intestinal mucosal cells during normal digestion are still not known. cache = ./cache/cord-026012-r0w0jbpg.txt txt = ./txt/cord-026012-r0w0jbpg.txt === reduce.pl bib === id = cord-022499-7d58f1k3 author = Mall, Sanjay title = Transmembrane α helices date = 2004-01-07 pages = extension = .txt mime = text/plain words = 12212 sentences = 583 flesch = 55 summary = For example, if effects were averaged over three shells of lipids, changes in fatty acyl chain lengths by 4 and 10 carbons from that giving optimal interaction would decrease lipid-protein binding constants by factors of 1.6 and 21, respectively. These results suggest that the effects of charge on the interactions between phospholipids and transmembrane ot helices will often be rather small and will be strongly dependent on the detailed structure of the peptide and its orientation in the membrane. However, there is evidence for the presence of a small number of "special" anionic phospholipids binding to some membrane proteins, acting as "cofactors." An example is provided by cytochrome c oxidase, whose crystal structure shows the presence of a lipid molecule bound between the transmembrane a helices (Iwata et al., 1995) . It could therefore be that matching of the thickness of the lipid bilayer and the transmembrane length of the protein is important in retention in ER, as was suggested for the Golgi complex. cache = ./cache/cord-022499-7d58f1k3.txt txt = ./txt/cord-022499-7d58f1k3.txt === reduce.pl bib === id = cord-022779-himray6q author = nan title = Abstracts of oral presentations date = 2005-06-10 pages = extension = .txt mime = text/plain words = 3621 sentences = 164 flesch = 41 summary = Here we present a novel strategy to synthesize proteins through a chemical ligation using unprotected peptide segments. Using short portions (7-11 amino acid) rich in positively charged residues from either human lactoferricin or the MARCKS protein as templates, a panel of 70 peptides each possessing a specific chemical structure was synthesized. Subsequent functionalization of such azide groups via Staudinger or "Click" chemistry should provide a convenient method for linking proteins with a diverse array of probes, biomolecules, surfaces and other materials under mild conditions. Moreover, the advantages of peptide and protein chemical synthesis over recombinant-DNA methods are increasingly being used to provide rapid structure-activity information of complex bioactive peptides, small proteins and functional receptor domains. Thus, these new peptides bear all of the requirements which are necessary for formation of cooperatively interacting helical structures and, furthermore, contain domains for cooperative sheet aggregation as well. cache = ./cache/cord-022779-himray6q.txt txt = ./txt/cord-022779-himray6q.txt === reduce.pl bib === id = cord-136540-2h2braww author = Buehler, Markus J. title = Liquified protein vibrations, classification and cross-paradigm de novo image generation using deep neural networks date = 2020-04-16 pages = extension = .txt mime = text/plain words = 3684 sentences = 209 flesch = 51 summary = Here we present a method to transform these molecular vibrations into materialized vibrations of thin water films using acoustic actuators, leading to complex patterns of surface waves, and using the resulting macroscopic images in further processing using deep convolutional neural networks. Specifically, the patterns of water surface waves for each protein structure is used to build training sets for neural networks, aimed to classify and further process the patterns. Once trained, the neural network model is capable of discerning different proteins solely by analyzing the macroscopic surface wave patterns in the water film. This article focuses on a different perspective and reports a distinct, complementary and translational approach, in which we transform these molecular vibrations into vibrations of thin water films using acoustic actuators, leading to visual images of complex materialized patterns of surface waves. We use DeepDream [39] to generate novel images by activating select layers in the deep neural network, based on the model trained against the water surface images. cache = ./cache/cord-136540-2h2braww.txt txt = ./txt/cord-136540-2h2braww.txt === reduce.pl bib === id = cord-034823-ogwjzfgf author = Guo, Hao-Bo title = A Suggestion of Converting Protein Intrinsic Disorder to Structural Entropy Using Shannon’s Information Theory date = 2019-06-14 pages = extension = .txt mime = text/plain words = 7021 sentences = 377 flesch = 55 summary = We propose a framework to convert the protein intrinsic disorder content to structural entropy (H) using Shannon's information theory (IT). Hence, it is useful to know the relationships between the intrinsic structural entropies and the information that can be derived (Equation (3)) from the residual disorder contents, which, in turn, can be predicted based on the protein amino acid sequences. In the CR-space, Ci sets the upper limit and Ri gives the intrinsic ratio between the two quantities of the total Hi and Ii of the i-th protein Pi. Based on the Gaussian distribution in both log2C and log2R, the protein distributions in the CR-space are represented in Figure 2 , for proteins expressed in representative prokaryotes (bacteria and archaea, Figure 2A ), eukaryotes ( Figure 2B ), viruses ( Figure 2C ), and datasets collected from the DisProt database [25] and protein data bank (PDB) [26] ( Figure 2D ). cache = ./cache/cord-034823-ogwjzfgf.txt txt = ./txt/cord-034823-ogwjzfgf.txt === reduce.pl bib === id = cord-023208-w99gc5nx author = nan title = Poster Presentation Abstracts date = 2006-09-01 pages = extension = .txt mime = text/plain words = 70854 sentences = 3492 flesch = 43 summary = In order to develop a synthetic protocol by an automated instrumentation, increasing yield, purity of the crude, and reaction time, a microwave-assisted solid phase peptide synthesis was validated comparing the use of the new generation of Triazine-Based Coupling Reagents (TBCRs) with a series of commonly used ones. Ubiquitinium is a well known mechanism in protein degredation of Eukaryotic cells ,in which many obsolte and corrupted three dimentional structure protein ,become marked by covalent attachment of ubuquitin through a multi-step enzymatic pathway.Ubiquitin is a small ,8.5 kDa peptide of 76 amino acid residues that targets such substrtes for proteolysis in proteasome .Recnt studies showed that an extra cellular ubiquitination process also taking place in the epididymes of humans and other animals marks protein on the surface of the defective sperm .it appears that structurally and functionally defective sperm become surface ubiquitinated by epididymal epithelial cells. This head-to-tailcyclized 14-amino-acid peptide contains one disulfide bridge and a lysine residue (Lys5) present in the P1 position, which is responsible for inhibitor specificity.As was reported by us and other groups, SFTI-1 analogues with one cycle only retain trypsin inhibitory activity. cache = ./cache/cord-023208-w99gc5nx.txt txt = ./txt/cord-023208-w99gc5nx.txt === reduce.pl bib === id = cord-024989-0o6agnrc author = Li, Qihao title = Prediction and analysis of key protein structures of 2019-nCoV date = 2020-05-12 pages = extension = .txt mime = text/plain words = 3244 sentences = 172 flesch = 58 summary = Aim: The purpose of this study was to predict and analyze the structure and function of 2019-novel Coronavirus (nCoV) key proteins. Differential key protein structure analysis of 2019-nCoV Although some amino acids were inserted in two positions of nsp3 in orf1ab [23] , the insertion sites were in the nsp3b and nsp3c regions, which are mainly related to the binding reaction of nucleic acids. Back-mutating mutant amino acids to study the functional change of RBD of S protein In order to study the effect of interactional amino acid changes in 2019-nCoV-ACE2 binding region RBD, we mutated the changed three amino acid residues (Glu 470 , Gln 484 and Asn 487 ) within the RBD structure back to the original amino acids. • We elaborated the sequence and structure differences in each key protein of 2019-nCoV and other bat SARS coronaviruses (CoVs). cache = ./cache/cord-024989-0o6agnrc.txt txt = ./txt/cord-024989-0o6agnrc.txt === reduce.pl bib === id = cord-023770-ymxapsv6 author = nan title = Closteroviridae date = 2011-11-23 pages = extension = .txt mime = text/plain words = 3662 sentences = 197 flesch = 53 summary = In general, capsid proteins and their homologs (CPm) show a significant degree of sequence conservation and the duplicate copies probably retain the general spatial folding and some crucial properties of the CPs. Notable exception are a group of ampeloviruses with the smallest genomes in the family [e.g. grapevine leafrollassociated virus 4 (GLRaV-4), GLRaV-5, GLRaV-6, GLRaV-9, pineapple mealybug wilt-associated virus 1(PMWaV-1) and PMWaV-3] which do not appear to possess CPm. The genome expression strategy is based on: (i) proteolytic processing of the polyprotein encoded by ORF1a; (ii) 1 Pos. ssRNA ribosomal frameshift for the expression of the RdRp domain encoded by ORF1b, a mechanism not found in other ()RNA plant viruses; (iii) expression of the downstream ORFs via the formation of a nested set of 3 co-terminal sub-genomic RNAs (sgRNAs). cache = ./cache/cord-023770-ymxapsv6.txt txt = ./txt/cord-023770-ymxapsv6.txt === reduce.pl bib === id = cord-022235-6ircruag author = Pugsley, Anthony P. title = Later stages in the eukaryotic secretory pathway date = 2012-12-02 pages = extension = .txt mime = text/plain words = 15217 sentences = 667 flesch = 52 summary = Microinjected antibodies recognizing the C-terminal, cytoplasmic tails of plasma membrane proteins can prevent their trans port to the cell surface (25, 590) , but this is probably due to antibodyinduced changes in protein conformation which make the protein incom petent for transport along the secretory pathway, rather than to inhibition of receptor-secretory protein interactions. (545) found that pro-a-factor processing was blocked by sec mutations, which prevented protein movement through the Golgi, and that mature α factor was normally present in secretory vesicles en route to the cell surface. The TGN is the most acidic Golgi compartment, although the pH is almost certainly not as low as in secretory granules (823) or in lysosomal sorting vesicles, in which low pH causes the dissociation of lysosomal proteins from the mannose-6-phosphate receptor (577) (see Section V.G.5). (1022) also observed the transient accumulation of one of these enzymes in coated vesicles, which, they proposed, are specifically involved in the sorting of lysosomal proteins from the secretory pathway. cache = ./cache/cord-022235-6ircruag.txt txt = ./txt/cord-022235-6ircruag.txt === reduce.pl bib === id = cord-017999-saxwqc2j author = Travers, Andrew A. title = Gene Regulation by HMGA and HMGB Chromosomal Proteins and Related Architectural DNA-Binding Proteins date = 2005 pages = extension = .txt mime = text/plain words = 6332 sentences = 294 flesch = 48 summary = The eukaryotic abundant high mobility group HMGA and HMGB proteins can act as architectural transcription factors by promoting the assembly of higher-order protein-DNA complexes which can either activate or repress gene expression. Similarly rat SSRPl has been shown to facilitate the DNA binding of serum response factor and human SSRPl is associated with the y isoform of p63 in vivo at the endogenous MDM22inAp2nfl'"^^ promoters.^^ In most of these cases, the interaction of the HMG protein with the transcription factor has been detected in vitro and could, in principle, serve as the mechanism for recruitment of HMGB 1 or 2 to particular DNA sites. cache = ./cache/cord-017999-saxwqc2j.txt txt = ./txt/cord-017999-saxwqc2j.txt === reduce.pl bib === id = cord-021393-9loesliv author = Meade, H.M. title = EXPRESSION OF RECOMBINANT PROTEINS IN THE MILK OF TRANSGENIC ANIMALS date = 2007-09-02 pages = extension = .txt mime = text/plain words = 8080 sentences = 416 flesch = 48 summary = To date (1997) , probably more than 50 proteins have been expressed in the milk of transgenic mice, rats, rabbits, goats, sheep, pigs, and dairy cows. Transgenes containing sequences of several milk protein genes, reviewed by Maga and Murray (1995) and Echelard (1996) , have been used to direct the expression of exogenous proteins to the lactating mammary gland. Regulatory sequences from several milk-specific genes have been isolated and tested in transgenic animals: ovine ~-lactoglobulin; murine, rat, and rabbit whey acidic protein (WAP); bovine ~-sl casein; rat, rabbit, and goat f~-casein; and guinea pig, ovine, caprine, and bovine ~-lactalbumin. A 17.2 kbp region located upstream of the rabbit WAP gene directs high level expression of a functional human protein variant in transgenic mouse milk High level production of human growth hormone in the milk of transgenic mice: The upstream region of the whey acidic protein (WAP) gene targets transgene expression to the mammary gland cache = ./cache/cord-021393-9loesliv.txt txt = ./txt/cord-021393-9loesliv.txt === reduce.pl bib === id = cord-103320-2rpr7aph author = Bhandari, Bikash K. title = Solubility-Weighted Index: fast and accurate prediction of protein solubility date = 2020-03-26 pages = extension = .txt mime = text/plain words = 4889 sentences = 333 flesch = 50 summary = Results We have discovered that global structural flexibility, which can be modeled by normalised B-factors, accurately predicts the solubility of 12,216 recombinant proteins expressed in Escherichia coli. Protein solubility, at least in part, depends upon extrinsic factors such as ionic strength, temperature and pH, as well as intrinsic factors-the physicochemical properties of the protein sequence and structure, including molecular weight, amino acid composition, hydrophobicity, aromaticity, isoelectric point, structural propensities and the polarity of surface residues (Wilkinson and Harrison 1991; Chiti et al. 2003 ) Among these sets of B-factors, sequence composition scoring using the most recently published set of normalised B-factors produced the highest AUC score ( To improve the prediction accuracy of solubility, we iteratively refined the weights of amino acid residues using the Nelder-Mead optimisation algorithm (Nelder and Mead 1965) . To understand the properties of soluble and insoluble proteins, we determined the enrichment of amino acid residues in the PSI:Biology targets relative to the eSOL sequences (see Methods). cache = ./cache/cord-103320-2rpr7aph.txt txt = ./txt/cord-103320-2rpr7aph.txt === reduce.pl bib === id = cord-022262-ck2lhojz author = Gromeier, Matthias title = Genetics, Pathogenesis and Evolution of Picornaviruses date = 2007-09-02 pages = extension = .txt mime = text/plain words = 28035 sentences = 1423 flesch = 46 summary = The following viruses have been recognized as picornaviruses on the basis of their genome sequences and physico-chemical properties as well as the result of comparative sequence analyses (see the section on Evolution): equine rhinovirus types I and 2, Aichi virus, porcine enterovirus, avian encephalomyelitis virus, infectious flacherie virus of silkworm Clusters of enteroviruses refer to groups of enteroviruses arranged predominantly according to genotypic kinship (Hyypia et al., 1997) . Briefly, when expression vectors ( Figure 12 .6E) consisting of a gag gene (encoding p17-p24; 1161 nt) of human immunodeficiency virus that was fused to the N-terminus of the poliovirus polyprotein (Andino et al., 1994; Mueller and Wimmer, 1998) were analysed after transfection into HeLa cells, the genomes were not only found to be severely impaired in viral replication but they were also genetically unstable (Mueller and Wimmer, 1997) . cache = ./cache/cord-022262-ck2lhojz.txt txt = ./txt/cord-022262-ck2lhojz.txt === reduce.pl bib === id = cord-252147-bvtchcbt author = Domingo-Espín, Joan title = Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles date = 2011-11-15 pages = extension = .txt mime = text/plain words = 17193 sentences = 888 flesch = 39 summary = Modular protein engineering, virus-like particles (VLPs), and other self-assembling entities are envisioned as modulatable novel protein nanoparticles able to include many desirable properties in the correct delivery of drugs and nucleic acids. 120 Modular fusion proteins that combine distinct functions required for cell type-specific uptake and intracellular delivery of DNA or drugs present an attractive approach for the development of self-assembling vectors for targeted gene or drug delivery. 215, 216 Although VLP-based vaccines have been primarily developed for their use against the corresponding virus, in the last decades genetic engineering or chemical modifications have been applied in order to generate chimeric VLPs. Thus, on the one hand, commonly short heterologous peptide epitopes or full proteins that are unable to form VLPs or that are unsafe for vaccination have been presented on surface-exposed loops or fused to N-or C-exposed termini of structural viral capsid proteins on VLPs. 154, 161, 210 Different HPV, 217-219 HBV, 220,221 parvovirus, 222, 223 and chimeric polyoma VLPs have been engineered 170, 175 and tested for different applications including vaccination against viral or bacterial diseases, against virus-induced tumors, and more recently, for immunotherapy of nonviral cancer. cache = ./cache/cord-252147-bvtchcbt.txt txt = ./txt/cord-252147-bvtchcbt.txt === reduce.pl bib === id = cord-031937-qhlatg84 author = Verma, Anukriti title = Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach date = 2020-09-15 pages = extension = .txt mime = text/plain words = 6760 sentences = 326 flesch = 31 summary = In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. The contributions of the microorganisms in the co-evolved IBD and ReA as part of the disease network was created through the interactive maps of the essential host interaction proteins (verified using literature survey) and the information processed through gene expression data analysis 64 . The pathways of the above host interacting proteins were found out using KEGG database that provides ontologies for proteins related to biological processes 67 www.nature.com/scientificreports/ Subsequently, the role of drugs or inhibitors used to suppress the effect of IBD and ReA such as indomethacin, prednisone, ciprofloxacin, sulfasalazine, azathioprine, methotrexate and hydroxychloroquine was scored in the disease network through their docking studies against the potential targets (both host as well microbial targets) as per published methodologies 68, 69 . cache = ./cache/cord-031937-qhlatg84.txt txt = ./txt/cord-031937-qhlatg84.txt === reduce.pl bib === id = cord-222664-4qyrtzhu author = Coban, Mathew title = Attacking COVID-19 Progression using Multi-Drug Therapy for Synergetic Target Engagement date = 2020-07-06 pages = extension = .txt mime = text/plain words = 11220 sentences = 638 flesch = 46 summary = We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors; S/Ace2, Tmprss2, Cathepsins L and K, and Mpro to prevent binding, membrane fusion and replication of the virus, respectively. Using a computational pipeline that aimed to expeditiously identify lead compounds against COVID-19, we combined compound library preparation, molecular modeling, and structure simulations to generate an ensemble of conformations and increase high quality docking outcomes against two essential SARS-CoV-2 viral proteins and their host protein interactions; S/Ace2, Tmprss2, Cathepsin L and K, and M pro that are known to control both viral binding, entry and virus replication (Fig. 1A) . cache = ./cache/cord-222664-4qyrtzhu.txt txt = ./txt/cord-222664-4qyrtzhu.txt === reduce.pl bib === id = cord-243806-26n22jbx author = Vandelli, Andrea title = Structural analysis of SARS-CoV-2 and prediction of the human interactome date = 2020-03-30 pages = extension = .txt mime = text/plain words = 5252 sentences = 317 flesch = 52 summary = Here, we performed sequence and structural alignments among 62 SARS-CoV-2 strains and identified the conservation of specific elements in the spike S region, which provides clues on the evolution of domains involved in the binding to ACE2 and sialic acid. As highly structured regions of RNA molecules have strong propensity to form stable contacts with proteins 14 and promote assembly of specific complexes 15, 16 , SARS-CoV-2 domains enriched in double-stranded content are expected to establish interactions within host cells that are important to replicate the virus 17 . Analysis of functional annotations carried out with GeneMania 46 revealed that proteins interacting with the 5' of SARS-CoV-2 RNA are associated with regulatory pathways involving NOTCH2, MYC and MAX that have been previously connected to viral infection processes ( Fig. 4E) 47, 48 . cache = ./cache/cord-243806-26n22jbx.txt txt = ./txt/cord-243806-26n22jbx.txt === reduce.pl bib === id = cord-196265-mvnkkcow author = M'esz'aros, B'alint title = Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications date = 2020-04-21 pages = extension = .txt mime = text/plain words = 12653 sentences = 666 flesch = 47 summary = We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif resource, ELM, and were presented with candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton and cell signalling. Proximity-based mass spectrometry on the MHV replication complex further revealed that the RTC environment repurposes components from the host autophagy, vesicular trafficking and translation machineries (V'kovski et al., 2019) In the present work, we identify a set of conserved SLiM candidates in the ACE2 and integrin proteins, which are likely to act in the cell entry system of SARS-CoV-2. The C-terminal tail of both subunits share a high degree of sequence similarity, and similarly to ACE2, contain several known and candidate SLiMs (see Table 1 and Figure 6 ) that propagate signals in the cytoplasm and regulate integrin activity not just through intracellular pathways, but also changing the structural state of the ectodomains determining ligand binding capacity (Anthis and Campbell, 2011) . cache = ./cache/cord-196265-mvnkkcow.txt txt = ./txt/cord-196265-mvnkkcow.txt === reduce.pl bib === id = cord-252304-lwiulri7 author = Fragnoud, Romain title = Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue date = 2015-11-14 pages = extension = .txt mime = text/plain words = 8324 sentences = 433 flesch = 46 summary = ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. CONCLUSION: A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. Fig. 2 Ingenuity Pathway Analysis for host proteins identified in the viral-enriched plasma fraction of patients with dengue. To validate the mass spectrometry data, the levels of selected host proteins were assessed by quantitative ELISA both in the virus-enriched fraction and in individual plasma samples from DF or SD patients. In this regard, further studies are required to assess the prognostic value of host proteins associated with inflammation, complement cascade and coagulation for disease severity by analysis of additional biological samples from patients infected with DV. cache = ./cache/cord-252304-lwiulri7.txt txt = ./txt/cord-252304-lwiulri7.txt === reduce.pl bib === id = cord-022955-vy0qgtll author = nan title = Proteases date = 2005-06-20 pages = extension = .txt mime = text/plain words = 36388 sentences = 1759 flesch = 43 summary = In order to understand the molecular basis of the enzyme-substrate binding mechanism, we employ the synthetic peptide and mass spectrometry-based approaches to investigate the significance of selected amino acid residues that are flanking both sides of the SARS-CoV 3CL pro cleavage site. To contribute to the assignment of a physiological role to genomic-derived peptidases and to make them more accessible for the drug discovery process, we have undertaken a program consisting of mRNA expression profiling, full-length recombinant expression in insect cells, purification and determination of the catalytic activity for the human proteolytic enzymes. This comprehensive analysis of the local backbone properties of SGTI in the free and in the complex form made possible to identify conformational similarities and differences responsible for its efficient binding to the enzyme, and provides a good basis for further studying the structural aspects of protease inhibitor specificity. cache = ./cache/cord-022955-vy0qgtll.txt txt = ./txt/cord-022955-vy0qgtll.txt === reduce.pl bib === id = cord-024193-khdvj6t5 author = Zhang, Hong title = Peptide Arrays date = 2012-01-17 pages = extension = .txt mime = text/plain words = 11358 sentences = 486 flesch = 41 summary = Despite the concern over the potential loss of structural information as a result of the use of peptides as opposed to proteins as molecular probes, peptide arrays have been implemented in a broad range of applications including antibody screening and epitope mapping, characterization of molecular interactions, and enzymatic activity profiling, and they have become a valuable tool for proteomics research. Similarly to DNA/oligonucleotide microarrays, arrays for proteomics studies feature a wide range of molecules including recombinant proteins, complex protein samples, antibodies, peptides, or small molecules that are assembled in an addressable fashion on planar surfaces to allow parallel interrogations for activity and interactions associated with biomolecules at the protein level. cache = ./cache/cord-024193-khdvj6t5.txt txt = ./txt/cord-024193-khdvj6t5.txt === reduce.pl bib === id = cord-023225-5quigar4 author = nan title = Posters date = 2012-08-21 pages = extension = .txt mime = text/plain words = 70251 sentences = 3367 flesch = 43 summary = To further explore the structure-function relationship, a viable synthesis strategy for pseudodesmin A analogues was developed, based on side-chain attachment of the first amino acid to the solid support, followed by stepwise Fmoc solid-phase synthesis of the linear peptide precursor and on-resin head-to-tail cyclization. The cases when the amino acid sequence of a fragment coincided with part of the primary structure of a natural oligopeptide were recorded in the Total protein chemical synthesis requires a case by case design and optimization which is governed by factors such as the solubility of the individual peptide segments, their primary sequence and in particular the presence of "difficult" amino acid residues at ligation junctions such as proline or the location of cysteines. In this study we present synthesis of two series of peptide libraries, which were designed by substitution of Leu in the P5, P6 position of our control peptide (Ac-LLLLRVKR-AMBA) with each of nineteen amino acid residues in order to verifying its influence on activity and selectivity of the resulting analogues. cache = ./cache/cord-023225-5quigar4.txt txt = ./txt/cord-023225-5quigar4.txt === reduce.pl bib === id = cord-103430-x6zzuu7v author = Contu, Lara title = Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay date = 2020-10-12 pages = extension = .txt mime = text/plain words = 8272 sentences = 461 flesch = 56 summary = Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus' hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. Gene ontology (GO) enrichment analyses of protein complexes that could 10 form between the identified host interactors revealed highly significant GO terms related to 11 translation and Nonsense-mediated mRNA Decay (NMD). In addition to ribosomal proteins, many other RNA binding proteins were also 37 identified as having a potential role in SFV replication (Figure 3a (nsP1, nsP2, nsP3-Z, nsP4, capsid and Env) as well as for the merged list (All baits) was also applied. cache = ./cache/cord-103430-x6zzuu7v.txt txt = ./txt/cord-103430-x6zzuu7v.txt === reduce.pl bib === id = cord-033010-o5kiadfm author = Durojaye, Olanrewaju Ayodeji title = Potential therapeutic target identification in the novel 2019 coronavirus: insight from homology modeling and blind docking study date = 2020-10-02 pages = extension = .txt mime = text/plain words = 8125 sentences = 375 flesch = 53 summary = RESULTS: This study describes the detailed computational process by which the 2019-nCoV main proteinase coding sequence was mapped out from the viral full genome, translated and the resultant amino acid sequence used in modeling the protein 3D structure. Our current study took advantage of the availability of the SARS CoV main proteinase amino acid sequence to map out the nucleotide coding region for the same protein in the 2019-nCoV. The predicted secondary structure composition shows a high degree of alpha helix and beta sheets, respectively, occupying 45 and 47% of the total residues with the percentage loop occupancy at 8% regarded as comparative modeling, constructs atomic models based on known structures or structures that have been determined experimentally and likewise share more than 40% sequence homology. cache = ./cache/cord-033010-o5kiadfm.txt txt = ./txt/cord-033010-o5kiadfm.txt === reduce.pl bib === id = cord-253987-83h861lp author = Tada, Takuya title = A soluble ACE2 microbody protein fused to a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2 infection in cell culture date = 2020-09-17 pages = extension = .txt mime = text/plain words = 6830 sentences = 349 flesch = 50 summary = The disulfide-bonded ACE2 microbody protein inhibited entry of lentiviral SARS-CoV-2 spike protein pseudotyped virus and live SARS-CoV-2 with a potency 10-fold higher than unmodified soluble ACE2 and was active after initial virus binding to the cell. In SARS-CoV-2 entry, the virus attaches to the target cell through the interaction of the spike glycoprotein (S) with its receptor, the angiotensin-converting enzyme 2 (ACE2) (Li, 2015; Li et al., 2005; Li et al., 2003) , a plasma membrane protein carboxypeptidase that degrades angiotensin II to angiotensin-(1-7) [Ang-(1-7)] a vasodilator that promotes sodium transport in the regulation of cardiac function and blood pressure (Kuba et al., 2010; Riordan, 2003; Tikellis and Thomas, 2012) . To determine the relative antiviral activity of soluble ACE2 and the ACE2 microbody proteins, we tested their ability to block the infection SARS-CoV-2 Δ19 S protein pseudotyped GFP/luciferase reporter virus. cache = ./cache/cord-253987-83h861lp.txt txt = ./txt/cord-253987-83h861lp.txt === reduce.pl bib === id = cord-023143-fcno330z author = nan title = Molecular aspects of viral immunity date = 2004-02-19 pages = extension = .txt mime = text/plain words = 43425 sentences = 2056 flesch = 47 summary = Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells. cache = ./cache/cord-023143-fcno330z.txt txt = ./txt/cord-023143-fcno330z.txt === reduce.pl bib === id = cord-029957-q7v5gli8 author = Prabhu, D. title = In silico Functional Annotation and Characterization of Hypothetical Proteins from Serratia marcescens FGI94 date = 2020-07-31 pages = extension = .txt mime = text/plain words = 5796 sentences = 311 flesch = 42 summary = Two proteins AGB81206.1 and AGB83112.1 were predicted as a member of the exonuclease-endonuclease-phosphate domain super family which plays a crucial role in the intracellular signaling activities in bacteria (Dlakic, 2000) . The observed function of the HPs helps to understand the crucial role of new proteins in bacterial growth and can be targeted as a potential targets for drug discovery. The protein AGB80728.1 was predicted as Translocation and Assembly Module (TAM), which plays a major role in outer membrane biogenesis and virulence mechanisms in bacterial kingdom (Josts et al., 2017) . This kind of proteins are found in wide variety of prokaryotic and eukaryotic organisms and plays an vital role in cell processes and associated with virulence mechanisms of bacterial pathogens (Cerveny et al., 2013) . Various types of enzymes, transporters, cell division, binding proteins were characterized which play an essential role in the growth, survival virulence and pathogenesis of S. cache = ./cache/cord-029957-q7v5gli8.txt txt = ./txt/cord-029957-q7v5gli8.txt === reduce.pl bib === id = cord-254100-u6x5zd4i author = Taliansky, M.E. title = Involvement of the Plant Nucleolus in Virus and Viroid Infections: Parallels with Animal Pathosystems date = 2010-10-15 pages = extension = .txt mime = text/plain words = 13988 sentences = 662 flesch = 40 summary = An increasing number of reports reveal that similar to the proteins of animal viruses, many plant virus proteins localize in the nucleolus to divert host nucleolar proteins from their natural functions in order to exert novel role(s) in the virus infection cycle. An increasing number of reports reveal that similar to the proteins of animal viruses, many plant virus proteins localize in the nucleolus to divert host nucleolar proteins from their natural functions in order to exert novel role(s) in the virus infection cycle. As their name suggests, MPs are involved in virus spread in infected plants, and the potential role of fibrillarin in this process will be discussed in Section IV.B. The multifunctional PVA (potato virus A)-encoded viral genomelinked protein (VPg) is also able to interact with fibrillarin (Rajamäki and Bonfiglioli et al. cache = ./cache/cord-254100-u6x5zd4i.txt txt = ./txt/cord-254100-u6x5zd4i.txt === reduce.pl bib === id = cord-008777-i2reanan author = nan title = ECB12: 12th European Congess on Biotechnology date = 2005-07-19 pages = extension = .txt mime = text/plain words = 151383 sentences = 7577 flesch = 43 summary = Mollerup Department of Chemical Engineering, Building 229, DTU, 2800 Lyngby, Denmark A variety of factors that govern the properties of proteins are utilized in the development of chromatographic processes for the recovery of biological products including the binding and release of protons, the non-covalent association with non-polar groups (often hydrophobic interactions), the association of small ions (ion exchange) and the highly specific antigen-antibody interaction (affinity interactions). Such fermenters will be needed in order to meet the increasing pressure on costs for low price commodity type products such as single cell protein or food and technical grade enzymes, and to meet the demands of the new wave of white biotech, in which bio-produced chemicals must be made at prices competitive with those of the traditional chemical industry. The presentation will focus on use of the sensitive sandwich hybridization technology for the quantitative analysis of process relevant marker genes in different kind of microbial cell cultures with a focus on the production of recombinant proteins. cache = ./cache/cord-008777-i2reanan.txt txt = ./txt/cord-008777-i2reanan.txt === reduce.pl bib === id = cord-171099-d0qr84xg author = Buehler, Markus J. title = Nanomechanical sonification of the 2019-nCoV coronavirus spike protein through a materiomusical approach date = 2020-03-30 pages = extension = .txt mime = text/plain words = 4509 sentences = 205 flesch = 46 summary = Presenting musical encoding in two versions one in the amino-acid scale and one based on equal temperament tuning the method allows for expressing protein structures in audible space, offering novel avenues to represent, analyze and design architectural features across lengthand time-scales. We further report a hierarchical frequency spectrum analysis of five distinct protein structures, which offer insights into how genetic mutations, and the binding of the virus spike protein to the human ACE2 cell receptor directly influence the audio. What you hear is a multi-layered algorithmic composition featuring both the vibrational spectrum of the entire protein (expressed in sound and rhythmic elements), the sequence and folding of amino acids that compose the virus spike structure, as well as interwoven melodiesforming counterpoint music -reflecting the complex hierarchical intersecting geometry of the protein. cache = ./cache/cord-171099-d0qr84xg.txt txt = ./txt/cord-171099-d0qr84xg.txt === reduce.pl bib === id = cord-029747-8f463wz0 author = Viedma-Poyatos, Álvaro title = Type III intermediate filaments as targets and effectors of electrophiles and oxidants date = 2020-07-17 pages = extension = .txt mime = text/plain words = 12680 sentences = 612 flesch = 34 summary = The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modifications by oxidants and electrophiles, for which their conserved cysteine residue emerges as a hot spot. Appearance of carbonyl groups on proteins can occur by several mechanisms, including oxidation of amino acid lateral chains, oxidative deamination or formation of certain adducts with compounds that retain a free carbonyl group, as in some types of lipoxidation, like Michael addition of cyPG or of HNE, or after glycation or glycoxidation. Early studies using cytoskeleton preparations from several cell types subjected to oxidative in vitro crosslinking with Cu 2+ -phenanthroline showed the formation of homo-and heterodimers of either vimentin and desmin or vimentin and GFAP, which led to propose that both proteins were present in hybrid filaments [85, 86] . cache = ./cache/cord-029747-8f463wz0.txt txt = ./txt/cord-029747-8f463wz0.txt === reduce.pl bib === id = cord-034406-i1hbx3pz author = Matthews, Abigail A. title = Developing inhaled protein therapeutics for lung diseases date = 2020-10-30 pages = extension = .txt mime = text/plain words = 8739 sentences = 395 flesch = 40 summary = Biologic therapeutics such as protein/polypeptide drugs are conventionally administered systemically via intravenous injection for the treatment of diseases including lung diseases, although this approach leads to low target site accumulation and the potential risk for systemic side effects. In comparison, topical delivery of protein drugs to the lung via inhalation is deemed to be a more effective approach for lung diseases, as proteins would directly reach the target in the lung while exhibiting poor diffusion into the systemic circulation, leading to higher lung drug retention and efficacy while minimising toxicity to other organs. This means that high concentrations of the protein drug can be attained in the lung via pulmonary delivery, suggesting that lower doses of inhaled protein can have an equivalent or even superior therapeutic effect for lung diseases when compared to the higher doses that would be needed from systemic administration [9] . cache = ./cache/cord-034406-i1hbx3pz.txt txt = ./txt/cord-034406-i1hbx3pz.txt === reduce.pl bib === id = cord-023209-un2ysc2v author = nan title = Poster Presentations date = 2008-10-07 pages = extension = .txt mime = text/plain words = 111878 sentences = 5398 flesch = 45 summary = Site-specifi c PEGylation of human IgG1-Fab using a rationally designed trypsin variant In the present contribution we report on a novel, highly selective biocatalytic method enabling C-terminal modifi cations of proteins with artifi cial functionalities under native state conditions. Recently, our group report a novel approach to a totally synthetic vaccine which consists of FMDV (Foot and Mouth Disease Virus) VP1 peptides, prepared by covalent conjugation of peptide biomolecules with membrane active carbochain polyelectrolytes In the present study, peptide epitops of VP1 protein both 135-161(P1) amino acid residues (Ser-Lys-Tyr-Ser-Thr-Thr-Gly-Glu-Arg-Thr-Arg-Thr-Arg-Gly-Asp-Leu-Gly-Ala-Leu-Ala-Ala-Arg-Val-Ala-Thr-Gln-Leu-Pro-Ala) and triptophan (Trp) containing on the N terminus 135-161 amino acid residues (Trp-135-161) (P2) were synthesized by using the microwave assisted solid-phase methods. Using as a template a peptide, already identifi ed, with agonist activity against PTPRJ(H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), here we report a structure-activity study carried out through endocyclic modifi cations (Ala-scan, D-substitutions, single residue deletions, substitutions of the disulfi de bridge) and the preliminary biological results of this set of compounds. cache = ./cache/cord-023209-un2ysc2v.txt txt = ./txt/cord-023209-un2ysc2v.txt === reduce.pl bib === id = cord-006229-7yoilsho author = nan title = Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date = 2016-02-06 pages = extension = .txt mime = text/plain words = 133493 sentences = 6804 flesch = 42 summary = It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1). cache = ./cache/cord-006229-7yoilsho.txt txt = ./txt/cord-006229-7yoilsho.txt === reduce.pl bib === id = cord-048360-n9sih438 author = Villard, Viviane title = Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif date = 2007-07-25 pages = extension = .txt mime = text/plain words = 4794 sentences = 228 flesch = 45 summary = To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. Here, we focus on the Pf parasite erythrocytic stage, a target of protective antibodies and describe a straightforward, rapid procedure based on bioinformatic analysis of a-helical coiled-coil motifs and peptide synthesis. With regard to the structural features and cellular location prediction of the proteins corresponding to the peptides selected for ADCI assays ( Table 1) , 15 of the proteins contain a pentapeptide conforming to the PEXEL consensus [19, 20; 21, 22] , but that none of these have a position within the amino acid sequence that conforms to the location of known active PEXEL motifs (see Materials and Methods and membrane segments, and none of them has a GPI anchor. In conclusion, an approach combining a genome-wide search by bioinformatics of a-helical coiled coil protein motifs and chemical synthesis can lead to the rapid identification and development of new malaria vaccine candidates. cache = ./cache/cord-048360-n9sih438.txt txt = ./txt/cord-048360-n9sih438.txt === reduce.pl bib === id = cord-033333-880jx1bt author = Salman, Saad title = In silico analysis of protein/peptide-based inhalers against SARS-CoV-2 date = 2020-10-08 pages = extension = .txt mime = text/plain words = 3431 sentences = 226 flesch = 53 summary = The molecular docking was performed for these inhalers including human neutralizing S230 light chain-antibody (monoclonal antibodies [mAbs]), alpha-1-antitrypsin (AAT), short-palate-lung and nasal-epithelial clone-1-derived peptides (SPLUNC1) and dornase-alfa (DA) against spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to assess their inhibitory activity. Protein-protein interaction (PPI) of COVID-19 spike glycoprotein with alpha-1-antitrypsin (1atu), dornase-alfa (4AWN), angiotensin-converting enzyme-2 (ACE-2) (PDB ID:1R4L), human palate, lung and nasal epithelium clone protein (SPLUNC1) (4n4x) and human neutralizing the S230 light chain antibody was evaluated through HawkDock. We attempted to address this issue by analyzing a variety of protein/peptide-based inhalers/antimucolytic agents and previously utilized mAb (used in asthma) to observe their possible interaction with the SARS-CoV-2 spike protein. • Molecular docking analysis of protein/peptide-based inhalers revealed that the S230 light chain antibody and dornase-alfa demonstrated a strong affinity for SARS-CoV-2 spike protein. cache = ./cache/cord-033333-880jx1bt.txt txt = ./txt/cord-033333-880jx1bt.txt === reduce.pl bib === id = cord-031957-df4luh5v author = dos Santos-Silva, Carlos André title = Plant Antimicrobial Peptides: State of the Art, In Silico Prediction and Perspectives in the Omics Era date = 2020-09-02 pages = extension = .txt mime = text/plain words = 16609 sentences = 954 flesch = 43 summary = 19 Plant AMPs are the central focus of the present review, comprising information on their structural features (at genomic, gene, and protein levels), resources, and bioinformatic tools available, besides the proposition of an annotation routine. 26 Plant AMPs are also classified into families considering protein sequence similarity, cysteine motifs, and distinctive patterns of disulfide bonds, which determine the folding of the tertiary structure. 27, 31 These AMP categories will be detailed in the next sections, together with other groups here considered (Impatienlike, Macadamia [β-barrelins], Puroindoline (PIN), and Thaumatin-like protein [TLP]) and the recently described αhairpinin AMPs. The description includes comments on their structure, pattern for regular expression (REGEX) analysis (when available), functions, tissue-specificity, and scientific data availability. 179 As to the TLP structure, this protein presents characteristic thaumatin signature (PS00316): 180, 181 Most of the TLPs have molecular mass ranging from 21 to 26 kDa, 163 possessing 16 conserved cysteine residues (Supplementary Figure S8) involved in the formation of 8 disulfide bonds, 182 which help in the stability of the molecule, allowing a correct folding even under extreme conditions of temperature and pH. cache = ./cache/cord-031957-df4luh5v.txt txt = ./txt/cord-031957-df4luh5v.txt === reduce.pl bib === id = cord-190540-zf5ksac2 author = Rakshit, Kausik title = An effective approach to reduce the penetration potential of Sars-Cov-2 and other viruses by spike protein: Through surface particle electrostatic charge negotiation date = 2020-06-18 pages = extension = .txt mime = text/plain words = 2065 sentences = 104 flesch = 46 summary = title: An effective approach to reduce the penetration potential of Sars-Cov-2 and other viruses by spike protein: Through surface particle electrostatic charge negotiation Reviewing the works of different authors, regarding charges, surface charge densities ({sigma}), charge mobility ({mu}) and electrostatic potentials of different aerosols under varied experimental conditions, a similar intensive study has also been carried out to investigate the electron donating and accepting (hole donating) properties of the spike proteins (S-proteins) of different RNA and DNA viruses, including SARS-COV-2. The electrostatic charges accumulated in the layers between the Gr IV Ge is sufficient enough to either fuse or repel the charges of the spike proteins of the RNA, DNA viruses including SARS-Cov-2 (RNA virus) or the aerosols. cache = ./cache/cord-190540-zf5ksac2.txt txt = ./txt/cord-190540-zf5ksac2.txt === reduce.pl bib === id = cord-193133-puqcbf8t author = Piplani, Sakshi title = In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus date = 2020-05-13 pages = extension = .txt mime = text/plain words = 3815 sentences = 215 flesch = 51 summary = The devastating impact of the COVID19 pandemic caused by SARS coronavirus 2 (SARSCoV2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in susceptibilities across animal species. Here we show how computational chemistry methods from structure-based drug design can be used to determine the relative binding affinities of the SARS-CoV-2 spike protein for its receptor, angiotensin converting enzyme (ACE)-2, a critical initiating event for SARS-CoV-2 infection, across multiple common and exotic animal species. 31, 32 Molecular docking was performed on the homology modelled SARS-CoV-2 spike protein with human and animal ACE2 proteins. The molecular dynamics simulation of complexes of SARS-CoV-2 spike protein and ACE2 receptors of various species were performed for 100ns. cache = ./cache/cord-193133-puqcbf8t.txt txt = ./txt/cord-193133-puqcbf8t.txt === reduce.pl bib === id = cord-103255-4k13re9y author = Daniell, Henry title = Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants date = 2001-05-01 pages = extension = .txt mime = text/plain words = 4362 sentences = 205 flesch = 42 summary = The production of recombinant proteins in plants has many potential advantages for generating biopharmaceuticals relevant to clinical medicine. In the decade since the expression and assembly of immunoglobulin (Ig) heavy and light chains into functional antibodies was first shown in transgenic tobacco, plants have proven to be versatile production systems for many forms of antibodies. Other advantages of tobacco include its relative ease of genetic manipulation, production of large numbers of seeds (up to a million per plant) and an impending need to explore alternate uses for this hazardous crop. However, the most attractive species for expressing subunit vaccine components should have high levels of soluble protein that is stable during storage; seed crops such as cereals are particularly suitable. Induction of a protective antibody response to foot and mouth disease in mice following oral or parenteral immunization with alfalfa transgenic plants expressing the viral structural protein VP1 cache = ./cache/cord-103255-4k13re9y.txt txt = ./txt/cord-103255-4k13re9y.txt === reduce.pl bib === id = cord-104282-90t1m430 author = nan title = Microsomal aldehyde dehydrogenase is localized to the endoplasmic reticulum via its carboxyl-terminal 35 amino acids date = 1994-09-02 pages = extension = .txt mime = text/plain words = 7076 sentences = 394 flesch = 53 summary = Abbreviations used in this paper: CAT, chloramphenicol acetyltransferase; FP2, NADPH-cytochrome P-450 reductase; msALDH, microsomal aldehyde dehydrogenase; PBS(+), PBS containing 1 mM CaCI2 and 0.5 mM MgCI2; PDI, protein disulfide isomerase; PTP, protein tyrosine phosphatase; STE, sucrose solution containing 10 mM Tris-HCl, pH 7.4, 1 mM EDTA, 10 t~g/ml leupepdn A, 0.5 mM PMSF, and 10 U/ml Trasyol; SRP, signal recognition particle. The nucleotide sequence predicts a polypeptide of 484 amino acids, and the most characteristic feature of this membrane-bound ALDH is carboxyl-terminal 35 amino acids, consisting of a stem region (amino acids 450-463) and a hydrophobic domain (amino acids 464-480) followed by a short hydrophilic tail region (amino acids 481-484) as shown in Fig. 1 . These data, together with those from subcellular fractionation, suggested that the carboxyl-terminal portion of msALDH including the hydrophobic sequence (amino acid 464-480) was necessary for both its ER localization and the tight association with the ER membrane. cache = ./cache/cord-104282-90t1m430.txt txt = ./txt/cord-104282-90t1m430.txt === reduce.pl bib === id = cord-150183-zzzyewjb author = Phillips, J. C. title = Synchronized Attachment and the Darwinian Evolution of Coronaviruses CoV-1 and CoV-2 date = 2020-08-27 pages = extension = .txt mime = text/plain words = 2483 sentences = 154 flesch = 55 summary = These are (CoV-1 site numbering from Uniprot P59594): 546Gln to Leu; 556 and 561Ser to Ala; and 568Ser to Leu. The differences associated with each of these mutations are hydropathically large (~50-100 in the MZ scale [4] ; all 20 amino acids span a range from most hydrophilic to most hydrophobic of 170). The central hydrophilic level set, absent from CoV-1 and present in CoV-2, is our main result ( There is an excellent review of the principles of self-organized criticality in living matter [3] . Some readers may be interested in the connections between hydropathic scaling theory of proteins and the more general synchronization of complex networks. Now that we are in the genomic age, with a very large sequence data base available for many proteins and many species, the discovery of these 20 fractals [5, 13] opens a new biophysics field of accurate thermodynamic analysis of small but medically important evolutionary differences. cache = ./cache/cord-150183-zzzyewjb.txt txt = ./txt/cord-150183-zzzyewjb.txt === reduce.pl bib === id = cord-103509-hynnba03 author = Wong, Ten-Tsao title = A self-assembled protein nanoparticle serving as a one-shot vaccine carrier date = 2020-09-18 pages = extension = .txt mime = text/plain words = 3187 sentences = 148 flesch = 48 summary = From these two clues, it was hypothesized that AH3-GFP fusion protein form stable protein complex through hydrophobic interaction mediated by N-terminal AH3 peptide. Using the same protocol, AH3-GFP was found to co-sedimented with the bacterial membrane (Fig. S3A) as well as the AH3-sfGFP-hM2e fusion protein but not a free GFP protein (Fig S3B) These results are consistent with our protein structure modeling that Arg11 serves as a main contact point for dimer stacking also it mediates the electrostatic interaction with mutated Glu13 (Fig. 3E ). These results suggest that the two point mutations of AH3 in I8L and K13E enable the formation of a stable, high antigenic protein complex that stimulates long lasting immune responses in a single immunization. The result suggests that although carrier protein AH3-sfGFP also has high antigenicity, it did not interfere with the immune response against the heterologous protein, hM2e (Fig. 5B, 5C) cache = ./cache/cord-103509-hynnba03.txt txt = ./txt/cord-103509-hynnba03.txt === reduce.pl bib === id = cord-253844-y6xdcf20 author = Yesudhas, Dhanusha title = COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics date = 2020-09-04 pages = extension = .txt mime = text/plain words = 7165 sentences = 422 flesch = 51 summary = In SARS-CoV-2 infection, intrinsically disordered regions are observed at the interface of the spike protein and ACE2 receptor, providing a shape complementarity to the complex. SUMMARY: The overall history and mechanism of entry of SARS-CoV-2 along with structural study of spike-ACE2 complex provide insights to understand disease pathogenesis and development of vaccines and drugs. The sequence similarity between SARS-CoV-2 and SARS-CoV spike proteins explains the possibility of binding to the same receptor angiotensin converting enzyme 2 (ACE2) in the host cell [14] . In this review, we discuss the history of coronaviruses in both humans and animals, their transmissions, mechanism of host cell entry and the structural studies, explaining active and inactive receptor binding of spike protein and the key residues playing an important role in the receptor binding. During viral infection, spike protein (~ 1300 amino acid residues) is cleaved by host proteases into receptor binding subunit S1 and membrane fusion subunit S2. cache = ./cache/cord-253844-y6xdcf20.txt txt = ./txt/cord-253844-y6xdcf20.txt === reduce.pl bib === id = cord-193489-u6ewlh16 author = Wang, Rui title = Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine date = 2020-04-29 pages = extension = .txt mime = text/plain words = 6066 sentences = 419 flesch = 62 summary = Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. Genetic identification and characterization of the geographic distribution, intercontinental evolution, and global trends of SARS-CoV-2 is the most efficient approach for studying COVID-19 genomic epidemiology and offer the molecular foundation for region-specific SARS-CoV-2 vaccine design, drug discovery, and diagnostic development [10] . We use K-means methods to cluster SARS-CoV-2 mutations, which provides the updated molecular information for the region-specific design of vaccines, drugs, and diagnoses. Table 5 presents the statistics of single mutations on various SARS-CoV-2 proteins that occurred in the recorded genomes between January 5, 2020, and April 24, 2020. Specifically, nucleocapsid protein has both the highest number of mutations per residues of 0.56 and the highest h-index of 27, suggesting that it is the most non-conservative protein in SARS-CoV-2 genomes. cache = ./cache/cord-193489-u6ewlh16.txt txt = ./txt/cord-193489-u6ewlh16.txt === reduce.pl bib === id = cord-254107-02bik024 author = Hillisch, Alexander title = Utility of homology models in the drug discovery process date = 2004-08-31 pages = extension = .txt mime = text/plain words = 7374 sentences = 374 flesch = 43 summary = The quality of these homology models, and thus their applicability to, for example, drug discovery, predominantly depends on the sequence similarity between the protein of known structure (template) and the protein to be modeled (target). In conjunction with homology models, Cengent Therapeutics (http://www.cengent.com) offers dynamic structural information generated from molecular dynamics simulations for 5500 human drug target proteins. If sequence identity is greater than ~50%, the resulting models are frequently of sufficient quality to be used in the prediction of detailed protein-ligand interactions, such as structure-based drug design and prediction of the preferred sites of metabolism of small molecules ( Figure 2 ). It has recently been shown that it is possible to design small molecules based on homology models and then to use these compounds as tools to study the physiological role of the respective target protein of that particular drug [31] . cache = ./cache/cord-254107-02bik024.txt txt = ./txt/cord-254107-02bik024.txt === reduce.pl bib === id = cord-253466-7gpije5d author = Netherton, Christopher title = A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication date = 2007-08-31 pages = extension = .txt mime = text/plain words = 26372 sentences = 1363 flesch = 45 summary = Significantly, Poliovirus infection causes enrichment of GEFs in membranes containing replicase proteins, and this would provide a mechanism for increasing levels of Arf1-GTP at sites of virus replication. There is evidence that Tobacco mosaic virus also uses the ER as a site of replication because the replicase enzyme and viral RNA are located on the ER of infected cells, and infection causes major changes in ER morphology (Reichel and Beachy, 1998) , including ER aggregation and formation of lamella structures. Even though these viruses infect a diverse range of hosts from different phyla, including vertebrates [poxviruses, African swine fever virus (ASFV)], arthropods (entomopox, ASFV, chloriridoviruses), amphibians and fish (Ranavirus, Megalocytivirus, and Lymphocystivirus genera of the Iridoviridae family), marine algae (phycodnaviruses), and protozoa (mimivirus), they all generate cytoplasmic factories as major sites of virus assembly and replication (illustrated in Fig. 4 ). Formation of DNA replication structures in herpes virus-infected cells requires a viral DNA binding protein cache = ./cache/cord-253466-7gpije5d.txt txt = ./txt/cord-253466-7gpije5d.txt === reduce.pl bib === id = cord-252536-gfx4cq03 author = Bieniossek, Christoph title = MultiBac: expanding the research toolbox for multiprotein complexes date = 2011-12-07 pages = extension = .txt mime = text/plain words = 7120 sentences = 354 flesch = 39 summary = It consists of an array of small synthetic DNA plasmids, an engineered baculovirus genome derived from the Autographa californica nuclear polyhedrosis virus (AcNPV; see Glossary) that is used to infect cells of the caterpillar Spodoptera frugiperda, and a set of protocols detailing every step from gene insertion into the plasmids to production of protein complexes in cultured insect cells [19, 20] . Donors and acceptors contain a resistance marker, a short imperfect inverted repeat (LoxP), an expression cassette consisting of a baculoviral promoter (p10 or polh), a DNA segment for inserting heterologous genes, and an efficient signal for eukaryotic polyadenylation (Figure 1a ). Two outstanding examples of the utility of MultiBac are the elegant production of the entire anaphase promoting complex, APC/Ca large (1.1 MDa) 13-subunit multiprotein assembly that regulates defined cell cycle transitions [34] and the recent crystal structure elucidation of the Mediator head modulea transcription factor complex that is essential for the expression of class II genes in eukaryotes [35] . cache = ./cache/cord-252536-gfx4cq03.txt txt = ./txt/cord-252536-gfx4cq03.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-252576-1ec545o2 author = Wu, Xiangli title = An antifungal defensin from Phaseolus vulgaris cv. ‘Cloud Bean’ date = 2011-01-15 pages = extension = .txt mime = text/plain words = 3562 sentences = 195 flesch = 55 summary = An antifungal peptide with a defensin-like sequence and exhibiting a molecular mass of 7.3 kDa was purified from dried seeds of Phaseolus vulgaris 'Cloud Bean'. After elution of unadsorbed proteins (fraction S1), adsorbed proteins were desorbed with a linear concentration (0-1 M) gradient of NaCl. The fraction with antifungal activity (S2) was then further fractionated by fast protein liquid chromatography on a Superdex 75 HR 10/30 column (GE Healthcare) in 0.2 M NH 4 HCO 3 buffer (pH 8.5). Antiproliferative activity toward tumor cells is also an attribute of defensins (Wong and Ng 2003) , defensin-like peptides and also other antifungal proteins including ribosome inactivating proteins (Lam et al. Some antifungal proteins including defensin-like peptides (Wong and Ng 2003) , protease inhibitors (Ye et al. The present findings on cloud bean defensin is reminiscent of the observation that mungin, an antifungal protein from mung beans, is without HIV-1 reverse transcriptase inhibitory activity (Ye and Ng 2000) . Concurrent purification of two defense proteins from French bean seeds: a defensin-like antifungal peptide and a hemagglutinin cache = ./cache/cord-252576-1ec545o2.txt txt = ./txt/cord-252576-1ec545o2.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-257584-v38tjof3 author = Fahmi, Muhamad title = Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV date = 2020-03-03 pages = extension = .txt mime = text/plain words = 2933 sentences = 180 flesch = 49 summary = Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. This was done using a combination of the phylogenetic tree constructed from the genome sequences and the cluster tree developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The phylogenetic analysis using complete genome sequences showed that 2019-nCoV was the most closely related to BatCoV RaTG13 and belonged to the Sarbecovirus subgenus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus (BAT-SL-CoVZXC21 and BAT-SL-CoVZC45) with the full support of reliability (Fig. 1) . Two (NS7b and NS8) of five nonstructural proteins were specific for 2019-nCoV and its closely related species, BatCoV RaTG13 and Bat-SARS-like coronavirus (BAT-SL-CoVZXC21 and BAT-SL-CoVZC45). cache = ./cache/cord-257584-v38tjof3.txt txt = ./txt/cord-257584-v38tjof3.txt === reduce.pl bib === === reduce.pl bib === id = cord-257392-u6jy6w1m author = Zhao, Yanfeng title = Proteomic analysis of primary duck hepatocytes infected with duck hepatitis B virus date = 2010-06-07 pages = extension = .txt mime = text/plain words = 6033 sentences = 294 flesch = 41 summary = In this report, we explored global changes in cellular protein expression in DHBV infected PDHs by two-dimension gel electrophoresis (2-DE) combined with MALDI-TOF/TOF tandem mass spectrometry (MS/MS). The down-regulated expression of beta-actin and annexin A2 was confirmed by Western blot analysis, and potential roles of some differentially expressed proteins in the virus-infected cells have been discussed. CONCLUSIONS: Differentially expressed proteins of DHBV infected PDHs revealed by 2-DE, are involved in carbohydrate metabolism, amino acid metabolism, stress responses and cytoskeleton processes etc, providing the insight to understanding of interactions between hepadnavirus and hepatocytes and molecular mechanisms of hepadnavirus pathogenesis. Expression levels of annexin A2, beta-actin, Hsp70, destrin, and lamin A were validated by Western blot analysis to confirm the dynamic alterations of protein expression during DHBV infection. In summary, the present study explored global changes in cellular protein expression of hepadnavirus infection by 2-DE analysis, using a natural DHBV-PDHs infection system. cache = ./cache/cord-257392-u6jy6w1m.txt txt = ./txt/cord-257392-u6jy6w1m.txt === reduce.pl bib === id = cord-257802-vgizgq2y author = Uttamchandani, Mahesh title = Applications of microarrays in pathogen detection and biodefence date = 2008-11-12 pages = extension = .txt mime = text/plain words = 6568 sentences = 305 flesch = 35 summary = Advances in miniaturizing this initial PCR step, for instance the development of Review Glossary Biodefence: defensive measures against biological threats, including natural/ emerging pathogens and bioterror agents, that have significant potential to endanger public health Detection: identifying the presence of target pathogen(s) from clinical or environmental samples. (b) Antibody microarrays can be used to detect pathogen proteins or antigens that might be present in environmental samples as an indication of contamination or for diagnostic purposes to determine pathogen infection in human tissues. fabricated a customized Affymetrix microarray containing 53 660 probes to detect DNA amplified from 18 different pathogenic microorganisms simultaneously, including pathogens from the US CDC's list of bioterrorism agents, such as Bacillus anthracis (which causes anthrax), Clostridium botulinum (which generates the botulinum toxin), Yersinia pestis (which causes bubonic plague) and the Ebola virus [17] . cache = ./cache/cord-257802-vgizgq2y.txt txt = ./txt/cord-257802-vgizgq2y.txt === reduce.pl bib === id = cord-254909-8zgvovu4 author = Srivastava, Rajneesh title = Serum profiling of leptospirosis patients to investigate proteomic alterations() date = 2012-12-05 pages = extension = .txt mime = text/plain words = 5745 sentences = 245 flesch = 29 summary = In this study, we have performed a proteomic analysis of serum samples from leptospirosis patients (n = 6), febrile controls (falciparum malaria) (n = 8) and healthy subjects (n = 18) to obtain an insight about disease pathogenesis and host immune responses in leptospiral infections. During the database search following parameters were specified: human taxonomy, trypsin digestion with one missed cleavage, carbamidomethyl (C) as fixed modification, oxidation (M) as variable modification, peptide mass tolerance set at 75 ppm and MS/MS tolerance of 0.4 Da. Western blot analysis was performed with serum samples from controls (healthy and febrile) and leptospirosis patients (n = 6) to validate the differential expression of some of the target proteins identified in 2DE and 2D-DIGE experiments. Aiming at analysis of host serum proteome alteration due to leptospirosis, we have identified several differentially expressed proteins and modulation of multiple physiological processes and pathways, including inflammation mediated acute phase responses, complement pathways, heterotrimeric G-protein signaling pathway, coagulation cascade and hemostasis in patients suffering from leptospiral infection. cache = ./cache/cord-254909-8zgvovu4.txt txt = ./txt/cord-254909-8zgvovu4.txt === reduce.pl bib === id = cord-006230-xta38e7j author = nan title = Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date = 2012-02-22 pages = extension = .txt mime = text/plain words = 135419 sentences = 7042 flesch = 43 summary = Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. cache = ./cache/cord-006230-xta38e7j.txt txt = ./txt/cord-006230-xta38e7j.txt === reduce.pl bib === id = cord-199630-2lmwnfda author = Ray, Sumanta title = Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs date = 2020-07-05 pages = extension = .txt mime = text/plain words = 6389 sentences = 379 flesch = 53 summary = Therefore, host-(1) We link existing high-quality, long-term curated and refined, large scale drug/protein -protein interaction data with (2) molecular interaction data on SARS-CoV-2 itself, raised only a handful of weeks ago, (3) exploit the resulting overarching network using most advanced, AI boosted techniques (4) for repurposing drugs in the fight against SARS-CoV-2 (5) in the frame of HDT based strategies. As for (3)-(5), we will highlight interactions between SARS-Cov-2-host protein and human proteins important for the virus to persist using most advanced deep learning techniques that cater to exploiting network data. As per our simulation study, a large fraction, if not the vast majority of the predictions establish true, hence actionable interactions between drugs on the one hand and SARS-CoV-2 associated human proteins (hence of use in HDT) on the other hand. cache = ./cache/cord-199630-2lmwnfda.txt txt = ./txt/cord-199630-2lmwnfda.txt === reduce.pl bib === === reduce.pl bib === id = cord-256325-q70rky3r author = Stewart, Cameron R. title = A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease date = 2017-07-04 pages = extension = .txt mime = text/plain words = 8310 sentences = 409 flesch = 43 summary = title: A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease Here we largely focus on findings from two recent RNAi screens to identify protein-coding genes and host-encoded microRNAs impacting the henipavirus infection cycle in human cells. X-ray data have suggested that the methylation of rRNA requires the formation of this complex with involvement of four fibrillarin molecules interacting with different regions of the target rRNAs. The yeast equivalent of fibrillarin, NOP1, has been more extensively studied than the human counterpart but fibrillarin is a well-conserved protein in most organisms, reinforcing the notion that all post-transcriptional processes involving fibrillarin such as chemical modification (methylation) of rRNA, pre-rRNA cleavage and ribosome assembly are essential for proper cellular functioning (Rodriguez-Corona et al. Deffrasnes and colleagues showed that siRNA-mediated knockdown of fibrillarin expression dramatically reduced HeV protein production and viral genome replication but did not impact viral fusion, and that fibrillarin catalytic activity was essential to henipavirus infection. cache = ./cache/cord-256325-q70rky3r.txt txt = ./txt/cord-256325-q70rky3r.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-258489-pyfc7jde author = Lico, Chiara title = Viral vectors for production of recombinant proteins in plants date = 2008-03-10 pages = extension = .txt mime = text/plain words = 11091 sentences = 527 flesch = 39 summary = In this review, we will focus on transient production strategies using plant viral expression systems, with a particular focus on the variety of proteins produced, and their applications. The unique properties of viruses such as ease of manipulation, high level amplification, site specific recombination, strong infectivity, enhanced translation and compact and repetitive morphological structure have enabled their broad application, from basic research to product development, including the generation of robust expression systems. From the discovery of viruses in 1898 (tobacco mosaic virus, TMV) (Bos, 1999) , to the first demonstration of RNAs role in virus replication by turnip yellow mosaic virus (TYMV) (Matthews, 1989) , to the very recent discovery of gene silencing and its implication in host response to infection, gene regulation and transgene expression (Baulcombe, 1999; Lu et al., 2003; Waterhouse and Helliwell, 2003) , plant virology has played a crucial role in the understanding of the most fundamental concepts of modern biology. Thanks to the recent improvements of viral-based vectors, mAbs have been produced with transient expression systems to quickly achieve much higher production levels along with other complex proteins. cache = ./cache/cord-258489-pyfc7jde.txt txt = ./txt/cord-258489-pyfc7jde.txt === reduce.pl bib === id = cord-258468-52gej3co author = Marcekova, Zuzana title = Heterologous expression of full-length capsid protein of porcine circovirus 2 in Escherichia coli and its potential use for detection of antibodies date = 2009-08-05 pages = extension = .txt mime = text/plain words = 6991 sentences = 326 flesch = 53 summary = title: Heterologous expression of full-length capsid protein of porcine circovirus 2 in Escherichia coli and its potential use for detection of antibodies coli-expressed Cap protein to self-assemble into virus-like particles (VLPs), the immunization of mice with recombinant Cap yielded antibodies with the same specificity as those raised against native PCV 2 virions. In addition, the antigenic properties of the purified Cap protein were employed in a subunit-based indirect ELISA to monitor the levels of PCV 2 specific antibodies in piglets originating from a herd which was experiencing PCV 2 infection. In order to eliminate the cluster of rare codons from the 5 end of the cap gene, the expression vector encoding a truncated variant of Cap protein ( Cap-His), which was lacking the first 16 amino acid residues, was constructed (Fig. 1B) . In summary, a bacterial expression system has been developed for the production of the full-length recombinant capsid protein of porcine circovirus type 2. cache = ./cache/cord-258468-52gej3co.txt txt = ./txt/cord-258468-52gej3co.txt === reduce.pl bib === id = cord-256340-w4z5avld author = Bailer, SM title = Connecting viral with cellular interactomes date = 2009-07-24 pages = extension = .txt mime = text/plain words = 3649 sentences = 167 flesch = 38 summary = Genome-scale screens for intraviral and virus–host protein interactions and the analysis of literature-curated datasets are able to provide a novel, comprehensive perspective of viruses, and virus-infected cells. Until now, large-scale interaction screens were predominantly performed with the yeast-two-hybrid (Y2H) system; however, alternative high-throughput technologies detecting binary protein interactions or protein complexes have been developed. The Y2H system as the standard assay for the evaluation of interactomes Essentially all high-throughput approaches to identify binary protein interactions on a genome-scale currently rely on the Gal4-based yeast-two-hybrid (Y2H) system ( Figure 1 ) developed in 1989 [1] . Despite certain limitations the Y2H system is used by the majority of groups because of its enormous efficacy and the data discussed in this review are all based on Y2H screens as all currently published large-scale studies on intraviral or virus-host protein interactions are based on them. More recent approaches on intraviral interactomes include several members of the herpesvirus family [15 ,16 ,19 Scheme of HSV-1 virus particle with protein interactions detected in a genome-wide Y2H screen. cache = ./cache/cord-256340-w4z5avld.txt txt = ./txt/cord-256340-w4z5avld.txt === reduce.pl bib === === reduce.pl bib === id = cord-261472-qcu73sdu author = Yao, Yong Xiu title = Cleavage and Serum Reactivity of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein date = 2004-07-01 pages = extension = .txt mime = text/plain words = 3851 sentences = 159 flesch = 47 summary = Severe acute respiratory syndrome (SARS) coronavirus (SCoV) spike (S) protein is the major surface antigen of the virus and is responsible for receptor binding and the generation of neutralizing antibody. To investigate SCoV S protein, full-length and individual domains of S protein were expressed on the surface of insect cells and were characterized for cleavability and reactivity with serum samples obtained from patients during the convalescent phase of SARS. The possible use of insect cell-displayed S protein for diagnostic application was assessed by examining fragment reactivity with serum samples from patients infected with human CoV 229E and also with serum from a patient with suspected but clinically unconfirmed SARS (serum sample 3118). Of the 2 assay formats we used, nondenatured S protein present on the cell surface provided the most sensitive detection of antibodies, with clear shifts in fluorescence for serum samples from patients with suspected but clinically unconfirmed SARS. cache = ./cache/cord-261472-qcu73sdu.txt txt = ./txt/cord-261472-qcu73sdu.txt === reduce.pl bib === id = cord-259505-7hiss0j3 author = Kong, Qingming title = Proteomic analysis of purified coronavirus infectious bronchitis virus particles date = 2010-06-09 pages = extension = .txt mime = text/plain words = 6907 sentences = 355 flesch = 44 summary = It is an important prerequisite for the functional studies to know the protein composition of the purified viral particles, as it allows the analysis of specific proteins and their roles during the virus life cycle, resulting in better understanding of the infection process and the pathogenesis of viruses. To date, there have been no reports about TENP associated with virus, but it's an enriched and abundant protein identified in purified infectious bronchitis particles which suggests to us that it may be a requisite host protein in IBV life cycles. The present study 1) provides the first proteomic analysis of infectious bronchitis particles, 2) establishes the most comprehensive proteomic index of IBV and 3) shows that most of the virion incorporated host proteins have central roles in virus life cycle. cache = ./cache/cord-259505-7hiss0j3.txt txt = ./txt/cord-259505-7hiss0j3.txt === reduce.pl bib === === reduce.pl bib === id = cord-262268-gm99cadh author = Wang, Jingqiang title = Assessment of Immunoreactive Synthetic Peptides from the Structural Proteins of Severe Acute Respiratory Syndrome Coronavirus date = 2003-12-01 pages = extension = .txt mime = text/plain words = 4027 sentences = 189 flesch = 49 summary = Consequently, we thoroughly investigated the immunoreactivities with patient sera of a series of synthesized peptides from SARS-coronavirus structural proteins. Results: Four epitopic sites, S599, M137, N66, and N371-404, located in the SARS-coronavirus S, M, and N proteins, respectively, were detected by screening synthesized peptides. The peptides representing the COOH terminus of the N protein, in particular N371 and N385, had high absorbance/cutoff value ratios with the highest positive detection rate and the lowest hydrophobicity score among all of the synthesized peptides (Fig. 1C, and Fig. 3 in the online Data Supplement). The other 17 peptides reacted only slightly with the sera from SARS patients and gave low detection rates, suggesting that the regions of the S protein covered by these peptides have no epitopic site. The patient sera preincubated with 4 mg/L S599 or N385 gave a 25-30% lower response in the ELISA (data not shown), suggesting that the two peptides could compete with SARS coronavirus for binding to the antibodies in SARS serum. cache = ./cache/cord-262268-gm99cadh.txt txt = ./txt/cord-262268-gm99cadh.txt === reduce.pl bib === id = cord-259603-bh198xgl author = Snijder, E.J. title = The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing date = 2016-09-14 pages = extension = .txt mime = text/plain words = 24187 sentences = 1090 flesch = 50 summary = Reverse-genetics studies targeting specific residues in SARS-CoV nsp7 confirmed the protein's importance for virus replication (Subissi et al., 2014b) , although the impact of single point mutations was smaller than anticipated on the basis of the biochemical characterization of the RNA-binding properties of nsp7-containing protein complexes in vitro (see later). The large number of viral subunits in these complexes (Subissi et al., 2014a) , the likely requirement for host factors (van Hemert et al., 2008) , and the concept of RNA synthesis occurring in a dedicated microenvironment in the infected cell (Knoops et al., 2008; V'Kovski et al., 2015) complicate the straightforward characterization of the CoV RdRp. To reconstitute the enzyme's activities in vitro, purified recombinant nsp12 is a key reagent but, for many years, such studies were hampered by poor nsp12 expression in Escherichia coli. cache = ./cache/cord-259603-bh198xgl.txt txt = ./txt/cord-259603-bh198xgl.txt === reduce.pl bib === id = cord-259260-qcfgigga author = Ibrahim, Ibrahim M. title = GRP78: A cell's response to stress date = 2019-06-01 pages = extension = .txt mime = text/plain words = 6837 sentences = 393 flesch = 50 summary = GRP78 expression is increased in cases of ER stressors like when the cell is abridged from sugar, treated with reagents that inhibit the process of protein glycosylation or disturb the intercellular calcium storage [5] . In the standard conditions of balance in the cell (homeostasis) GRP78 is bounded in an inactive form to Activating transcription factor 6 (ATF6), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and Inositol-requiring enzyme 1 (IRE1) which are UPR transmembrane stress sensors. According to the ligand or the peptide that bind to CS-GRP78, it will be activated in a defined signaling pathway that affects Besides, if the cell is cancerous, CS GRP78 will induce resistance to chemotherapy. Glucose regulated protein 78 (GRP78) inhibits apoptosis and attentinutes chemosensitivity of gemcitabine in breast cancer cell via AKT/mitochondrial apoptotic pathway De-regulation of GRP stress protein expression in human breast cancer cell lines Kringle 5 of human plasminogen induces apoptosis of endothelial and tumor cells through surface-expressed glucose-regulated protein 78 cache = ./cache/cord-259260-qcfgigga.txt txt = ./txt/cord-259260-qcfgigga.txt === reduce.pl bib === id = cord-261375-6fu3dzi9 author = Hoppe, Sebastian title = Microarray-based method for screening of immunogenic proteins from bacteria date = 2012-03-21 pages = extension = .txt mime = text/plain words = 6693 sentences = 389 flesch = 51 summary = Screening of expression libraries to expose novel antigens from bacteria often lead to an abundance of false positive signals owing to the high cross reactivity of polyclonal antibodies towards the proteins of the expression host. In this paper, we describe a method to covalently attach different HaloTag ® fusion proteins on HaloLink™ slides (see Figure 1 ) and consequently perform an immunoscreening using polyclonal antibodies in a microarray format, which is a suitable method for high-throughput applications such as screening of entire expression libraries (see Figure 2 ). Using our new method, we were able to express, immobilize and screen all of nine different proteins from Campylobacter jejuni using HaloTag ® and KRX cells. We were able to clone several genes from Campylobacter jejuni into KRX cells, to express the respective proteins as fusion constructs with a HaloTag ® attached to their N-Terminus and to immobilize these proteins on microarray surfaces. cache = ./cache/cord-261375-6fu3dzi9.txt txt = ./txt/cord-261375-6fu3dzi9.txt === reduce.pl bib === id = cord-262904-0b0ljjq1 author = Lon, Jerome Rumdon title = Prediction and evolution of B cell epitopes of surface protein in SARS-CoV-2 date = 2020-10-29 pages = extension = .txt mime = text/plain words = 5006 sentences = 263 flesch = 53 summary = It is worth mentioning that all 6 identified epitopes were conserved in nearly 3500 SARS-CoV-2 genomes, showing that it is helpful to obtain stable and long-acting epitopes under the condition of high frequency of amino acid mutation, which deserved further study at the experiment level. On this basis, we predicted the linear and conformational B cell epitopes, analyzed the conservation of the epitopes, the adaptability and other evolutionary characteristics of the surface protein, which provided a theoretical basis for the vaccine development and prevention of SARS-CoV-2. With the amino acid sequences of the surface protein of SARS-CoV-2 of NC_045512.2 as templates, we predicted the 3D structure of E and M protein through the online server SWISS-MODEL [10] based on homology modeling method, selected the optimal structure based on the template identity and GMQE value [10] , and the rationality of the structure was evaluated by Ramachandran plot [11] with PDBsum server. cache = ./cache/cord-262904-0b0ljjq1.txt txt = ./txt/cord-262904-0b0ljjq1.txt === reduce.pl bib === === reduce.pl bib === id = cord-264392-he1vekrt author = Lambeth, L. S. title = Complete genome sequence of Nariva virus, a rodent paramyxovirus date = 2008-12-23 pages = extension = .txt mime = text/plain words = 4363 sentences = 204 flesch = 52 summary = This study confirmed the classification of NarPV as a member of the subfamily Paramyxovirinae and established the close genome organization and sequence relationship between the two rodent paramyxoviruses isolated almost a decade apart and from two locations separated by more than 15,000 km. This was then followed by PCR to fill in the ''gaps'' using specific primers designed from NarPV Nariva virus genome 201 sequences obtained from the cDNA subtraction or degenerate primers designed using highly conserved consensus sequences of known paramyxoviruses in the subfamily Paramyxovirinae. Overall comparison of deduced sizes and amino acid sequences of all proteins indicated that NarPV is most closely related to MosPV (Table 1) genome is significantly larger (16,650 nt) than that of NarPV due to the longer untranslated regions (UTRs) located at the 3 0 end of most genes ( Fig. 1b and Table 1 ). cache = ./cache/cord-264392-he1vekrt.txt txt = ./txt/cord-264392-he1vekrt.txt === reduce.pl bib === id = cord-266543-ng9zr299 author = Klebe, Gerhard title = Virtual ligand screening: strategies, perspectives and limitations date = 2006-06-20 pages = extension = .txt mime = text/plain words = 11098 sentences = 527 flesch = 41 summary = In consequence, either the three-dimensional (3D) structure of the macromolecular target -as given by crystal structure analyses, NMR or sophisticated homology modelling -or, at the very least, a rigid reference ligand with a known bioactive conformation mapping out the putative receptor binding site must be available [5] . If one excludes purely retrospective studies, in which the potential of a method is demonstrated by its ability to enrich putatively active molecules from a sample of anticipated nonactive ones, 50 targets have been studied to date, and reports on the discovery of mostly micromolar binding ligands in a truly predictive fashion are available (Table 1) . With respect to VS, a unique and precise assignment of the protonation states of the ligand and protein functional groups in a pK a range between 3 and 11 is essential because, for example, for docking it is important whether such a group is considered as donor or acceptor of a hydrogen bond (Krämer and Klebe, unpublished). cache = ./cache/cord-266543-ng9zr299.txt txt = ./txt/cord-266543-ng9zr299.txt === reduce.pl bib === id = cord-258784-9bdd9krr author = Wei, Chiming title = New technology and clinical applications of nanomedicine: Highlights of the second annual meeting of the American Academy of Nanomedicine (Part I) date = 2006-12-31 pages = extension = .txt mime = text/plain words = 5540 sentences = 241 flesch = 33 summary = During the Presidential Lecture, Chiming Wei, MD, PhD, of Johns Hopkins University, summarized new published and unpublished findings and results in each nanomedicine research area, and also reviewed the new nanotechnologies and clinical applications in nanomedicine development. The significance of these investigations lies in the development of platform technologies including nanoscale molecular imaging, drug delivery, gene delivery, and diagnostic approaches. Dendrimer-based nanomedicine was developed for protein mimicry research, nanopharmaceuticals, diagnostic imaging with contrast agents, and targeted drug delivery in cancer cells. In Canada some of the important nanomedicine research areas include intelligent drug delivery systems; vaccine and gene delivery nanosystems; polymeric systems and devices; biochips; lab-on-achip; artificial cells; anti-cancer, immune-, neural-and musculoskeletal systems; nanoscale targeting; tissue and cellular engineering; novel biomaterials; and molecular imaging. For the junior YIA scientists, Jean-Christophe Rochet of Purdue University received first place for his work to develop nanoimaging-based approaches for detection and analysis of protein misfolding states. cache = ./cache/cord-258784-9bdd9krr.txt txt = ./txt/cord-258784-9bdd9krr.txt === reduce.pl bib === id = cord-256316-1odgm6hm author = Godet, Murielle title = TGEV corona virus ORF4 encodes a membrane protein that is incorporated into virions date = 1992-06-30 pages = extension = .txt mime = text/plain words = 5433 sentences = 269 flesch = 48 summary = Several lines of evidence lend support to the view that a gene encoding an SM-like protein is a common feature of the coronavirus genomes: (i) an ORF predicting a polypeptide with striking similarities to TGEV ORF4 was identified in the genome sequence of each of the 5 coronaviruses examined (Fig. 9 ) and the fact that TGEV SM was recognized by anti-FIPV antibodies argues for the presence of a related gene also in feline infectious peritonitis virus genome; (ii) the product expressed from the relevant MHV, BCV, and IBV ORFs was reported to have properties of a transmembrane polypeptide (Leibowitz et a/., 1988; Smith et al., 1990; Abraham et a/., 1990) ; and (iii) although expressed through a mono-, di-, or tricistronic mRNA (Abraham et a/., 1990; Budzilowicz and Weiss, 1987; Liu et al., 1991 ) the assumed SM-encoding genes are all located upstream and adjacent to the M protein gene. cache = ./cache/cord-256316-1odgm6hm.txt txt = ./txt/cord-256316-1odgm6hm.txt === reduce.pl bib === === reduce.pl bib === id = cord-262043-66qle52a author = Basit, Abdul title = Truncated human angiotensin converting enzyme 2; a potential inhibitor of SARS-CoV-2 spike glycoprotein and potent COVID-19 therapeutic agent date = 2020-05-20 pages = extension = .txt mime = text/plain words = 4866 sentences = 275 flesch = 55 summary = Spike (S) glycoprotein is the structural protein of SARS-CoV-2 located on the envelope surface, involve in interaction with angiotensin converting enzyme 2 (ACE2), a cell surface receptor, followed by entry into the host cell. The protein-protein docking and molecular dynamic simulation showed that tACE2 has higher binding affinity for RBD and form more stabilized complex with RBD than the intact ACE2. We designed a truncated version (tACE2) of ACE2 receptor covering the binding residues and performed protein-protein docking and molecular dynamic simulations to analyze its binding affinity for RBD and complex stability. Based on the HADDOCK score and the docking RMSD value, the docked complexes of ACE2 and tACE2 with RBD were analyzed for binding affinity DG (kcal mol À1 ) and stability using protein binding energy prediction (PRODIGY) server (Xue et al., 2016) . cache = ./cache/cord-262043-66qle52a.txt txt = ./txt/cord-262043-66qle52a.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-023026-2r84ndzv author = nan title = Posters date = 2013-06-14 pages = extension = .txt mime = text/plain words = 138458 sentences = 6513 flesch = 40 summary = Thus, this work provides the basis to identify molecular pathways regulated by distinct niche/environmental signals and involved in the heterogeneity of adult OPCs. Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS) characterized by inflammation, which leads to formation of demyelinating areas due to loss of oligodendrocytes, astrogliosis and, finally, axonal degeneration. Taken together, these results demonstrate the important role of miR-200b in modulating the MAPK pathway via c-Jun which in turn affects different aspects of the inflammatory process accompanying microglia activation including cytokine response, NO production, phagocytosis and neuronal cell death. For this purpose, coronal cryostat free-floating sections from the brain of both adult transgenic mice and their corresponding wild-type (Wt) littermates, were processed for the study of astrocytes using GFAP immunohistochemistry and microglia using antibodies against Iba1 and several markers commonly related to the activated phenotype of these microglial cells, such as CD16/32 (Fc receptor), F4/80, CD11b, CD206, CD150 and MHC-II. cache = ./cache/cord-023026-2r84ndzv.txt txt = ./txt/cord-023026-2r84ndzv.txt === reduce.pl bib === === reduce.pl bib === id = cord-265087-g4k6pc82 author = Munteanu, Cristian Robert title = Natural/random protein classification models based on star network topological indices date = 2008-10-21 pages = extension = .txt mime = text/plain words = 3890 sentences = 215 flesch = 52 summary = In conclusion, this study extends for the first time the classical TIs to protein star network TIs by proposing a model that can predict if a protein/fragment of protein is natural or random using only the amino acid sequence data. Using graphic approaches to study biological systems can provide useful insights, as indicated by many previous studies on a series of important biological topics, such as enzyme-catalyzed reactions (Andraos, 2008; Chou, 1989; Forsen, 1980, 1981; Chou and Liu, 1981; Chou et al., 1979; King and Altman, 1956; Kuzmic et al., 1992; Myers and Palmer, 1985; Zhou and Deng, 1984) , protein folding kinetics (Chou, 1990) , inhibition kinetics of processive nucleic acid polymerases and nucleases (Althaus et al., 1993a (Althaus et al., , b, c, 1994a (Althaus et al., , b, 1996 Chou et al., 1994) , analysis of codon usage (Chou and Zhang, 1992; Chou, 1993, 1994) , base frequencies in the anti-sense strands , and analysis of DNA sequence (Qi et al., 2007) . cache = ./cache/cord-265087-g4k6pc82.txt txt = ./txt/cord-265087-g4k6pc82.txt === reduce.pl bib === id = cord-261159-9pkg7mbh author = Regnier, Fred E. title = Chromatography of complex protein mixtures date = 1987-07-17 pages = extension = .txt mime = text/plain words = 10934 sentences = 565 flesch = 51 summary = Although large amounts of organic solvent are occasionally used in the mobile phase to solubilize proteins, as in the case of chloroplast proteins [ 181, most IEC separations are carried out with either non-ionic detergents or the 3-[ ( 3-chloroamidopropyl) dimethylammonio] -l-trifluoroacetic acid ( CHAPS) zwitterion [ 24,251. Using a series of polyethylene glycol alkyl ether (C,E,) detergents as a mobile phase additive it was possible to show that both alkyl chain length and the number of glycol residues influenced resolution of Escherichiu coZi K-12 membrane proteins in anion-exchange separations [ 191 (C&E, was optimal) . Elution of proteins and peptide fragments from RPC columns was achieved with mobile phases containing 5% formic acid. In the case of red blood cell membrane proteins, the resolution of 1000 A pore diameter organic resin-based sorbents was superior to 300 A pore diameter silica-based materials when the columns were eluted with a TFA-acetonitrile mobile phase [ 261. cache = ./cache/cord-261159-9pkg7mbh.txt txt = ./txt/cord-261159-9pkg7mbh.txt === reduce.pl bib === === reduce.pl bib === id = cord-266481-9afb0yvt author = Naskalska, Antonina title = Membrane Protein of Human Coronavirus NL63 Is Responsible for Interaction with the Adhesion Receptor date = 2019-07-17 pages = extension = .txt mime = text/plain words = 5673 sentences = 289 flesch = 51 summary = We have previously shown that the virus uses heparan sulfate proteoglycans (HSPGs) as the initial attachment factors, facilitating viral entry into the cell. However, we recently reported that heparan sulfate (HS) proteoglycans (HSPGs) are required for effective adhesion of the virus to the cell surface and that such an interaction enhances the infection process (12) . To further validate this result, we blocked the virus-ACE2 interaction with anti-ACE2 antibody, which resulted in inhibition of MENS VLP internalization but not adhesion to the cell surface (Fig. 3) . Using flow cytometry, we next investigated whether the adhesion of MEN and MENS VLPs to the cell surface involves interaction with HSPGs, as has been shown for HCoV-NL63. Mapping of the receptor-binding domain and amino acids critical for attachment in the spike protein of avian coronavirus infectious bronchitis virus cache = ./cache/cord-266481-9afb0yvt.txt txt = ./txt/cord-266481-9afb0yvt.txt === reduce.pl bib === === reduce.pl bib === id = cord-264031-0y7xbgun author = Wierbowski, Shayne D. title = A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date = 2020-10-13 pages = extension = .txt mime = text/plain words = 5066 sentences = 291 flesch = 42 summary = title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. Further, we explore the utility of our interactome modeling approach in identifying key 99 interactions undergoing evolution along viral protein interfaces, highlighting population variants on 100 human interfaces that could modulate the strength of viral-host interactions to confer protection from or 101 susceptibility to COVID-19, and prioritizing drug candidates predicted to bind competitively at viral-102 human interaction interfaces. cache = ./cache/cord-264031-0y7xbgun.txt txt = ./txt/cord-264031-0y7xbgun.txt === reduce.pl bib === === reduce.pl bib === id = cord-267475-6f4h3cck author = Kozak, Marilyn title = Pushing the limits of the scanning mechanism for initiation of translation date = 2002-10-16 pages = extension = .txt mime = text/plain words = 24538 sentences = 1234 flesch = 50 summary = This depends on careful structural arrangements, however, which are rarely present in cellular mRNAs. Understanding the rules for initiation of translation enables understanding of human diseases in which the expression of a critical gene is reduced by mutations that add upstream AUG codons or change the context around the AUG(START) codon. (Whether the second AUG codon resides in a strong or weak context is not relevant; the ribosome reads the mRNA linearly and thus the decision to stop or to bypass the first AUG is not influenced by whether there is a better initiation site downstream.) The large number of genes that employ leaky scanning precludes discussion of the biological significance of the proteins thereby produced, but it merits noting that, for many of the viruses in Table 3 , replication requires production of both listed proteins. cache = ./cache/cord-267475-6f4h3cck.txt txt = ./txt/cord-267475-6f4h3cck.txt === reduce.pl bib === id = cord-260440-e63pgcir author = Dinjaski, Nina title = Smart polyhydroxyalkanoate nanobeads by protein based functionalization date = 2015-02-24 pages = extension = .txt mime = text/plain words = 9066 sentences = 520 flesch = 35 summary = In vivo PHA modification based on peptide functionalization of PHA nano-beads using GAPs for recombinant protein anchoring to the PHA granule or nonspecific binding and in vivo chemical modification through incorporation of functional group in the side chain of the polymer applying metabolic engineering and systems biology approach. 30 The main advantages of this in vitro cell-free system are: i) the possibility of tight control of nanoparticle disassembly and reassembly process; ii) absence of competition among the recombinant GAP-fusion and wild type proteins; iii) tight control over particle size and immobilized protein/active agent concentration; iv) possibility of endotoxin removal, crucial for the design of every biomedical setup. 18 In completely different context to in vivo tag binding, in vitro synthesized PHA nanoparticles and in vitro hydrophobic binding of PhaP fusion proteins with protein ligands (e.g., mannosylated human α1-acid glycoprotein (hAGP) and human epidermal growth factor (hEGF)) have been reported as another outstanding application of phasins for receptor-mediated drug delivery. cache = ./cache/cord-260440-e63pgcir.txt txt = ./txt/cord-260440-e63pgcir.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-270594-62xotol3 author = He, Lei title = Identification and characterization of vp7 gene in Bombyx mori cytoplasmic polyhedrosis virus date = 2017-09-05 pages = extension = .txt mime = text/plain words = 4444 sentences = 266 flesch = 55 summary = In this study, the viral structural protein 7 (VP7) polyclonal antibody was prepared with immunized mouse to explore the presence of small VP7 gene-encoded proteins in Bombyx mori cytoplasmic polyhedrosis virus. The replication of BmCPV genome in the cultured cells and midgut of silkworm was decreased by reducing the expression level of vp7 gene using RNA interference. In immunoprecipitation experiments, using a polyclonal antiserum directed against the VP7, one additional shorter band in BmCPV infected midguts was detected, and then the band was analyzed with mass spectrum (MS), the MS results showed thatone candidate interacted protein (VP7 voltage-dependent anion-selective channel-like isoform, VDAC) was identified from silkworm. A novel protein was detected from the overexpression of vp7 gene in the BmCPV infected cultured cells, with VP7 antibody. Total proteins from the BmCPV infected silkworm midguts (from the first day to the twelfth day) were also extracted, and detected with VP7 antibody. cache = ./cache/cord-270594-62xotol3.txt txt = ./txt/cord-270594-62xotol3.txt === reduce.pl bib === id = cord-260869-rym2ik0o author = Lemmermeyer, Tanja title = Characterization of monoclonal antibodies against feline coronavirus accessory protein 7b date = 2016-02-29 pages = extension = .txt mime = text/plain words = 6482 sentences = 389 flesch = 58 summary = The 7b protein has a molecular mass of $26 kDa, it is secreted from the cell and contains (i) a Cterminal KDEL-like endoplasmic reticulum (ER) retention signal, (ii) an N-terminal signal sequence of 17 amino acids and (iii) a potential N-glycosylation site at aa position 68 (Vennema et al., 1992a) . The identity of the purified protein was confirmed by SDS-PAGE and Western blotting using anti-His mAb. The protein had an apparent molecular mass of 24 kDa as judged by SDS-PAGE analysis, which is predicted for this protein, and was recognized by the His-tag-specific antibody (Fig. 1a) . Two additional minor bands in the SDS-PAGE were specifically recognized by Western blotting using the His-tag-specific mAb. These bands are consistent with a dimer and a 37-kDa degradation product, respectively, of the GST-7bDSS-His protein (Fig. 1b) . The results outlined above show that the anti-7b mAbs recognize exclusively the nonglycosylated form of the viral protein in FCoV-infected cells. cache = ./cache/cord-260869-rym2ik0o.txt txt = ./txt/cord-260869-rym2ik0o.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-274080-884x48on author = Rumlová, Michaela title = In vitro methods for testing antiviral drugs date = 2018-06-30 pages = extension = .txt mime = text/plain words = 17989 sentences = 941 flesch = 41 summary = For the majority of animal viruses, the activation of these fusion or penetration mechanisms occurs through conformational changes and structural rearrangements in viral surface proteins and/or the whole virion shell that may destabilize the capsid core. D: Three mechanisms (I.-III.) of DNA viruses replication are shown: (I): Following entry and uncoating, the DNA genome is transported to the nucleus; products of early genes (regulatory proteins, transcription factors) regulate the synthesis of viral enzymes (e.g. DNA polymerase) required for genome replication; expression of late genes encoding structural capsid proteins in the cytosol, they are then transported into nucleus where packaging and pre-assembly take place; preassembled procapsids exit the nucleus and leave the cell (e.g. Herpesviruses). Here, we provide an overview of in vitro methods, including cell-based assays, that may be suitable for screening of antivirotics that interfere with the key steps of viral life cycles and target either virus or cell-encoded proteins required for the infectivity. cache = ./cache/cord-274080-884x48on.txt txt = ./txt/cord-274080-884x48on.txt === reduce.pl bib === id = cord-266617-z8uecyl6 author = Pavesi, Angelo title = Asymmetric evolution in viral overlapping genes is a source of selective protein adaptation date = 2019-04-03 pages = extension = .txt mime = text/plain words = 6677 sentences = 326 flesch = 52 summary = Analysis of nucleotide and amino acid sequences revealed that half of overlaps undergo asymmetric evolution, as the protein from one frame shows a number of substitutions significantly higher than that of the protein from the other frame. I classified a pair of homologous overlaps as a case of symmetric evolution, if the number of amino acid substitutions in the Up1-Up2 alignment did not significantly differ from that in the Down1-Down2 alignment (chi-square < 3.84). In alternative, I classified a pair of homologous overlaps as a case of asymmetric evolution, if the number of amino acid substitutions in the Up1-Up2 alignment was significantly different from that in the Down1-Down2 alignment (chi-square > 3.84). The analysis of the pattern of nucleotide substitutions in the 75 pairs of homologous overlaps revealed 39 and 36 cases of symmetric and asymmetric evolution, respectively (Supplementary Table S2 ). cache = ./cache/cord-266617-z8uecyl6.txt txt = ./txt/cord-266617-z8uecyl6.txt === reduce.pl bib === === reduce.pl bib === id = cord-274056-9t3kneoo author = Abd Elwahaab, Marwa A. title = A Statistical Similarity/Dissimilarity Analysis of Protein Sequences Based on a Novel Group Representative Vector date = 2019-05-08 pages = extension = .txt mime = text/plain words = 3314 sentences = 251 flesch = 59 summary = title: A Statistical Similarity/Dissimilarity Analysis of Protein Sequences Based on a Novel Group Representative Vector For beta globin protein sequences, seven species are selected in our sample set: human, chimpanzee, gorilla, mouse, rat, gallus, and opossum, as illustrated in Table 1 . The similarity/dissimilarity vectors that are corresponding to beta globin, ND5, and spike protein sequences are illustrated in Tables 9, 10, and 11, respectively, based on the two methods discussed before. The results in Table 10 show that both the magnitude ( 5 ) and the angle ( 5 ) can measure similarity/dissimilarity degree well among ND5 protein sequences as shown in Figure 2 . The similarity/dissimilarity analysis among the seven beta globin sequences measured according to ( 5 ) is illustrated in Table 12 and shown in Figure 4 . The similarity/dissimilarity analysis among the beta globin sequences measured according to (GR spike ) is illustrated in Table 14 and shown in Figure 6 . cache = ./cache/cord-274056-9t3kneoo.txt txt = ./txt/cord-274056-9t3kneoo.txt === reduce.pl bib === id = cord-274366-t138l6px author = Benetti, Elisa title = ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population date = 2020-07-17 pages = extension = .txt mime = text/plain words = 4525 sentences = 247 flesch = 49 summary = Taking advantage of the Network of Italian Genomes (NIG), a consortium established to generate a public database (NIG-db) containing aggregate variant frequencies data for the Italian population (http://www.nig.cineca.it/), here we describe the genetic variation of ACE2 in the Italian population, one of the newly affected countries by the SARS-CoV-2 outbreak causing COVID-19. In order to shed light on the role of ACE2 variants on interindividual variability and susceptibility to COVID-19 in Italian population we performed WES analysis on a cohort of 131 patients and 258 controls who agreed in participating to the study (see "Materials and methods"). These variants which surround residual essentials for the SARS-CoV-2 spike protein binding were predicted to likely affect the cleavage-dependent virion intake, such as the polymorphic c.2158A>G p.(Asn720Asp) (allele frequency 0.011) which lies four amino acids from the cleavage sequence of TMPRSS2 or to have a substantial impact on protein structure and spike protein interaction by MD simulation (Fig. 3a) . cache = ./cache/cord-274366-t138l6px.txt txt = ./txt/cord-274366-t138l6px.txt === reduce.pl bib === id = cord-262119-s6hc7fxs author = Ostaszewski, Marek title = COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date = 2020-10-27 pages = extension = .txt mime = text/plain words = 12332 sentences = 742 flesch = 38 summary = title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms The molecular pathophysiology that links SARS-CoV-2 infection to the clinical manifestations and course of COVID-19 is complex and spans multiple biological pathways, cell types and organs [2, 3] . With this goal in mind, we initiated a collaborative effort involving over 230 biocurators, domain experts, modelers and data analysts from 120 institutions in 30 countries to develop the COVID-19 Disease Map, an open-access collection of curated computational diagrams and models of molecular mechanisms implicated in the disease [4] . The COVID-19 Disease Map diagrams, available in layout-aware systems biology formats and integrated with external repositories, are available in several formats allowing a range of computational analyses, including network analysis and Boolean, kinetic or multiscale simulations. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms cache = ./cache/cord-262119-s6hc7fxs.txt txt = ./txt/cord-262119-s6hc7fxs.txt === reduce.pl bib === id = cord-273019-hbpfz8rt author = Glingston, R. Sahaya title = Organelle dynamics and viral infections: at cross roads date = 2018-06-25 pages = extension = .txt mime = text/plain words = 9513 sentences = 486 flesch = 35 summary = Studies on the herpes simplex virus-1 (HSV-1) infection on Vero, BHK-21 and PtK 2 cells reported transportation of viral tegument-capsid by dynein to the cytoplasmic side of NPC [22, 23] . In order to construct these compartments, viruses alter host's fatty acid metabolism, induce rearrangement of the membrane constituents and also recruit cellular machinery to produce proteins essential for its replication [59, 60] . Upregulation of mitophagy and degradation of the mitochondrial antiviral signalling protein (MAVS) in order to attenuate the antiviral immune response in non-small cell lung cancer (NSCLC) cells was reported upon measles virus infection [83] . The expression of matrix protein (M) of human parainfluenza virus type 3 (HPIV3) in HEK293T and HeLa cells was reported to induce mitophagy resulting in the suppression of type1 interferon response [84] . Many viruses or viral proteins are reported to localize to peroxisomes and/or exploit their functions to facilitate their replication in the host cells [108] . cache = ./cache/cord-273019-hbpfz8rt.txt txt = ./txt/cord-273019-hbpfz8rt.txt === reduce.pl bib === id = cord-268326-sbz3uk5h author = Bonam, Srinivasa Reddy title = Lysosomes as a therapeutic target date = 2019-09-02 pages = extension = .txt mime = text/plain words = 17899 sentences = 839 flesch = 37 summary = With a focus on lysosomal dysfunction in autoimmune disorders and neurodegenerative diseases — including lupus, rheumatoid arthritis, multiple sclerosis, Alzheimer disease and Parkinson disease — this Review critically analyses progress and opportunities for therapeutically targeting lysosomal proteins and processes, particularly with small molecules and peptide drugs. Alterations in lysosomal functions, either in the fusion processes involved in the general pathways mentioned above or related to the function of lyso somal enzymes and non enzymatic proteins, can result in broad detrimental effects, including failure to clear potentially toxic cellular waste, inflammation, apopto sis and dysregulation of cellular signalling 8 . cache = ./cache/cord-268326-sbz3uk5h.txt txt = ./txt/cord-268326-sbz3uk5h.txt === reduce.pl bib === id = cord-277811-j58qvyum author = Mehrani, Hossein title = Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis date = 2011-01-07 pages = extension = .txt mime = text/plain words = 4086 sentences = 226 flesch = 51 summary = title: Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis Haptoglobin α1 chain isoforms (spots 21, 22 and 23) were only detected in the plasma of the severe lung diseases patients but were not detectable in healthy controls ( Figure 2B and 2C). In this study we present plasma proteome analysis of SM exposed patients compared to the healthy controls. In our recent study of BAL fluid proteomics patterns in SM exposed patients we also found that haptoglobin isoforms were significantly elevated in moderate and severe lung disease patients compared to mild and healthy controls [13] . In conclusion, this study complements our previous BAL fluid proteome analysis of patients exposed to SM gas which resulted in identification of number of differentially expressed proteins. Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis cache = ./cache/cord-277811-j58qvyum.txt txt = ./txt/cord-277811-j58qvyum.txt === reduce.pl bib === id = cord-269011-230p8rsf author = de Haan, Cornelis A.M. title = Molecular Interactions in the Assembly of Coronaviruses date = 2005-08-31 pages = extension = .txt mime = text/plain words = 22956 sentences = 1052 flesch = 46 summary = Biochemical and theoretical studies led to a topological model for the MHV M protein Rottier et al., 1984 Rottier et al., , 1986 , in which the polypeptide spans the lipid bilayer three times, leaving a small amino-terminal domain (15-35 residues) in the lumen of intracellular organelles (or outside the virus), whereas the carboxyterminal half of the protein is located on the cytoplasmic side of the membrane (or inside the virion). Using a mutational approach including deletions, insertions, and substitutions, both the transmembrane domain and the cysteine-rich region immediately downstream thereof, but not the carboxy-terminal part of the cytoplasmic tail, were shown to be important for MHV S protein-induced cell-cell fusion (Bos et al., 1995; Chang and Gombold, 2001; Chang et al., 2000) The cleavage requirements of the S proteins for the biological activities of the coronavirus spike remain enigmatic. cache = ./cache/cord-269011-230p8rsf.txt txt = ./txt/cord-269011-230p8rsf.txt === reduce.pl bib === id = cord-270273-a4iu9qg6 author = Ruiz, Federico M. title = Chicken GRIFIN: Structural characterization in crystals and in solution date = 2017-12-15 pages = extension = .txt mime = text/plain words = 8271 sentences = 386 flesch = 48 summary = The case study on galectins (b-galactoside-binding proteins with b-sandwich fold and a sequence signature responsible for ligand contact [5] ) is describing such a network with overlapping and distinct expression profiles [6e8]. In this study, the availability of crystals of the same protein obtained at different conditions documents the very low degree of influence of the pH value on the galectin fold, with some variability in unit cell Looking closely at the interface region between the two subunits of C-GRIFIN's homodimer, it is established by the F1/S1 strands from the N-and C-termini of each subunit in the homodimer (residues 4e14/127-136) (Fig. 4B) . Taking analysis of C-GRIFIN and lactose binding again to the level of a solution in this report, measuring extent and profile of HDX in the absence and presence of ligand can identify the contact site. cache = ./cache/cord-270273-a4iu9qg6.txt txt = ./txt/cord-270273-a4iu9qg6.txt === reduce.pl bib === id = cord-276456-oa6hh7ky author = Collins, R.N. title = 5.14 The Biophysics of Membrane Fusion date = 2012-05-03 pages = extension = .txt mime = text/plain words = 9156 sentences = 448 flesch = 44 summary = It will be challenging to distinguish between the lipid simply being a scaffold for a multitude of proteins involved with trafficking at the plasma membrane, and having a direct function in the bilayer rearrangements of fusion and fission. 38 The requirements for specific amino acids at certain positions and for a defined length in the fusion peptide have been further supported by the NMR-solved structure of fusion peptide in detergent micelles and in model lipid membranes 43,52 stabilized by a charge-dipole interaction between the N-terminal Gly and the dipole moment of helix 2 54 (Figure 6 ). The energetics and topology of SNARE complex formation may influence local bending of the a-helix at the interfacial region, which in turn could generate local membrane destabilization to aid fusion ( Figure 8) . How conformational changes amongst SNARE proteins and their accessory factors control the thermodynamics and kinetics of docking, lipid mixing and content mixing after membrane fusion remain open questions. cache = ./cache/cord-276456-oa6hh7ky.txt txt = ./txt/cord-276456-oa6hh7ky.txt === reduce.pl bib === id = cord-264996-og3sg0qw author = Howell, Gareth J. title = Cell Biology of Membrane Trafficking in Human Disease date = 2006-09-17 pages = extension = .txt mime = text/plain words = 20320 sentences = 1072 flesch = 42 summary = Many of these transport intermediates or vesicles, whether derived from the ER, other internal organelles, or the plasma membrane, are ''coated'' with unique protein complexes, tethering factors, and regulatory factors that ensure correct targeting to an acceptor compartment. Breast cancer Caveolin-1 Deletion or dominant negative mutation of caveolin-1 promotes tumor progression Breast cancer (Bouras et al., 2004; Williams and Lisanti, 2005) (Hayasaka et al., 1993; Matsuyama et al., 2002) Chediak-Higashi syndrome (CHS) CHS1/Lyst Lyst involved in regulation of protein secretion from lysosomes -enlarged lysosomes Partial albinism, recurrent bacterial infections, impaired chemotaxis and abnormal natural killer cell function (Shiflett et al., 2002; Ward et al., 2003) 214500 Choroideremia (CHM) Rab Escort Protein 1 (REP1) RAB27a remains cytosolic due to defective geranylgeranyl modification in CHM lymphoblasts X-linked form of retinal degeneration 303100 Various mechanisms control the traYcking of proteins from the TGN by the formation and delivery of membrane-derived transport vesicles to the plasma membrane, endosomes, or lysosomal structures (Ponnambalam and Baldwin, 2003) . cache = ./cache/cord-264996-og3sg0qw.txt txt = ./txt/cord-264996-og3sg0qw.txt === reduce.pl bib === id = cord-276966-wmelyonk author = Roe, Kevin title = A proposed treatment for pathogenic enveloped viruses having high rates of mutation or replication date = 2020-07-08 pages = extension = .txt mime = text/plain words = 5242 sentences = 242 flesch = 44 summary = In targeting specific viral pathogens, dual-protein ligand masks (for brevity, henceforth called dualprotein ligands) should be able to create a quick and powerful immune memory response with existing memory immune cells against some viral pathogens or virus infected cells, without some of the practical limitations of vaccines. Dual-protein ligands could induce an immune response by mimicking the key parts of antigens that activate existing immune memory cells or innate immune cells to attack tagged viral pathogens. All rights reserved One treatment option injects dual-protein ligands into the blood stream or localized regions to mask pathogenic surface proteins used by viruses to infect mammalian cells. Targeted dual-protein ligands could mask viral surface proteins to quickly treat some untreatable virus infections by using already existing immune cells. cache = ./cache/cord-276966-wmelyonk.txt txt = ./txt/cord-276966-wmelyonk.txt === reduce.pl bib === id = cord-279418-3r1ijafm author = Nevers, Quentin title = Negri bodies and other virus membrane-less replication compartments() date = 2020-08-21 pages = extension = .txt mime = text/plain words = 6437 sentences = 406 flesch = 44 summary = We particularly examine the interplay between viral factories and the cellular innate immune response, of which several components also form membrane-less condensates in infected cells. With the rapid identification of cellular membraneless compartments and proteins that undergo LLPS in vitro, a major challenge in the field is to demonstrate unambiguously that a specific structure is indeed a phase-separated liquid body in the cellular context. Until now, only a few specific cellular factors, which directly interact with viral proteins such as the nucleoproteins and phosphoproteins of MNV, have been shown to concentrate in these structures. Upon Infection, Cellular WD Repeat-Containing Protein 5 (WDR5) Localizes to Cytoplasmic Inclusion Bodies and Enhances Measles Virus Replication The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression The Cellular Protein CAD is Recruited into Ebola Virus Inclusion Bodies by the Nucleoprotein NP to Facilitate Genome Replication and Transcription cache = ./cache/cord-279418-3r1ijafm.txt txt = ./txt/cord-279418-3r1ijafm.txt === reduce.pl bib === id = cord-275993-isff6lp2 author = Han, Dong P title = Development of a safe neutralization assay for SARS-CoV and characterization of S-glycoprotein date = 2004-08-15 pages = extension = .txt mime = text/plain words = 5598 sentences = 308 flesch = 52 summary = Similar to other coronaviruses, spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. S-protein of coronaviruses, which is thought to function as a trimer (Delmas and Laude, 1990) , is responsible for both binding to cellular receptors and inducing membrane fusion for virus entry into target cells (Collins et al., 1982; Godet et al., 1994; Kubo et al., 1994) . Despite difficulties in detecting S-protein directly by immunoassays, proteins expressed from both pcDNA-S and pHCMV-S constructs were able to pseudotype MuLV particles to produce SARS pseudoviruses that could readily infect Vero E6 cells (Fig. 3A) . To assess whether SARS pseudoviruses we generated could be used to quantify virus-neutralizing antibodies, we examined their susceptibility to convalescent sera from SARS-CoV-infected patients. Pseudotyping of murine leukemia virus with the envelope glycoproteins of HIV generates a retroviral vector with specificity of infection for CD4-expressing cells cache = ./cache/cord-275993-isff6lp2.txt txt = ./txt/cord-275993-isff6lp2.txt === reduce.pl bib === id = cord-270587-k56fze59 author = Scherbinina, Sofya I. title = Three-Dimensional Structures of Carbohydrates and Where to Find Them date = 2020-10-18 pages = extension = .txt mime = text/plain words = 12390 sentences = 819 flesch = 34 summary = • Database can be freely accessed through web user interface; • Database must contain experimentally confirmed and/or predicted 3D structures (preprocessed and/or generated on-the-fly from a primary structure input) of glycans, glycoproteins, or protein-carbohydrate complexes; • Stored 3D structures must be deposited as atomic coordinates in PDB, MOL, or other format, and the structures must contain a saccharide moiety; • • Database can be freely accessed through web user interface; • Database must contain experimentally confirmed and/or predicted 3D structures (preprocessed and/or generated on-the-fly from a primary structure input) of glycans, glycoproteins, or protein-carbohydrate complexes; • Stored 3D structures must be deposited as atomic coordinates in PDB, MOL, or other format, and the structures must contain a saccharide moiety; • Currently, CHARMM36 parameterization features include monosaccharides in furanose [171] and pyranose [172] forms, glycosidic linkages between monosaccharides [171, 173] , complex carbohydrates and glycoproteins Detailed comparisons of all-chemical and dedicated force fields in a context of glycan modeling have been published [114, 139, 151, 167] . cache = ./cache/cord-270587-k56fze59.txt txt = ./txt/cord-270587-k56fze59.txt === reduce.pl bib === id = cord-268416-8hw80qx8 author = Grunewald, Matthew E. title = The coronavirus nucleocapsid protein is ADP-ribosylated date = 2018-04-01 pages = extension = .txt mime = text/plain words = 4795 sentences = 263 flesch = 50 summary = While screening for ADP-ribosylated proteins during coronavirus (CoV) infection, we detected a ~55 kDa ADP-ribosylated protein in mouse hepatitis virus (MHV)-infected cells and in virions, which we identified as the viral nucleocapsid (N) protein. To identify potential targets of the CoV macrodomain, we analyzed infected cells for changes in ADP-ribosylation patterns utilizing antibodies specific for ADPr. We focused on cells infected with a murine CoV, mouse hepatitis virus (MHV). If the macrodomain was indeed removing the ADPr from the N protein, we would expect to see increased N protein ADP-ribosylation in cells infected with mutant virus compared to wild-type infected cells. To determine if N protein expressed in the absence of CoV infection could be ADP-ribosylated in cell culture, we transduced Vero cells with VEEV replicon particles (VRPs) encoding the MERS-CoV N protein or control GFP at different MOIs . cache = ./cache/cord-268416-8hw80qx8.txt txt = ./txt/cord-268416-8hw80qx8.txt === reduce.pl bib === id = cord-279106-3ffa9djf author = Syatila Ab Ghani, Nur title = Side chain similarity comparisons for integrated drug repositioning and potential toxicity assessments in epidemic response scenarios: the case for COVID-19 date = 2020-10-21 pages = extension = .txt mime = text/plain words = 6970 sentences = 404 flesch = 52 summary = In this work, the three-dimensional arrangements of amino acid side chains in known drug binding sites (substructures) were used to search for similarly arranged sites in SARS-CoV-2 protein structures in the Protein Data Bank for the potential repositioning of approved compounds. The investigations of binding properties in disease-related proteins derived from the comparison of amino acid substructure arrangements allows for effective mechanism driven decision making to rank and select only the compounds with the highest potential for success and safety to be prioritized for clinical trials or treatments. In the case of the COVID-19 pandemic caused by the SARS-CoV-2 virus, we demonstrate that the pipeline can identify candidate compounds quickly and sustainably in combination with associated risk factors derived from the analysis of potential off-target site binding by the compounds to be repurposed. 33 In this work, amino acid side chain similarity searching was utilized to propose alternative target sites in 34 SARS-CoV-2 protein structures for drug repositioning. cache = ./cache/cord-279106-3ffa9djf.txt txt = ./txt/cord-279106-3ffa9djf.txt === reduce.pl bib === id = cord-266444-rw94yls8 author = Dominguez Andres, Ana title = SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date = 2020-08-19 pages = extension = .txt mime = text/plain words = 5639 sentences = 305 flesch = 44 summary = The interactome and proteome studies identified cellular processes affected by SARS-CoV-2 infection or specific viral proteins, notably innate immune signaling (19, 20, 23, (28) (29) (30) , ubiquitin ligase activities (19, 20, 23, (28) (29) (30) , p38 mitogenactivated protein kinase (MAPK) signaling (19, 20, 23, (28) (29) (30) . To assess if there were notable differences in the intensity of the changes in protein abundance in response to proteasome inhibition, we calculated relative changes in protein abundance between control and ORF9c-expressing cells from both the DMSO and MG132 conditions for proteins associated with IFN signaling or the ubiquitin proteasome (UBP) system and antigen presentation (Fig. 2D ). In contrast to the proteomic results that revealed predominant downregulation of proteins following ORF9c expression, RNA-seq analysis showed a similar number of transcripts were increased or decreased in the presence or absence of MG132 (Fig. 3A, table S2 ). cache = ./cache/cord-266444-rw94yls8.txt txt = ./txt/cord-266444-rw94yls8.txt === reduce.pl bib === id = cord-022888-dnsdg04n author = nan title = Poster Sessions date = 2009-08-19 pages = extension = .txt mime = text/plain words = 188640 sentences = 9313 flesch = 45 summary = Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. cache = ./cache/cord-022888-dnsdg04n.txt txt = ./txt/cord-022888-dnsdg04n.txt === reduce.pl bib === id = cord-268239-neb6xxlf author = Illiano, Anna title = Protein Glycosylation Investigated by Mass Spectrometry: An Overview date = 2020-08-28 pages = extension = .txt mime = text/plain words = 9540 sentences = 442 flesch = 34 summary = For example, the alanine-proline-rich antigen (Apa) glycoprotein, expressed on the cell surface of different Mycobacteria species, induced glycan-specific T-cell response, whereas the non-glycosylated form of the same protein in Escherichia coli showed reduced stimulation of the CD4 + T-cell system compared to the native antigen, giving evidence of the crucial involvement of glycosylation in T-cell activation by Apa during infection [42] . Technological breakthroughs in mass spectrometric analysis for specific glycan epitopes provide a more molecular approach to examine potential changes in glycosylation or to display a sufficient degree of alteration in glycosylation, as mixtures of commonly occurring glycosylation patterns associated with normal cells or tumor-associated signals [82, 84] . cache = ./cache/cord-268239-neb6xxlf.txt txt = ./txt/cord-268239-neb6xxlf.txt === reduce.pl bib === id = cord-265887-g5zhoyo9 author = Mukherjee, Shruti title = Host-membrane interacting interface of the SARS coronavirus envelope protein: Immense functional potential of C-terminal domain date = 2020-08-11 pages = extension = .txt mime = text/plain words = 9085 sentences = 538 flesch = 41 summary = (56) Apart from these highly conserved sequences throughout the genus, there are distinct potent glycosylation sites along the stretch that can serve as chaperone interacting motifs to help in the protein folding and/or aid in J o u r n a l P r e -p r o o f Journal Pre-proof trafficking along with the cellular machinery.(57) Glycosylation of particular asparagine residues (Asn 45, Asn 48, Asn 64, and Asn 68) in the SARS-CoV has been shown to be crucial in maintaining the proteinoligomerization events associated with the host membranes. (41) The formation of a disulfide bond may also play a crucial role in the oligomerization of the E protein, forming stable dimers, trimers, and pentamers depending on its functional requirement.(105) Thus even though the TMD spans the lipid bilayer, the CxxC motif could serve as an essential key to defining the membrane-associated oligomerization events-providing newer targets for preemptive therapeutic intervention. cache = ./cache/cord-265887-g5zhoyo9.txt txt = ./txt/cord-265887-g5zhoyo9.txt === reduce.pl bib === id = cord-279432-aik5bo6o author = Digard, Paul title = Complex formation between influenza virus polymerase proteins expressed in Xenopus oocytes date = 1989-07-31 pages = extension = .txt mime = text/plain words = 4847 sentences = 225 flesch = 50 summary = As seen in virus-infected cells, all three P proteins associated into an immunoprecipitable complex, suggesting that the system has considerable promise for the reconstruction of an active influenza RNA polymerase. In view of the fact that the P proteins must interact with RNA, it seemed possible that the high sedimentation values obtained for individually expressed PBl and PB2 (Fig. 4) and for complexes containing PBl and PB2 could have arisen from the polypeptides binding to RNA present in the lysate. Furthermore, RNase treatment of lysates containing individually expressed PB2 also failed to affect its sedimentation pattern (not shown), suggesting that the heterogeneous size distribution of the P protein complexes is not the result of association with RNA. Here, we have demonstrated the feasibility of producing all three influenza virus polymerase proteins for functional studies by the translation of in vitro transcribed mRNA analogs in Xenopus oocytes. The three influenza virus polymerase (P) proteins not associated with viral nucleocapsids in the infected cell are in the form of a complex cache = ./cache/cord-279432-aik5bo6o.txt txt = ./txt/cord-279432-aik5bo6o.txt === reduce.pl bib === id = cord-275124-7l53bvp1 author = Yao, Minghui title = A potential treatment for COVID-19 based on modal characteristics and dynamic responses analysis of 2019-nCoV date = 2020-10-21 pages = extension = .txt mime = text/plain words = 2489 sentences = 170 flesch = 64 summary = The finite element analysis (FEA) is used to study the modal characteristics of the tuned 2019-nCoV model and mistuned 2019-nCoV model in blood, respectively. Because of the relatively heavy mass of the sphere body compared to spike proteins, its modes are rigid body motion, which the sphere of COVID-19 model is fixed in modal analysis. Based on the first-order bending vibration form, the lumped mechanical model is established as illustrated in Fig. 5 . The harmonic response is conducted after the modal analysis of the mistuned 2019-nCoV model, and acceleration excitation is set as 1 mm/s 2 , as shown in Fig. 6 . (1) The frequencies of the tuned 2019-nCoV model are very close to each other, and they are all first-order bending vibrations. The frequencies of the realistic mistuned 2019-nCoV model are a range of frequencies close to each other, and every frequency corresponds to the first-order bending vibration of one spike protein. cache = ./cache/cord-275124-7l53bvp1.txt txt = ./txt/cord-275124-7l53bvp1.txt === reduce.pl bib === id = cord-266977-5swwc6kr author = Secker, Thomas.J. title = Journal of Hospital Infection A cold water, ultrasonic activated stream efficiently removes proteins and prion-associated amyloid from surgical stainless steel date = 2020-09-19 pages = extension = .txt mime = text/plain words = 4562 sentences = 241 flesch = 44 summary = authors: Secker, Thomas.J.; Leighton, Timothy.G.; Offin, Douglas.G.; Birkin, Peter.R.; Hervé, Rodolphe.C.; Keevil, Charles.W. title: Journal of Hospital Infection A cold water, ultrasonic activated stream efficiently removes proteins and prion-associated amyloid from surgical stainless steel Aim: To test the efficacy of an ultrasonically activated stream for the removal of tissue 27 proteins, including prion-associated amyloid, from surgical stainless steel (SS) surfaces. This study has tested the efficacy of UAS technology for the removal of 239 total protein and prion-amyloid from stainless steel, which is considered the most difficult 240 contaminant to decontaminate in the surgical field. 335 J o u r n a l P r e -p r o o f Tissue protein (Dark grey bars) and prion-associated amyloid (light grey bars) attachment 545 from different prion-infected brain homogenates (22L, ME7 and 263K) to surgical stainless 546 steel pre and post treatment with an ultrasonically activated stream (UAS) (Graph A). cache = ./cache/cord-266977-5swwc6kr.txt txt = ./txt/cord-266977-5swwc6kr.txt === reduce.pl bib === id = cord-279463-bli8hwda author = Lipp, Joachim title = The membrane-spanning segment of invariant chain (Iγ) contains a potentially cleavable signal sequence date = 1986-09-26 pages = extension = .txt mime = text/plain words = 6276 sentences = 367 flesch = 62 summary = As type II membrane proteins contain only a single stretch of hydrophobic amino acid residues, this might function as a signal for membrane insertion as well as a membrane anchor (Markoff et al., 1984; Spiess and Lodish, 1986) . plycat is an in-frame fusion between the 5' region of ly encoding the cytoplas, mic, membrane-spanning segment plus 12 amino acids of the exoplasmic portion of ly and the gene encoding the cytoplasmic protein chloramphenicol acetyltransferase (CAT). After protease digestion in the presence of microsomal membranes, lyCAT* is reduced in molecular weight by about 2 kd, suggesting that it exposes 20-30 amino acid residues on the cytoplasmic side ( Figure 3 , lanes 2 and 3). This signal sequence is located in the amino-terminal half of the membrane-spanning segment, and it is cleaved when the preceding cytoplasmic domain is removed. cache = ./cache/cord-279463-bli8hwda.txt txt = ./txt/cord-279463-bli8hwda.txt === reduce.pl bib === id = cord-272260-88l9bq4i author = Han, L.Y. title = Prediction of functional class of novel viral proteins by a statistical learning method irrespective of sequence similarity date = 2005-01-05 pages = extension = .txt mime = text/plain words = 4116 sentences = 220 flesch = 47 summary = The web-based software SVMProt (http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi) to some extent assigns protein functional family irrespective of sequence similarity and has been found to be useful for studying distantly related proteins [Cai, C.Z., Han, L.Y., Ji, Z.L., Chen, X., Chen, Y.Z., 2003. This suggests that SVMProt to some extent is capable of functional class assignment irrespective of sequence similarity and it is potentially useful for facilitating functional study of novel viral proteins. These include evolutionary analysis (Benner et al., 2000; Eisen, 1998) , hidden Markov models (Fujiwara and Asogawa, 2002) , structural consideration (Di Gennaro et al., 2001; Teichmann et al., 2001) , protein/gene fusion (Enright et al., 1999; Marcotte et al., 1999) , proteinprotein interactions (Bock and Gough, 2001) , motifs (Hodges and Tsai, 2002) , family classification by sequence clustering (Enright et al., 2002) , and functional family prediction by statistical learning methods (Cai et al., 2003 Han et al., 2004; Jensen et al., 2002; Karchin et al., 2002) . cache = ./cache/cord-272260-88l9bq4i.txt txt = ./txt/cord-272260-88l9bq4i.txt === reduce.pl bib === id = cord-272241-2fwz8z8n author = Kumar, Amit title = Exploring the SARS-CoV-2 structural proteins for multi-epitope vaccine development: an in-silico approach date = 2020-09-09 pages = extension = .txt mime = text/plain words = 4608 sentences = 281 flesch = 49 summary = title: Exploring the SARS-CoV-2 structural proteins for multi-epitope vaccine development: an in-silico approach Hence, in this study, we have used immunoinformatic approaches to predict highly antigenic epitopes from SARS-CoV-2 structural proteins that would evoke a strong immune response in humans. For this purpose, we have used the structural proteins: Spike, Envelope, and nucleocapsid to predict B-cell, cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes for construction of vaccine. We have also performed the docking and molecular dynamic simulations (MDS) between the vaccine and human Toll-like Receptor-3 (TLR-3) to study their binding stability. The VaxiJen 2.0 server predicts the antigenicity of the multi-epitope vaccine peptide based on the physicochemical properties of the input protein. Whereas, ANTIGENpro server predicts the antigenicity of the multi-epitopic vaccine based on the protein microarray data analysis of the target organism. Three structural proteins (spike glycoprotein, nucleocapsid, and envelope) were selected to construct a multi-epitope vaccine, which is capable of eliciting the humoral and cell-mediated immune response. cache = ./cache/cord-272241-2fwz8z8n.txt txt = ./txt/cord-272241-2fwz8z8n.txt === reduce.pl bib === id = cord-271693-7tg21up3 author = Zheng, Fan title = Identifying persistent structures in multiscale ‘omics data date = 2020-10-03 pages = extension = .txt mime = text/plain words = 4889 sentences = 291 flesch = 48 summary = Many different approaches have been devised or applied to detect structures in biological data, including standard clustering, network community detection, and low-dimensional data projection [5] [6] [7] , some of which can be tuned for sensitivity to objects of a certain size or scale (so-called 'resolution parameters') [8, 9] . We first explored the idea of measuring community persistence via analysis of synthetic datasets [15] in which communities were simulated and embedded in the similarity network at two different scales (Supplementary Fig. 1a; Methods) . Application to protein-protein interaction networks from budding yeast and human found that HiDeF captured knowledge in GO more significantly than previous pipelines proposed for this task, including the NeXO approach to hierarchical community detection [23] and standard hierarchical clustering of pairwise protein distances calculated by three recent network embedding approaches [24] [25] [26] (Fig. 3a, Fig. 7) . cache = ./cache/cord-271693-7tg21up3.txt txt = ./txt/cord-271693-7tg21up3.txt === reduce.pl bib === id = cord-276988-bvsz5q6d author = Neu, Carolin T. title = Post-Transcriptional Expression Control in Platelet Biogenesis and Function date = 2020-10-15 pages = extension = .txt mime = text/plain words = 11394 sentences = 581 flesch = 38 summary = Additionally, we will focus on the currently known concepts of post-transcriptional control mechanisms important for RNA fate within platelets with a special emphasis on RBPs. Blood platelets-the major players in hemostasis-are small anucleate cell fragments with a characteristic discoid shape and a diameter of 1 to 3 µm that originate from megakaryocytes (MKs). The m 7 G cap and poly(A) tail promote mRNA translation and stability, while the UTRs expose sequences for RNA-binding proteins (RBPs) and regulatory sites for microRNA (miRNA)-mediated translational and degradation control [45, [52] [53] [54] . Moreover, RNA-Seq analysis of platelet miRNAs in patients with myocardial infarction revealed nine differentially expressed platelet miRNAs compared to healthy controls, which were released upon platelet aggregation and taken up by endothelial cells via a vesicle-dependent mechanism [80] . Megakaryopoiesis, megakaryocyte maturation, as well as platelet formation, were shown to be highly complex processes that are regulated on multiple levels including epigenetic, transcriptional as well as post-transcriptional gene expression control mechanisms. cache = ./cache/cord-276988-bvsz5q6d.txt txt = ./txt/cord-276988-bvsz5q6d.txt === reduce.pl bib === id = cord-277293-eo3bei9x author = Fondong, Vincent N. title = Geminivirus protein structure and function date = 2013-04-25 pages = extension = .txt mime = text/plain words = 10141 sentences = 507 flesch = 47 summary = The replication-associated protein (Rep) encoded by the AC1 ORF (also called AL1) in bipartite geminiviruses and by C1 (also called L1) in monopartite geminiviruses (except mastreviruses) is conserved in sequence, position and function (Hanley-Bowdoin et al., 2004) and is expressed under the control of a bidirectional core promoter in the IR (Hanley-Bowdoin et al., 1999) . SINAC1 levels were shown to be higher in ToLCV-infected cells, suggesting that NAC1 is involved in viral DNA replication (Selth et al., 2005) , possibly through an interaction with REn. Recently, the Tomato leaf curl Kerala virus REn was shown to interact with Rep and enhance the Repmediated ATPase activity (Pasumarthy et al., 2010) , thus confirming a role for REn in viral DNA replication. cache = ./cache/cord-277293-eo3bei9x.txt txt = ./txt/cord-277293-eo3bei9x.txt === reduce.pl bib === id = cord-279598-xzionafe author = Chang, Chia-Yu title = Identification of Neutralizing Monoclonal Antibodies Targeting Novel Conformational Epitopes of the Porcine Epidemic Diarrhoea Virus Spike Protein date = 2019-02-21 pages = extension = .txt mime = text/plain words = 5378 sentences = 267 flesch = 53 summary = title: Identification of Neutralizing Monoclonal Antibodies Targeting Novel Conformational Epitopes of the Porcine Epidemic Diarrhoea Virus Spike Protein However, E10E-1-10, which targets a novel neutralizing epitope as shown with ICC staining, was also capable of binding to the full-length PEDV spike protein as well as truncated PEDV proteins, S 1-639 , S 1-575 , S 1-509 , S 1-501 , and S 1-485 with appropriate dilution effects. Similar to the results obtained by ICC staining, E10E-1-10 showed no binding ability www.nature.com/scientificreports www.nature.com/scientificreports/ toward PEDV S 1-435 by ELISA and therefore, an NmAb targeting a novel epitope of the new variant of PEDV specifically at a.a. 435-485 in the S1 region was confirmed. To further determine whether the binding of neutralizing epitopes require conformational integrity, immunodot blotting was performed by denaturing the various truncated PEDV spike proteins. Cell Attachment Domains of the Porcine Epidemic Diarrhea Virus Spike Protein Are Key Targets of Neutralizing Antibodies cache = ./cache/cord-279598-xzionafe.txt txt = ./txt/cord-279598-xzionafe.txt === reduce.pl bib === id = cord-274424-juj71nc5 author = Pulford, David J. title = Intracellular processing of the porcine coronavirus transmissible gastroenteritis virus spike protein expressed by recombinant vaccinia virus date = 1991-06-30 pages = extension = .txt mime = text/plain words = 4901 sentences = 231 flesch = 49 summary = Abstract The Spike (S) protein from a virulent British field isolate of porcine transmissible gastroenteritis virus (TGEV) FS772/70 was constructed from cDNA and inserted into the vaccinia virus (VV) thymidine kinase gene locus under the control of the VV early/late gene P7.5K promoter. In this paper we report the construction of a FS772/ 70 cDNA S gene and its expression by a recombinant vaccina virus (rVV) to study the antigenicity and cellular localization of the S protein. Expression of the recombinant spike antigens TGEV gene products synthesized by vTS-1 and vTSA-1 were analyzed by pulse labeling rVV-infected HTK-cells with L-[35S]methionine in the presence or absence of 10 pg ml-' tunicamycin for 6 hr. The lack of detectable ~160 or ~130 in the culture medium of vTS-l-and vTSA-l-infected cells, respectively (Fig. 4 lanes 4 and 7) , could result from the levels being too low to be detected by the antibodies due to reduction in synthesis or the lack of glycosylation of the S protein in the presence of tunicamycin. cache = ./cache/cord-274424-juj71nc5.txt txt = ./txt/cord-274424-juj71nc5.txt === reduce.pl bib === id = cord-279629-t1xjy12y author = Nazneen Akhand, Mst Rubaiat title = Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine date = 2020-04-15 pages = extension = .txt mime = text/plain words = 6717 sentences = 379 flesch = 47 summary = The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Hence, the study was designed to develop a chimeric recombinant vaccine against COVID-19 by targeting four major structural proteins of the pathogen, while revealing the evolutionary history of different species of coronavirus based on whole genome and protein domain-based phylogeny. Apart from the human coronaviruses, we introduced other coronaviruses which choose different species of bats, whale, turkey, rat, mink, ferret, swine, camel, rabbit, cow and others as host (Supplementary TableDomain analysis of spike protein of coronaviruses reveals that they contain mainly one signature domains namely, coronavirus S2 glycoprotein (IPR002552), which is present in all the candidates. Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in silico approach. cache = ./cache/cord-279629-t1xjy12y.txt txt = ./txt/cord-279629-t1xjy12y.txt === reduce.pl bib === id = cord-270514-36k9xo7f author = van der Woude, Roosmarijn title = Drivers of recombinant soluble influenza A virus hemagglutinin and neuraminidase expression in mammalian cells date = 2020-08-14 pages = extension = .txt mime = text/plain words = 3966 sentences = 249 flesch = 49 summary = Recombinant soluble trimeric influenza A virus hemagglutinins (HA) and tetrameric neuraminidases (NAs) have proven to be excellent tools to decipher biological properties. The two surface envelope proteins of IAV have opposing functions; the trimeric hemagglutinin (HA) binds to sialic acid containing glycans to enable the virus to enter cells, 1,2 the tetrameric neuraminidase (NA) cleaves sialic acids to release new viral particles from the membrane. However, we observed a significant increase in expression yields and determined that it reduced the use of expensive antibodies and provided an excellent handle, as well as an internal read out, of a glycan binding protein. The N-terminal sfGFP increases yields, maintains biological activity, structure and antigenicity, and aids protein quantitation during expression and purification. To determine that sfGFP-NA fusions are enzymatically, antigenically and structurally similar to their non-fused counterparts, we analyzed the GCN4, TB, and sfGFP-TB-N2 proteins with MUNANA and NA specific antibodies (Figure 3 ). cache = ./cache/cord-270514-36k9xo7f.txt txt = ./txt/cord-270514-36k9xo7f.txt === reduce.pl bib === id = cord-281005-6gi18vka author = Singh, Praveen Kumar title = Mutations in SARS-CoV-2 Leading to Antigenic Variations in Spike Protein: A Challenge in Vaccine Development date = 2020-09-01 pages = extension = .txt mime = text/plain words = 3161 sentences = 203 flesch = 57 summary = title: Mutations in SARS-CoV-2 Leading to Antigenic Variations in Spike Protein: A Challenge in Vaccine Development Therefore, we aimed to predict the mutations in the spike protein (S) of the SARS-CoV-2 genomes available worldwide and analyze its impact on the antigenicity. A total of 1,604 spike proteins were extracted from 1,325 complete genome and 279 partial spike coding sequences of SARS-CoV-2 available in NCBI till May 1, 2020 and subjected to multiple sequence alignment to find the mutations corresponding to the reported single nucleotide polymorphisms (SNPs) in the genomic study. In this study, we aimed to predict the mutations in the spike protein (S) of SARS-CoV-2 genomes available in the database (whole genome sequences as well as partial coding sequences of spike protein) and analyze the effect of each mutation on the antigenicity of the predicted epitopes. cache = ./cache/cord-281005-6gi18vka.txt txt = ./txt/cord-281005-6gi18vka.txt === reduce.pl bib === id = cord-282604-xp71rkxc author = Nikolaev, EN title = Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein date = 2020-05-25 pages = extension = .txt mime = text/plain words = 2181 sentences = 114 flesch = 53 summary = title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein We have developed a mass-spectrometry based method for the detection of the SARS CoV-2 virus in nasopharynx epithelial swabs, based on the detection of the viral nucleocapsid N protein. The N protein of the SARS-COV-2 virus, the most abundant protein in the virion, is the best candidate for mass-spectrometric detection of the infection, and MS-based detection of several peptides from the SARS-COoV-2 nucleoprotein has been reported earlier by the Sinz group [4]. We have performed a pilot study on nasopharynx epithelial swabs already collected from patients with CODIV-19 for RT-qPCR and showed confident identification of the N protein of the SARS CoV-2 virus by mass-spectrometry with the use of a very basic sample preparation procedure. Mass Spectrometric Identification of SARS-CoV-2 Proteins from Gargle Solution Samples of COVID-19 Patients cache = ./cache/cord-282604-xp71rkxc.txt txt = ./txt/cord-282604-xp71rkxc.txt === reduce.pl bib === id = cord-271091-ffn59sgf author = Galao, Rui P title = Saccharomyces cerevisiae: a versatile eukaryotic system in virology date = 2007-10-10 pages = extension = .txt mime = text/plain words = 6539 sentences = 318 flesch = 42 summary = These include the analysis of the function of individual proteins from important pathogenic viruses, the elucidation of key processes in viral replication through the development of systems that allow the replication of higher eukayotic viruses in yeast, and the use of yeast in antiviral drug development and vaccine production. Although the expression of viral proteins in yeast not always necessarily reflects their role in higher eukaryotes, here we selected some examples in which the analysis in yeast of their effect on highly conserved cellular processes such as cell cycle control, apoptosis or mRNA degradation have contributed to the current understanding of the pathogenesis of important viral pathogens such as HIV-1 and HCV. The identification of the host factors involved in viral RNA replication is a priority area of research in virology because it can provide new targets for antiviral drug development. cache = ./cache/cord-271091-ffn59sgf.txt txt = ./txt/cord-271091-ffn59sgf.txt === reduce.pl bib === id = cord-280679-jj3wzojy author = Marblestone, Jeffrey G. title = Comparison of SUMO fusion technology with traditional gene fusion systems: Enhanced expression and solubility with SUMO date = 2006-01-01 pages = extension = .txt mime = text/plain words = 4854 sentences = 250 flesch = 54 summary = For this study, three model proteins, enhanced green florescent protein (eGFP), matrix metalloprotease-13 (MMP13), and myostatin (growth differentiating factor-8, GDF8), were fused to the C termini of maltose-binding protein (MBP), glutathione S-transferase (GST), thioredoxin (TRX), NUS A, ubiquitin (Ub), and SUMO tags. Taken together, these results demonstrate that SUMO is superior to commonly used fusion tags in enhancing expression and solubility with the distinction of generating recombinant protein with native sequences. Three candidate proteins, enhanced green fluorescent protein (eGFP), and two previously described difficult-to-express proteins, matrix metalloprotease-13 (MMP13) and myostatin (growth differentiating factor-8, GDF8), were expressed as fusions with maltose-binding protein (MBP), glutathione S-transferase (GST), thioredoxin (TRX), NUS A, ubiquitin (Ub), and SUMO. The ability of commonly used fusion tags to enhance protein expression and solubility was investigated using three candidate proteins (eGFP, MMP13, and GDF8) and six fusion tags (SUMO, Ub, MBP, GST, TRX, and NUS A). cache = ./cache/cord-280679-jj3wzojy.txt txt = ./txt/cord-280679-jj3wzojy.txt === reduce.pl bib === id = cord-275023-0z219rcy author = Cerofolini, Linda title = Orientation of immobilized antigens on common surfaces by a simple computational model: Exposition of SARS-CoV-2 Spike protein RBD epitopes date = 2020-07-29 pages = extension = .txt mime = text/plain words = 3485 sentences = 198 flesch = 44 summary = title: Orientation of immobilized antigens on common surfaces by a simple computational model: Exposition of SARS-CoV-2 Spike protein RBD epitopes In this manuscript, we apply a simple computational model, based on united-residue modelling, to the prediction of the orientation of the receptor binding domain of the SARS-CoV-2 spike protein on surfaces commonly used in lateral-flow devices. In this manuscript we apply a very simple method based on a unitedresidue modelling of protein-surface interactions, to specifically address the problem of determining the orientation of the SARS-CoV-2 Spike protein Receptor Binding Domain (RBD) on a few prototypical surfaces for biomedical use. In this work, we describe the use of united-residue modelling for the prediction of the orientation of the receptor binding domain of the spike protein of the novel coronavirus SARS-CoV-2, a protein of high immunological relevance at the most commonly used surfaces for the preparation of lateral-flow immunochemical devices. cache = ./cache/cord-275023-0z219rcy.txt txt = ./txt/cord-275023-0z219rcy.txt === reduce.pl bib === id = cord-274293-kzmch37j author = Yang, Li title = Tandem mass tag-based quantitative proteomic analysis of lycorine treatment in highly pathogenic avian influenza H5N1 virus infection date = 2019-10-02 pages = extension = .txt mime = text/plain words = 6734 sentences = 347 flesch = 46 summary = Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Therefore, we performed a comparative proteomic analysis to determine the effects of lycorine at the protein level in GD178-infected MDCK cells to understand its mode of action. The functional classification of DEPs was conducted by KEGG enrichment analysis, and each protein was assigned to at least one of the following pathways: human T-lymphotropic virus-1 infection pathway (path: ko05166), cell adhesion molecules (CAMs) (path: ko04514), epidermal growth factor receptor tyrosine kinase inhibitor resistance (path: ko01521), Janus kinase-STAT signaling pathway (path: ko04630), and pancreatic cancer (path: ko05212) (Fig. 3C) . As a result, AIV infection may induce Nup93 to complete the viral cycle, and the process of protein targeting into Nup93 after lycorine treatment may partly be explained by the blockage of vRNPs in the host cellular nucleus. Functional proteomic studies of lycorine-treated MDCK cells on highly pathogenic avian influenza H5N1 virus infection cache = ./cache/cord-274293-kzmch37j.txt txt = ./txt/cord-274293-kzmch37j.txt === reduce.pl bib === id = cord-281124-4nhy35xn author = Soowannayan, Chumporn title = RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp date = 2011-08-03 pages = extension = .txt mime = text/plain words = 5596 sentences = 259 flesch = 53 summary = To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. In a preliminary attempt to identify an RNA packaging signal in the GAV genome, EMSAs were performed using ssRNAs synthesized to various genome regions including (i) an ORF1b gene 39-region spanning the relative position to the genome packaging signal identified in MHV [28] , (ii) a 39-terminal genome region corresponding in position to the region in the infectious bronchitis virus (IBV) genome reported to contain an RNA binding domain [29] and (iii) the 59-genomic RNA terminus which, in coronaviruses, has also been reported to interact specifically with N protein [30] . cache = ./cache/cord-281124-4nhy35xn.txt txt = ./txt/cord-281124-4nhy35xn.txt === reduce.pl bib === id = cord-283035-tpqf458q author = Thanthrige-Don, Niroshan title = Analyses of the spleen proteome of chickens infected with Marek's disease virus date = 2009-08-01 pages = extension = .txt mime = text/plain words = 7902 sentences = 373 flesch = 46 summary = In total, 61 protein spots representing 48 host proteins were detected as either quantitatively (false discovery rate (FDR) ≤ 0.05 and fold change ≥ 2) or qualitatively differentially expressed at least once during different sampling points. A representative gel image showing 2D gel electrophoresis map of the relative locations of spots that displayed significant quantitative differential expression (FDR ≤ 0.05 and fold change ≥ 2) at least once during different sampling times. Comparison of total numbers of significantly differentially expressed protein spots in MDV-infected spleens at various sampling time points. Venn diagram summarizing the spots that were significantly differentially expressed in the spleen tissues of MDV-infected chickens according to their corresponding time of sampling. In the present study, we have profiled the global protein expression changes in the chicken spleen in response to MDV infection at various time points representing the different phases of MDV life cycle. Proteomics analysis of differential expression of cellular proteins in response to avian H9N2 virus infection in human cells cache = ./cache/cord-283035-tpqf458q.txt txt = ./txt/cord-283035-tpqf458q.txt === reduce.pl bib === id = cord-280360-rh37d5wc author = Gibson, David S. title = Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis – Proteomic patterns of joint inflammation in early stage disease date = 2009-05-02 pages = extension = .txt mime = text/plain words = 8297 sentences = 388 flesch = 41 summary = title: Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis – Proteomic patterns of joint inflammation in early stage disease Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis -Proteomic patterns of joint inflammation in early stage disease 1 We initially performed a study of the proteins expressed within synovial fluid and plasma in early JIA in order to discover novel biomarkers which distinguish between local and systemic components of joint inflammation in arthritis. The simultaneous analysis of individual paired plasma and synovial fluids from ten patients ( Table 1 , study group A) was used to initially isolate joint-specific protein expression profiles, without introducing bias from inter-individual differences. A number of proteins with consistent synovial and plasma 'specific' expression patterns are highlighted and quantified to demonstrate the ability to reliably differentiate molecular fingerprints of local and systemic disease across patient groups by this gel based approach. cache = ./cache/cord-280360-rh37d5wc.txt txt = ./txt/cord-280360-rh37d5wc.txt === reduce.pl bib === id = cord-280429-4fota9rl author = Medvedev, Kirill E. title = Functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold date = 2018-06-13 pages = extension = .txt mime = text/plain words = 7468 sentences = 465 flesch = 49 summary = 10 However, structural analyses of virion architecture and coat protein topology have revealed unexpected similarities, not visible in sequence comparisons, suggesting a common origin for viruses that infect hosts residing in different domains of life. In this current work, we provide functional and evolutionary analysis of viral proteins containing a Rossmann-like fold that can be found in the Evolutionary Classification of protein Domains (ECOD) database developed in our lab. The structures represented gene products from 21 viral taxonomical families with host ranges from all kingdoms of life (http://prodata.swmed.edu/rossmann_fold/viruses/). Our analysis detected 14 different bacterial virus structure topology types defined by ECOD T-groups that contain a Rossmann-like fold (Fig. 2, 12 topology groups shown). Like the bacterial and eukaryotic branches in the tree of life, the Archea are host to a multitude of Functional and Evolutionary Analysis of Viral Proteins viruses. 61 Among viral protein structures containing the minimal Rossmann fold, 14 protein families are known helicases (http://prodata.swmed.edu/ross-mann_fold/viruses/). cache = ./cache/cord-280429-4fota9rl.txt txt = ./txt/cord-280429-4fota9rl.txt === reduce.pl bib === id = cord-277424-9aimvogs author = Criscitiello, Michael F. title = Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity date = 2019-11-13 pages = extension = .txt mime = text/plain words = 12782 sentences = 699 flesch = 42 summary = In serum, 103 deiminated proteins were overall identified, including key immune and metabolic mediators including complement components, immunoglobulin-based nanobodies, adiponectin and heat shock proteins. Further deiminated proteins identified in llama serum and serumderived EVs by F95 enrichment and LCeMS/MS analysis included key proteins of camelid innate and adaptive immunity, nuclear proteins, as well as proteins involved in metabolic function. Deimination protein candidates identified here in llama serum and EVs, which are involved in immune, nuclear and metabolic functions, are further discussed below, including where appropriate in a comparative context with relevant human diseases. As a structurally analogous immunoglobulin in shark, new antigen receptor (NAR) (Greenberg et al., 1995; Barelle et al., 2009; Flajnik and Dooley, 2009; De Silva et al., 2019) was recently also found to be deiminated (Criscitiello et al., 2019) , our current finding may provide novel insights into function of these immune proteins and be useful for refinement in therapeutic nanobody development. cache = ./cache/cord-277424-9aimvogs.txt txt = ./txt/cord-277424-9aimvogs.txt === reduce.pl bib === id = cord-272268-8vrcwwll author = Kedersha, Nancy title = Chapter 4 Regulation of Translation by Stress Granules and Processing Bodies date = 2009-10-27 pages = extension = .txt mime = text/plain words = 8598 sentences = 456 flesch = 45 summary = Cytoplasmic stress granules (SGs) and processing bodies (PBs) are dynamic structures that form in response to stress-induced translational arrest. Critical components of the ''cell biology'' of protein translation are mRNP granules known as processing bodies (PBs) and stress granules (SGs). These transient cytoplasmic ''structures'' are actively assembled from untranslated mRNA by a host of RNA-binding proteins, which determine whether specific transcripts will be reinitiated, degraded, or stored. In 1999, it was noted that stress-induced translational arrest causes untranslated mRNPs to assemble into large cytoplasmic ''SGs,'' whose formation is triggered by, and dependent upon, the phosphorylation of eIF2a. Virus infection also induces the assembly of SGs and PBs suggesting that RNA granules play a role in reprogramming mRNA translation/decay during viral infection. RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2a to the assembly of mammalian stress granules cache = ./cache/cord-272268-8vrcwwll.txt txt = ./txt/cord-272268-8vrcwwll.txt === reduce.pl bib === id = cord-279586-likfvwwj author = Jin, Jian title = Effects of Sonication on the In vitro Digestibility and Structural Properties of Buckwheat Protein Isolates date = 2020-09-17 pages = extension = .txt mime = text/plain words = 4831 sentences = 248 flesch = 48 summary = The present work investigated the effects of sonication at different amplitudes and durations on the in vitro digestibility of buckwheat protein isolates (BPIs). The tertiary structure analysis showed that sonication exposed the hydrophobic core buried inside the protein molecules and broke the intramolecular crosslinks, based on the increase in the surface hydrophobicity and intrinsic fluorescence and the decrease in the disulphide content. Therefore, this study was aimed at investigating the effects of sonication duration and acoustic amplitude on the in vitro digestibility of buckwheat protein isolates (BPIs). In addition, the effects of sonication on the tertiary structures (surface hydrophobicity, intrinsic fluorescence, sulfhydryl and disulfide bond contents), secondary structure, particle size, zeta-potential and microstructure of BPIs were studied to elucidate the structural mechanism underlying the effect of ultrasound on the digestibility of the proteins. cache = ./cache/cord-279586-likfvwwj.txt txt = ./txt/cord-279586-likfvwwj.txt === reduce.pl bib === id = cord-284208-8fsqgkw5 author = Zolla, Lello title = Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins date = 2008-11-07 pages = extension = .txt mime = text/plain words = 6987 sentences = 306 flesch = 35 summary = In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. cache = ./cache/cord-284208-8fsqgkw5.txt txt = ./txt/cord-284208-8fsqgkw5.txt === reduce.pl bib === id = cord-279691-v5kpmk0b author = Hagemeijer, Marne C. title = Biogenesis and Dynamics of the Coronavirus Replicative Structures date = 2012-11-21 pages = extension = .txt mime = text/plain words = 9036 sentences = 483 flesch = 43 summary = Upon infection, coronaviruses extensively rearrange cellular membranes into organelle-like replicative structures that consist of double-membrane vesicles and convoluted membranes to which the nonstructural proteins involved in RNA synthesis localize. This review will summarize the current knowledge on the biogenesis of the replicative structures, the membrane anchoring of the replication-transcription complexes, and the location of viral RNA synthesis, with particular focus on the dynamics of the coronavirus replicative structures and individual replication-associated proteins. A distinctive common feature of +RNA viruses is the replication of their genomes in the cytoplasm of the host cell in association with rearranged cellular membranes that are remodeled into organelle-like membranous structures to which the viral replication-transcription complexes (RTCs) localize. The first detectable membrane rearrangements in CoV-infected cells are 200 to 350 nm organelle-like structures that have been described for both MHV [47, 62] and the SARS-CoV [5, 63] and consist of spherical vesicles containing double lipid bilayers, termed DMVs ( Figure 2 ). cache = ./cache/cord-279691-v5kpmk0b.txt txt = ./txt/cord-279691-v5kpmk0b.txt === reduce.pl bib === id = cord-281101-gv1sgbk1 author = Shin, Gu-Choul title = Preparation and characterization of a novel monoclonal antibody specific to severe acute respiratory syndrome-coronavirus nucleocapsid protein date = 2006-08-30 pages = extension = .txt mime = text/plain words = 5929 sentences = 279 flesch = 52 summary = Severe acute respiratory syndrome-coronavirus nucleocapsid (SARS-CoV N) protein has been found to be important to the processes related to viral pathogenesis, such as virus replication, interference of the cell process and modulation of host immune response; detection of the antigen has been used for the early diagnosis of infection. Reactivity of SARS-N mAbs with SARS-CoV infected cells was determined by immunofluorescence assay, performed according to the instructions of the manufacturer (Euroimmun, Germany). To further assess the specificity of the mAbs, antigen-capture ELISA was performed with human coronavirus-infected cell lysates and BrSARS-N protein as positive control (Fig. 6B) . (B) Cross-reactivity of SARS-N mAbs was examined by antigen-capture ELISA using human coronavirus OC43 lysates (256 HA unit), BrSARS-N protein (500 ng/well) and PBST buffer with 1% BSA as control. These mAbs were available for use in detecting SARS-CoV N protein by various diagnostic methods, such as immunoblot assay, immunofluorescence assay and antigen-capture ELISA (Table 3) . cache = ./cache/cord-281101-gv1sgbk1.txt txt = ./txt/cord-281101-gv1sgbk1.txt === reduce.pl bib === id = cord-286219-qcx5ehnh author = Calistri, Arianna title = The Ubiquitin-Conjugating System: Multiple Roles in Viral Replication and Infection date = 2014-05-06 pages = extension = .txt mime = text/plain words = 10182 sentences = 498 flesch = 41 summary = In this review we will present several examples of the complex interplay that links viruses and the ubiquitin conjugation machinery, with a special focus on the mechanisms evolved by the human immunodeficiency virus to escape from cellular restriction factors and to exit from infected cells. Furthermore, small DNA viruses with known oncogenic activity, such as the human papillomavirus (HPV), adenoviruses and polyomaviruses, take control of the cell cycle by usurping specific cellular Ub ligase complexes to target crucial cell cycle regulators such as p53 and the protein of the retinoblastoma (pRB) for degradation [58] . In addition to this important function, which is likely required for proper trafficking and maturation of the viral envelope glycoproteins, Vpu has been more recently characterized for yet another crucial role, connected with the ability of the virus to evade a specific IFN-1 induced antiviral factor: the B cell stromal factor 2 (BST-2) or tetherin. cache = ./cache/cord-286219-qcx5ehnh.txt txt = ./txt/cord-286219-qcx5ehnh.txt === reduce.pl bib === id = cord-285180-32bxx94u author = Lee, Sunhee title = Functional characterization and proteomic analysis of the nucleocapsid protein of porcine deltacoronavirus date = 2015-10-02 pages = extension = .txt mime = text/plain words = 7641 sentences = 359 flesch = 43 summary = Time-course Western blot analysis revealed that the PK-PDCoV-N cells stably express and accumulate robust levels of a ∼45 kDa recombinant N protein, larger than its predicted molecular weight of approximately 38 kDa possibly due to post-translational modifications and the presence of C-terminal myc and histidine tags (Fig. 1C ). To identify the differentially expressed cellular protein spots in PK-PDCoV-N cells at different time points, 10 protein spots with a statistically significant alteration, including 8 up-regulated and 2 down-regulated protein spots (Fig. 4B) , were selected and manually excised from the stained gels. These proteins showing altered expression were associated with various cellular functions including intracellular transport, metabolic processes, gene regulation, the stress response, protein synthesis, cytoskeleton networks, and cell division. Coronavirus infection of cultured cells is known to cause ER stress and to induce the UPR, which then crosstalks with various cellular signaling pathways, including mitogen-activated protein kinase cascades, autophagy, apoptosis, and innate immune responses, indicating the involvement of UPR activation in virus-host interactions and viral pathogenesis . cache = ./cache/cord-285180-32bxx94u.txt txt = ./txt/cord-285180-32bxx94u.txt === reduce.pl bib === id = cord-283096-qm7h4qui author = Jeon, Young Joo title = ISG15 and immune diseases date = 2010-02-12 pages = extension = .txt mime = text/plain words = 11144 sentences = 606 flesch = 44 summary = Some of them are type I IFN-induced proteins, such as PKR and RIG-I, and some are the key regulators that are involved in IFN signaling, such as JAK1 and STAT1, implicating the role of ISG15 and its conjugates in type I IFN-mediated innate immune responses. Viral infection also strongly induces ISG15 [18, 19] because one of its major host responses is the production of type I IFNs. A number of proteins that are involved in antiviral signaling pathways, including RIG-I, MDA-5, Mx1, PKR, STAT1, and JAK1, have been identified as target proteins for ISGylation. Swiss 3T3 cells expressing constitutively active MKK7-JNK1β fusion protein show increased resistance to apoptosis induced by vesicular stomatitis virus (VSV) infection, suggesting the involvement of JNK signaling pathway in antiviral response. acid seems to elevate the levels of ISG15 and its conjugates by stimulating cells to secrete IFNs. UBE1L is a 112-kDa protein that shows a 45% identity in amino acid sequence to the human ubiquitin-activating E1 enzyme (UBE1) [73] . cache = ./cache/cord-283096-qm7h4qui.txt txt = ./txt/cord-283096-qm7h4qui.txt === reduce.pl bib === id = cord-286635-7aflpgxd author = YANG, Yong-xin title = Comparative Proteomic Analysis of Plasma from Clinical Healthy Cows and Mastitic Cows date = 2009-10-31 pages = extension = .txt mime = text/plain words = 2471 sentences = 102 flesch = 47 summary = After staining with silver nitrate and Coomassie Blue, differential expression proteins were detected by PDQuest 7.4 software, and then subjected to ion trap mass spectrometer equipped with a Surveyor HPLC System, differential spots of protein were identified. This investigation was to detect the expressed proteins in plasma from clinical mastitic and healthy dairy cows by 2-DE providing a platform for parallel analysis, and then, to identify differential proteins by ion trap mass spectrometer equipped with HPLC System, in order to probe the pathogenesis of mastitis and find new biomarkers of mastitis-associated proteins for diagnosis and treatment. To probe protein expression pattern changes in plasma from healthy dairy cows and clinical mastitic cows, this subject analyzed and identified differential protein spots using 2-DE and ion trap mass spectrometer equipped with HPLC System. cache = ./cache/cord-286635-7aflpgxd.txt txt = ./txt/cord-286635-7aflpgxd.txt === reduce.pl bib === id = cord-281528-xy8j5jiv author = Di Paola, Luisa title = The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach date = 2020-06-17 pages = extension = .txt mime = text/plain words = 6715 sentences = 402 flesch = 56 summary = All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein. We also provided biophysical evidence based on the elastic network modeling (ENM) approach, combined with perturbation-response scanning (PRS) 36 that AMRs in both viruses acted as a mediator of intermolecular allostery between the S protein and ACE2. The map of the participation coefficient projected onto the ribbon structure of the SARS-CoV/ACE2 complex ( Figure 1C ) shows an active region (P > 0) in the junction between the fusion peptide and the trimeric bulk phase of the spike protein. cache = ./cache/cord-281528-xy8j5jiv.txt txt = ./txt/cord-281528-xy8j5jiv.txt === reduce.pl bib === id = cord-287266-sd5izamc author = Song, Zhenhui title = EIF4A2 interacts with the membrane protein of transmissible gastroenteritis coronavirus and plays a role in virus replication date = 2019-04-30 pages = extension = .txt mime = text/plain words = 4398 sentences = 242 flesch = 54 summary = title: EIF4A2 interacts with the membrane protein of transmissible gastroenteritis coronavirus and plays a role in virus replication Using the GST pull-down approach and a CO-IP assay, the M protein was found to interact with porcine intestinal cells via eukaryotic translation initiation factor 4-alpha (EIF4A2), an essential component of the cellular translational machinery. The present study provides mechanistic insight into the interaction between the TGEV M protein and intestinal cells which contributes to the understanding of coronavirus replication and may be useful for the development of novel therapeutic strategies for TGEV infection. In the present study, using yeast two-hybrid screening, seven cellular proteins, including eukaryotic translation initiation factor 4-alpha (EIF4A2), were identified to be M-ligands. Moreover, previous reports have shown that EIF4A2 interacts with VP1 of infectious bursal disease virus (IBD) and inhibits the RNA polymerase activity of IBDV to reduce its replication in host cells (Tacken et al., 2004; Gao et al., 2017) . cache = ./cache/cord-287266-sd5izamc.txt txt = ./txt/cord-287266-sd5izamc.txt === reduce.pl bib === id = cord-282859-uxltqopq author = Rosati, A title = BAG3: a multifaceted protein that regulates major cell pathways date = 2011-04-07 pages = extension = .txt mime = text/plain words = 4431 sentences = 258 flesch = 43 summary = These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. By modulating these pathways, BAG3 appears to mediate cell adaptive responses to stressful stimuli, and its alterations result in altered homeostasis and reduced cytoprotection, explaining why its expression is often found deregulated in a vast series of tumors. 12, 19 In humans, bag3 gene expression is constitutive in myocytes, a few other normal cell types and several primary tumors or tumor cell lines (lymphoid or myeloid leukemias, lymphomas, myeloma, neuroblastoma, pancreas, thyroid, breast and prostate carcinomas, melanoma, osteosarcoma, kidney, colon and ovary cancers, glioblastoma). 67 Similarly to what we described above for apoptosis, the ability of BAG3 to regulate cell adhesion appears to rely on multiple interactions of this protein through different structural domains. cache = ./cache/cord-282859-uxltqopq.txt txt = ./txt/cord-282859-uxltqopq.txt === reduce.pl bib === id = cord-285647-9tegcrc3 author = Estrada, Ernesto title = Fractional diffusion on the human proteome as an alternative to the multi-organ damage of SARS-CoV-2 date = 2020-08-17 pages = extension = .txt mime = text/plain words = 9179 sentences = 533 flesch = 59 summary = By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19. 25, 26 Therefore, we assume here that perturbations produced by SARS-CoV-2 proteins on the human PPI network are propagated by means of diffusive processes. Here, we propose the use of a time-fractional diffusion model on the PPI network of proteins targeted by SARS-CoV-2. We now consider how a perturbation produced by SARS-CoV-2 on a protein mainly expressed in the lungs can be propagated to proteins mainly located in other tissues (see Table S4 in the supplementary material) by a subdiffusive process. Here, we have studied the particular case in which the time-fractional diffusion equation produces a subdiffusive regime, with the use of α = 3/4 in the network of human proteins targeted by SARS-CoV-2. cache = ./cache/cord-285647-9tegcrc3.txt txt = ./txt/cord-285647-9tegcrc3.txt === reduce.pl bib === id = cord-287450-hydy874v author = Wendt, K Ulrich title = Structures and diseases date = 2008 pages = extension = .txt mime = text/plain words = 2768 sentences = 103 flesch = 35 summary = In early September 2007, about 180 structural biologists and biochemists met in the picturesque town of Murnau, located near Staffelsee Lake in the Bavarian alpine upland, to reflect on these questions and discuss recent biostructural data on the molecular determinants of human diseases, including microbial and viral infections, protein misfolding diseases, cancer and metabolic disorders. Starting the session on viral diseases, Rolf Hilgenfeld (University of Lübeck) reviewed the work from his laboratory on proteases of RNA viruses, such as severe acute respiratory syndrome (SARS) coronavirus and coxsackievirus B3, and also highlighted recent structural data on falcipain-2 from Plasmodium falciparum, discussing implications for the design of active-site directed and allosteric inhibitors for these cysteine proteases 14 . Günter Fritz (University of Konstanz) presented the unpublished structure of the ligand binding domain of RAGE, a multiligand receptor for advanced glycation end products, S100 proteins, HMGB1 and amyloid-β, whose activation is key to numerous chronic diseases such as diabetes, inflammation, arteriosclerosis and neurodegeneration, making it a potential therapeutic target 32, 33 . cache = ./cache/cord-287450-hydy874v.txt txt = ./txt/cord-287450-hydy874v.txt === reduce.pl bib === id = cord-284648-yznlgzir author = Varanko, Anastasia title = Recent trends in protein and peptide-based biomaterials for advanced drug delivery date = 2020-08-29 pages = extension = .txt mime = text/plain words = 33501 sentences = 1732 flesch = 42 summary = Albumin is the most abundant protein in human plasma and has a set of properties that make it a unique molecular carrier for drugs: (i) it is a natural physiological carrier of native ligands and nutrients; (ii) it bypasses systemic clearance and degradation by the body's own innate mechanisms, so that it has an exceptionally long half-life of 19 days in humans, and similarly long half-lives in most animal species [123] [124] [125] [126] ; (iii) it preferentially accumulates at sites of vascular leakiness; (iv) it is highly internalized and metabolized by rapidly growing, nutrient-starved cancer cells; and (v) it is biodegradable and has no known systemic toxicity. Other notable examples of albumin-based delivery systems involve the genetic fusion of ABD to various therapeutic proteins including affibodies [165, 166] , human soluble complement receptor type 1 [167] , single chain antibody-drug conjugates [168] , insulin-like growth factor II [169] , immunotoxins [170] , and respiratory syncytial virus subgroup A (RSV-A) G protein (G2Na) [171] . cache = ./cache/cord-284648-yznlgzir.txt txt = ./txt/cord-284648-yznlgzir.txt === reduce.pl bib === id = cord-286603-4p3t0vre author = Duan, Zhiqiang title = TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein date = 2020-06-27 pages = extension = .txt mime = text/plain words = 10674 sentences = 464 flesch = 40 summary = title: TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein Therefore, the reduced viral RNA synthesis and transcription caused by M/NLS mutation might be one of the reasons responsible for the attenuated replication of rSS1GFP-M/NLSm. Virus-host protein interactions based on quantitative proteomics analysis have become important methods in understanding cellular proteins involved in virus replication and pathogenesis [22, 23, 41, 42] . Therefore, together with the above results, we speculated that the relatively decreased expression of DEPs involved in ribosome structure, protein posttranslational modification and trafficking due to the disrupted nuclear accumulation of M protein affected viral protein synthesis and budding, which might be the third reason responsible for the attenuated replication of rSS1GFP-M/NLSm. Inflammatory responses are important aspects of the innate immune system during virus infection. cache = ./cache/cord-286603-4p3t0vre.txt txt = ./txt/cord-286603-4p3t0vre.txt === reduce.pl bib === id = cord-289124-6w2zvvj1 author = Mok, Lawrence title = Proteomic analysis of Pteropus alecto kidney cells in response to the viral mimic, Poly I:C date = 2015-11-02 pages = extension = .txt mime = text/plain words = 5444 sentences = 356 flesch = 57 summary = Here, we investigated the differential protein expression of immortalised Pteropus alecto kidney cells (PaKiT03) following transfection with the viral mimic, Poly I:C. Two complementary proteomic approaches, difference gel electrophoresis (DIGE) and isobaric tagging for relative and absolute quantitation (iTRAQ) were used to quantify changes in protein expression following Poly I:C stimulation at 4, 8 and 20 hr post treatment (hpt). Through iTRAQ analysis we show that Poly I:C up-regulates key glycolytic enzymes at 4 hpt within PaKiT03 cells. The analysis with DIGE of Poly I:C transfected PaKiT03 cells showed over 215 individual spots differentially regulated, however only 25 spots could be unambiguously identified by LC-MS/MS. We further assessed the response of three glycolytic enzymes, α-enolase (Eno1), phosphoglycerate mutase 1 (Pgam1) and triosephosphate isomerase 1 (Tpi1) to Poly I:C across two human (HEK293T and HeLa) and two bat cell lines (PaKiT03, PaLuT02) using immunodetection. cache = ./cache/cord-289124-6w2zvvj1.txt txt = ./txt/cord-289124-6w2zvvj1.txt === reduce.pl bib === id = cord-288673-ku3tmjd3 author = Sabotič, Jerica title = Microbial and fungal protease inhibitors—current and potential applications date = 2012-01-05 pages = extension = .txt mime = text/plain words = 14630 sentences = 689 flesch = 29 summary = Because proteases play essential roles in life and death processes in all living organisms and because peptide bond hydrolysis is irreversible, anomalies in proteolytic activities lead to numerous pathological conditions, including cancer, neurodegenerative disorders and inflammatory and cardiovascular diseases, as well as bacterial, viral and parasitic diseases (Lopez-Otin and Bond 2008; Turk 2006) . Another important oral cavity pathogen involved in periodontal disease, Porphyromonas gingivalis, in addition to a few cysteine proteases (discussed further in the following), produces a serine protease, a prolyl tripeptidyl peptidase PtpA (family S9), which is involved in degrading host connective tissue, providing nutrients for bacterial growth (Banbula et al. Several proteases of the serine catalytic type have also been targeted for the design of specific protease inhibitors for use in cancer treatment, including the urokinase plasminogen activator and matriptase (Abbenante and Fairlie 2005; Bialas and Kafarski 2009; Ulisse et al. cache = ./cache/cord-288673-ku3tmjd3.txt txt = ./txt/cord-288673-ku3tmjd3.txt === reduce.pl bib === id = cord-286217-3uklf2u2 author = Jiang, He-wei title = SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses date = 2020-07-14 pages = extension = .txt mime = text/plain words = 6829 sentences = 423 flesch = 54 summary = Here we construct a SARS-CoV-2 proteome microarray containing 18 out of the 28 predicted proteins and apply it to the characterization of the IgG and IgM antibodies responses in the sera from 29 convalescent patients. We detected the SARS-CoV-2-specific IgG and IgM proteins bound to the array using fluorescent-labeled anti-human antibodies, thereby generating a global assessment of each patient's humoral antibody response. All of the samples and the controls were probed on the proteome microarray, and after data filtering and normalization, we constructed the IgG and IgM profile for each serum and performed clustering analysis to generate heatmaps (Figs. To statistically analyze the IgG responses against SARS-CoV-2 proteins, we calculated the p-values followed by multiple testing correction (or q-values), and applied significant analysis of microarray (SAM) to identify significant positive proteins (Supplementary Fig. 7 and Data 2). cache = ./cache/cord-286217-3uklf2u2.txt txt = ./txt/cord-286217-3uklf2u2.txt === reduce.pl bib === id = cord-286301-7sjw5ci7 author = Sadasivan, Jibin title = Cytoplasmic tail of coronavirus spike protein has intracellular targeting signals date = 2017-04-18 pages = extension = .txt mime = text/plain words = 6243 sentences = 289 flesch = 48 summary = SARS-S-Y was absent from surface in most of the cells and localized at the intracellular compartments (figure 5a), and OC43-S protein was mainly localized in distinct puncta that could represent endocytic structures following internalization from the plasma membrane (figure 5b). Our studies clearly demonstrated that the KXHXX motif is the major intracellular localization signal of the full-length SARS-S protein and the C-terminal proximity is not essential. Our alanine mutation studies on the KXHXX motif confirm the importance of the lysine and histidine in the full-length wild-type HCoV-SARS S protein; the mutant protein showed localization in plasma membrane instead of the usual ER and ERGIC. In contrast, Lysosomal acid phosphatase, also a type I membrane protein with a cytosolic tail GYXXØ motif located 7 residues from both transmembrane domain and the carboxy termini (Tm-RMQAQPPGYRHVADGEDHA) delivered mainly via the cell surface (Braun et al. cache = ./cache/cord-286301-7sjw5ci7.txt txt = ./txt/cord-286301-7sjw5ci7.txt === reduce.pl bib === id = cord-289710-ucguzgdm author = nan title = Yeast Kex1p is a Golgi-associated membrane protein: deletions in a cytoplasmic targeting domain result in mislocalization to the vacuolar membrane date = 1992-12-02 pages = extension = .txt mime = text/plain words = 7986 sentences = 376 flesch = 51 summary = In addition to soluble proteins, the cell surface appears to be the default destination for mammalian ER, Golgi, and lysosomal membrane proteins as removal of their respective retention/targeting signals results in their delivery to the plasma membrane (Machamer and Rose, 1987; Jackson et al., 1990; Williams and Fukuda, 1990) . Kexlp is predicted to be a type I transmembrane protein with a large amino-terminal protease domain in the lumen of the secretory pathway, a single membrane-spanning domain, and a smaller carboxy-terminai domain positioned cytoplasmicaUy. The observation that KEX/cells intracellularly retain Kexlp activity prompted an analysis to determine in which secretory compartment Kexlp resided, and how it achieved such retention. The above results indicated that Kexlp-Hpa was membrane associated, had received glycosyl modifications in the Golgi apparatus, gave wild-type levels of total activity, and was retained intracellularly; yet processed the K1 killer toxin precursor to a lesser extent than Kexlp. cache = ./cache/cord-289710-ucguzgdm.txt txt = ./txt/cord-289710-ucguzgdm.txt === reduce.pl bib === id = cord-287729-pl88otue author = Gray, Stewart M. title = Plant virus proteins involved in natural vector transmission date = 1996-07-31 pages = extension = .txt mime = text/plain words = 2228 sentences = 168 flesch = 59 summary = Viral proteins mediate the binding of plant viruses to vector mouthparts and the transport of virus across vector-cell membranes. They further suggest that the am&-terminal region of the coat-protein monomers assembled into virus particles is not normally available for interaction with the aphids, but that HC mediates a conformational change in the amino termiof thecoat protein that allows binding of the virus ;o the aphid (Fig. 4C) .mission is regulated mainly by the codt protein'". Site-specific mutagenesis of cucumber mosaic virus (CuMV) has identified two regions of the coat protein thar are involved in efficient transmission, and has pinpointed the amino acids needed<'. These observations biggest that one or a few amino acid changes in the coat protein could alter the vectortransmission phenotype by pre\ enring direct interaction between the virus and the vector. the environment wtthln the food canal or binding of the virus tc) the vector, all resulting in the exposure >f cleavage sites on the coat proteins. cache = ./cache/cord-287729-pl88otue.txt txt = ./txt/cord-287729-pl88otue.txt === reduce.pl bib === id = cord-287477-aios0h8s author = Sicari, Daria title = Role of the early secretory pathway in SARS-CoV-2 infection date = 2020-07-28 pages = extension = .txt mime = text/plain words = 6483 sentences = 359 flesch = 44 summary = CoV-2 infection starts when its spike (S) protein binds to angiotensin I-converting enzyme 2 (ACE2) receptors on the host cell membrane (Lake, 2020; Letko et al., 2020) . Thus, virion spread critically depends on recruiting the most efficient secretory machineries of host cells (Su et al., 2016; Proteins of the early secretory pathway bound by SARS-CoV-2 As the entire world asks for ways to stop CoV-2, many laboratories are investigating the virus's Achilles heel(s). The role of glycosylation and protein quality control in SARS-CoV-2 infections Most CoVs bud at the ERGIC level ( Fig. 1) and are then transported along the exocytic pathway (Klumperman et al., 1994; Stertz et al., 2007) . We observed enrichment for five host-derived virus-interacting proteins (GOLGB1, PDE4DIP, TOR1A, HMOX1, and HYOU1) involved in different processes and related to quality control and ER-Golgi homeostasis maintenance. cache = ./cache/cord-287477-aios0h8s.txt txt = ./txt/cord-287477-aios0h8s.txt === reduce.pl bib === id = cord-286970-4pl95r0o author = Mamipour, Mina title = An overview on molecular chaperones enhancing solubility of expressed recombinant proteins with correct folding date = 2017-04-12 pages = extension = .txt mime = text/plain words = 4994 sentences = 279 flesch = 50 summary = In this article, we attempted to review cytoplasmic chaperones such as Hsp families and periplasmic chaperones including; generic chaperones, specialized chaperones, PPIases, and proteins involved in disulfide bond formation. Numerous studies demonstrate positive effects of molecular chaperons on correct folding formation of recombinant protein and prevention of IBs formation in the cytoplasm and periplasm [17, 18] . In this review we focused on cytoplasmic and periplasmic chaperones category and their applications in recombinant protein expression with correct folding. The Hsp90 family are highly conserved and proteins, which exist in all organisms from bacteria to humans and their expressions rises in response to the stress conditions in prokaryotic and eukaryotic LolA (B,C,D,E) periplasm space, Inner membrane and Outer membrane rapid transfer of associated lipoproteins ATP (+) [108] PapD and its family periplasm space and Outer membrane biogenesis of pilus (−) [163] FimC periplasm space interacts with each pilus subunit (−) [164] cells. cache = ./cache/cord-286970-4pl95r0o.txt txt = ./txt/cord-286970-4pl95r0o.txt === reduce.pl bib === id = cord-281552-zfjy3m3i author = Alsaadi, Entedar A. J. title = Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus date = 2020-09-22 pages = extension = .txt mime = text/plain words = 4781 sentences = 205 flesch = 49 summary = Here, we test E-derived peptides for membrane binding activity in vitro and confirm those identified as positive in the context of the full length protein expressed in two different cell types. Relative densitometry of the HSP and LSP bands revealed significant differences among the mutants with regard to their localisation to the different membrane fractions of E expressing insect cells ( Figure 5B ) and confirmed a role for the amphipathic MHV CoV E 50-64 peptide in membrane interaction. An amphipathic helix, EPTM, detected in the post-TM region of E, was suggested by bioinformatics analysis and assessed for direct membrane interaction in vitro by binding to GUVs. For comparison, the predicted E protein TM domain, ETM, and an established membrane active peptide from the influenza M2 protein were also included. Following expression of the complete E protein with mutations in the same identified peptide, altered membrane binding in two distinct cell types, mammalian and insect, was apparent. cache = ./cache/cord-281552-zfjy3m3i.txt txt = ./txt/cord-281552-zfjy3m3i.txt === reduce.pl bib === id = cord-287410-boxxlopy author = Devi, Arpita title = In silico designing of multi-epitope vaccine construct against human coronavirus infections date = 2020-08-10 pages = extension = .txt mime = text/plain words = 7189 sentences = 446 flesch = 60 summary = Band T-cell epitopes of the spike proteins have been predicted and designed into a multi-epitope vaccine construct. To predict the probable immune response of the designed multi-epitope vaccine construct in human immune system, in silico immune simulations were conducted using the C-ImmSim server (http://150.146.2.1/C-IMMSIM/index.php) (Rapin et al., 2010) . C-ImmSim is a novel in silico approach for the study of the mammalian immune system The tool is a combination of a mesoscopic scale simulator of the immune system with machine learning techniques for molecular-level predictions of major histocompatibility complex (MHC)-peptide-binding interactions, linear B-cell epitope discovery, and protein-protein potential estimation. The antigenicity of the vaccine construct including the adjuvant sequence and His-tag was predicted by the VaxiJen 2.0 server to be 0.6452 with a bacteria model at a threshold of 0.4. cache = ./cache/cord-287410-boxxlopy.txt txt = ./txt/cord-287410-boxxlopy.txt === reduce.pl bib === id = cord-280878-1kt51viz author = To, Janet title = Targeting the Channel Activity of Viroporins date = 2016-01-07 pages = extension = .txt mime = text/plain words = 15297 sentences = 701 flesch = 47 summary = For other viroporins, these studies are still mostly in their infancy, although a highresolution structure of the hepatitis C virus (HCV) p7 protein has been recently described (Ouyang et al., 2013) that may be useful for the rational design of p7 channel inhibitors in the future. Structure and ion channel activity of the human respiratory syncytial virus (hRSV) small hydrophobic protein transmembrane domain The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels NMR structure and ion channel activity of the p7 protein from hepatitis C virus Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells Structure and inhibition of the drug-resistant S31N mutant of the M2 ion channel of influenza A virus cache = ./cache/cord-280878-1kt51viz.txt txt = ./txt/cord-280878-1kt51viz.txt === reduce.pl bib === id = cord-290445-vb53bih9 author = Ahmed, Shiek SSJ title = Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery date = 2020-04-23 pages = extension = .txt mime = text/plain words = 3793 sentences = 208 flesch = 42 summary = Secondly, the viral replication machinery network from SET-B with 332 seed proteins extended to 1486 neighboring proteins with 11438 interacting edges which representing the mechanism attributed to evasion of the SARS-CoV2 genome into the host. Similarly, the viral replication machinery network was acquired with 1522 proteins with 9747 interacting edges showing the complex SARS-CoV-2 mechanism in the human lungs. These common molecules represent the inter-connecting mechanism involved in the transcription machinery, immune response, cell growth and/or maintenance, transport, metabolism, protein metabolism, cell communication and signal transduction that activated upon virus binding and has been subsequently utilized for viral replication process (S5 Table) Also mapping with other viral infection dataset, 50 hub proteins of the replication machinery network have noticed in influenza virus infection (S4 Table) , which suggests SARS-CoV2 and influenza may have a similar mode of host infection machinery [17] . The molecular pathways of interconnecting protein hubs could be the intermediate phase that connects the receptor activation mechanism and viral replication process (Fig 10) . cache = ./cache/cord-290445-vb53bih9.txt txt = ./txt/cord-290445-vb53bih9.txt === reduce.pl bib === id = cord-290290-wyx9ib7s author = Sinegubova, Maria V. title = High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date = 2020-11-05 pages = extension = .txt mime = text/plain words = 5978 sentences = 304 flesch = 49 summary = title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. Previously we have developed the plasmid vector p1.1, containing large fragments of non-coding DNA from the EEF1A1 gene of the Chinese hamster and fragment of the Epstein-Barr virus long terminal repeat concatemer [21] and employed it for unusually high-level expression of various proteins in CHO cells, including blood clotting factors VIII [22] , IX [23] , and heterodimeric follicle-stimulating hormone [24] . We have proposed that SARS-CoV-2 RBD, suitable for in vitro diagnostics use, may be expressed in large quantities by stably transfected CHO cells, bearing the EEF1A1-based plasmid. cache = ./cache/cord-290290-wyx9ib7s.txt txt = ./txt/cord-290290-wyx9ib7s.txt === reduce.pl bib === id = cord-290638-7ro72sv3 author = Lenstra, Johannes A. title = Antigenicity of the peplomer protein of infectious bronchitis virus date = 1989-01-31 pages = extension = .txt mime = text/plain words = 3960 sentences = 230 flesch = 53 summary = Abstract To study the antigenic structure of the peplomer protein of the avian coronavirus infectious bronchitis virus, fragments from the peplomer gene were generated by restriction-enzyme cleavage or by limited DNase digestion and inserted in the Escherichia coli expression plasrnid pEX (Stanley and Luzio, 1984). Recombinants expressing the IBV gene fragments were selected by immunoscreening with a rabbit antiserum or, when the expression product was not recognized antigenically, by hybridization followed by gel electrophoresis of the protein expression products. Figure 2 (C) shows a Western blot of hybrid proteins screened with this MAb. The strong binding to fragments p2, s4, psl and ps2 localizes the epitope of MAb 26.1 between residues 390 and 612, the same region that is recognized by all polyclonal sera. The localization of epitopes within stretches of 10-20 residues in several coronaviruses (Fig. 4 , unpublished results) demonstrates that the binding of antibody does not depend on particular flanking sequences, and that any nativelike folding of the epitope in the hybrid protein is confined to the same small region. cache = ./cache/cord-290638-7ro72sv3.txt txt = ./txt/cord-290638-7ro72sv3.txt === reduce.pl bib === id = cord-292958-k5d5fo3i author = Sekhon, Simranjeet Singh title = Porcine epidemic diarrhea (PED) infection, diagnosis and vaccination: A mini review date = 2017-01-04 pages = extension = .txt mime = text/plain words = 7430 sentences = 299 flesch = 41 summary = Porcine epidemic diarrhea virus (PEDV) is a main etiology causing severe enteric disease in piglets with clinical signs of anorexia, vomiting, diarrhea and dehydration resulting in loss of condition and death within a few days. Many techniques are available for the detection of PEDV from fecal materials, small infected intestines sample, including reverse transcript polymerase chain reaction (RT-PCR), direct immunofluorescence tests (IF), indirect fluorescence antibody tests (IFA), immunohistochemistry techniques (IHC), in situ hydridization, electron microscopy and enzyme-linked immunosorbent assays (ELISA) 2 . (2012) used the Vero cell cultures to isolate CHGD-01 PEDV strain as well as employed direct immunofluorescence assay and EM technique to investigate its specific cytopathic effects in the outbreak of diarrhea in Guangdong (South China) swine 18 . The RT-PCR system in this study could effectively detect PEDV RNA from viral mixtures or small intestinal/ fecal samples in very low number of virus within short time. cache = ./cache/cord-292958-k5d5fo3i.txt txt = ./txt/cord-292958-k5d5fo3i.txt === reduce.pl bib === === reduce.pl bib === id = cord-289026-v09m2fzw author = Sun, Yan-gang title = Characterization of the interaction between recombinant porcine aminopeptidase N and spike glycoprotein of porcine epidemic diarrhea virus date = 2018-10-01 pages = extension = .txt mime = text/plain words = 5232 sentences = 340 flesch = 56 summary = Infection by its causative agent PED virus (PEDV), an Alpha-coronavirus, was previously proven to be mediated by its spike (S) glycoprotein and a cellular receptor porcine aminopeptidase N (pAPN). We then assayed the purified target proteins through immunogenicity tests, PEDV binding interference assays, circular dichroism (CD) measurements, pAPN activity assay and structural determination, demonstrating that they were biologically functional. Based on the results above, recombinant pAPN ectodomain was obtained as dimers, and PEDV S1 or S1t protein existed as monomers, which showed similar natures of mammalian APN [43] and other coronavirus S proteins [48] [49] [50] as previously reported. In the current study, three canonical assays were carried out to characterize the interaction between pAPN ectodomain and PEDV S1 or S1t protein since these functional target proteins were successfully prepared. Identification and comparison of receptor binding characteristics of the spike protein of two porcine epidemic diarrhea virus strains cache = ./cache/cord-289026-v09m2fzw.txt txt = ./txt/cord-289026-v09m2fzw.txt === reduce.pl bib === === reduce.pl bib === id = cord-290904-ngvhk0qy author = Zheng, Zhiqiang title = Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2 date = 2020-07-16 pages = extension = .txt mime = text/plain words = 4471 sentences = 246 flesch = 57 summary = In this study, we aim to verify if the sequence of the immunogen used to generate mAb 1A9, as well as three other mAbs, is conserved in different coronaviruses and if these mAbs bind to the S protein of SARS-CoV-2 expressed in mammalian cell lines. IF analysis performed on transiently transfected COS-7 cells showed binding of the four mAbs to this S protein fragment of SARS-CoV-2 ( Figure 2B ). Utility of monoclonal antibody 1A9 for detection of S protein in a sandwich ELISA format and in SARS-CoV-2 infected cells Based on indirect ELISA data, mAb 1A9 has the strongest binding to S protein when compared with the other three mAbs. Hence, a sandwich ELISA was performed to determine if it can be paired with the human mAb CR3022 which is known to bind to the S1 subunit of SARS-CoV-2. cache = ./cache/cord-290904-ngvhk0qy.txt txt = ./txt/cord-290904-ngvhk0qy.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-295381-0dqu3p3y author = Kamal, Adeela title = Therapeutic and diagnostic implications of Hsp90 activation date = 2004-06-01 pages = extension = .txt mime = text/plain words = 5102 sentences = 211 flesch = 37 summary = Recent work has identified the role of Hsp90 in multiple signal transduction pathways and revealed that the molecular mechanism of tumor selectivity by Hsp90 inhibitors is the result of an activated, high-affinity conformation of Hsp90 in tumors. A recent study reported that the Hsp90 in tumor cells is maintained in an activated conformation by the formation of multi-chaperone complexes that have increased ATPase activity and 100-fold greater binding affinity for 17-AAG compared with the uncomplexed, latent form of Hsp90 that is present in normal cells [28] . A model for Hsp90-dependent malignant progression has been proposed in which, as tumor cells gradually accumulate mutant and overexpressed signaling proteins, Hsp90 becomes engaged in the active chaperoning and stabilization of oncoproteins and adopts a high-affinity form that is induced by bound co-chaperone proteins ( Figure 3 ) [28] . FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinases cache = ./cache/cord-295381-0dqu3p3y.txt txt = ./txt/cord-295381-0dqu3p3y.txt === reduce.pl bib === === reduce.pl bib === id = cord-296794-ml2luc1t author = Sollner, Johannes title = Analysis and prediction of protective continuous B-cell epitopes on pathogen proteins date = 2008-01-07 pages = extension = .txt mime = text/plain words = 8006 sentences = 387 flesch = 41 summary = This work assesses in how far correlation between antigenicity, variability, post-translational modifications and protectivity/functional relevance can be put to use in a predictive model without the availability of 3D data. Classification into presumably protective or non-protective epitopes is conducted using three independently determined parameters: predicted B-cell antigenicity, sequence variability and conservation of post-translational modification motifs. These results are relativated later in this work when using only potentially relevant domains of a protein antigen, indicating systematic problems of the way B-cell epitope prediction validation is usually conducted. Briefly, proteins were completely scored for antigenicity/protectivity but amino-acid scores in regions outside domains assumed to be surface exposed were set to 0 thus leading to a generic classification as non-protective. On this compilation protectivity prediction using PCA19 in combination with variability and modification likelihood performed significantly better after domain-accessibility filtering as measured by AROC values, while without filtering performance was comparable (although again slightly better) to antigenicity validation results on the Blythe et.al validation-set. cache = ./cache/cord-296794-ml2luc1t.txt txt = ./txt/cord-296794-ml2luc1t.txt === reduce.pl bib === id = cord-292985-w62xaa4f author = Römer, Rudolf A. title = Flexibility and mobility of SARS-CoV-2-related protein structures date = 2020-07-12 pages = extension = .txt mime = text/plain words = 5201 sentences = 341 flesch = 61 summary = We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. 34 We have performed our analysis through multiple conformational steps starting from the crystal structures of SARS-CoV-2-related proteins as currently deposited in the PDB. In Fig. 1 (a) we see that for the crystal structure of SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain (PDB:6m3m), the largest rigid cluster in the pristine structure, i.e. at E cut = 0, largely remains rigid through the dilution process of consecutively lowering E cut values. Last, a protein with 2nd-order rigidity should have the most complex behaviour in terms of flexibility since new possible mobility can be expected throughout the range of E cut values. Moving along directions proposed by an elastic normal model analysis of the crystal structure, we can therefore construct possible motion trajectories that are fully consistent with the bond network and steric constraints. cache = ./cache/cord-292985-w62xaa4f.txt txt = ./txt/cord-292985-w62xaa4f.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-292688-w4zvfkyl author = Tooze, Sharon A title = Biogenesis of secretory granules in the trans-Golgi network of neuroendocrine and endocrine cells date = 1998-08-14 pages = extension = .txt mime = text/plain words = 8150 sentences = 320 flesch = 45 summary = An alternative hypothesis is that there is very little constitutive secretion originating from the TGN of regulated cells, and that most molecules in the biosynthetic pathway exit into ISGs. In the ISG, the non-secretory granule proteins would presumably be sorted from the regulated secretory proteins via interaction with a receptor and removed from the ISG in constitutive-like vesicles. Depending on the cargo, distinct mechanisms could be used for selection to increase the e¤ciency of removal of nonsecretory granule proteins from the maturing ISGs. While the mechanisms involved in the formation of both constitutive and regulated secretory vesicles from the TGN is largely unknown there have been recent reports which suggest that both these budding reactions maybe unique in that they function independently of known coat proteins. In the PC12 cell assay, the same e¡ect was observed with [AlF 4 ] À and several other lines of evidence demonstrated that heterotrimeric GTP-binding proteins are involved in the regulation of post-Golgi vesicle formation (see [71] for review). cache = ./cache/cord-292688-w4zvfkyl.txt txt = ./txt/cord-292688-w4zvfkyl.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-301128-woe6knpv author = Joyeux, Marc title = Requirements for DNA-bridging proteins to act as topological barriers of the bacterial genome date = 2020-08-12 pages = extension = .txt mime = text/plain words = 4507 sentences = 226 flesch = 51 summary = The results presented in this article reveal that the formation of DNA loops is by no means sufficient to create topologically independent domains and that DNA-bridging proteins must exert rather strong constraints on their binding sites in order to act as topological barriers: They must block the diffusion of the excess of twist through both binding sites and must additionally block the rotation of one DNA segment relative to the other one. We report below on our efforts to determine the minimal set of mandatory properties that allow molecular bridges to act as topological barriers and block the diffusion of torsional stress in out-of-equilibrium supercoiled chains. Since DNAbridging proteins form DNA loops by dynamically cross-linking widely separated DNA sites, the question amounts here to determine the constraints that must be imposed to beads α and β J o u r n a l P r e -p r o o f to divide the circular DNA chain into two topologically independent loops. cache = ./cache/cord-301128-woe6knpv.txt txt = ./txt/cord-301128-woe6knpv.txt === reduce.pl bib === id = cord-294712-kvvxmvqo author = Pelosse, Martin title = MultiBac: from protein complex structures to synthetic viral nanosystems date = 2017-10-30 pages = extension = .txt mime = text/plain words = 5379 sentences = 272 flesch = 38 summary = The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. We then turned our attention to eukaryotic methods, specifically an expression vector system relying on a recombinant baculovirus, to infect insect cell cultures for producing the complexes in which we had interest. This particular feature, and the-at least conceptually-relative ease of manipulating baculovirus in the laboratory by non-expert users, was exciting and led us on to the development of MultiBac: a baculovirus/insect cell system specifically engineered for expressing functional multiprotein complexes in the quality and quantity required for high-resolution structural and mechanistic studies [7] [8] [9] [10] [11] . The introduced genome alterations resulted in a virus that exhibited delayed lysis of the insect cells, allowing the production of recombinant protein complexes at very high levels while the cells seemingly remained intact [11] . The MultiBac baculovirus/insect cell expression vector system for producing complex protein biologics cache = ./cache/cord-294712-kvvxmvqo.txt txt = ./txt/cord-294712-kvvxmvqo.txt === reduce.pl bib === id = cord-294945-hcf7gsv8 author = Lin, K.H. title = Comparative proteomic analysis of cauliflower under high temperature and flooding stresses date = 2015-02-12 pages = extension = .txt mime = text/plain words = 8221 sentences = 414 flesch = 49 summary = The objectives of this study were to identify the proteins that were differentially regulated and the physiological changes that occurred during different time periods in 'H41', 'H69', and 'H71' when responding to treatments of flooding, 40 °C, and both stresses combined. By the comparative proteomic analysis, 85 protein peaks that were differentially expressed in response to combination treatments at 0, 6, and 24 h, 69 (33 in 'H41', 29 in 'H69', and 9 in 'H71') were identified, of which were cultivar specific. Compared to NFC treatment at 0 h, NFH treatment for 6 h showed that the abundances of peaks 271 (phosphoserine aminotransferase), 272 (imidazole glycerol phosphate synthase subunit hisF), Table 6 Identification of differentially expressed proteins found in cauliflower 'H71' plants by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in comparison to combination treatments for 0 and 6 h. cache = ./cache/cord-294945-hcf7gsv8.txt txt = ./txt/cord-294945-hcf7gsv8.txt === reduce.pl bib === id = cord-304040-64obh7i3 author = Sande, Charles J. title = Untargeted analysis of the airway proteomes of children with respiratory infections using mass spectrometry based proteomics date = 2018-09-14 pages = extension = .txt mime = text/plain words = 5041 sentences = 250 flesch = 43 summary = Our proteomic experiments tested the optimal approach to characterize airway proteome on swab samples eluted in UTM based on the number of proteins identified without BSA depletion (Total proteome: Protocol A) and with its depletion using a commercial kit; Allprep, Qiagen (cellular proteome: Protocol B, Ci, and Cii). Compared to previous mass-spectrometry-based proteomics studies of the upper airway, the number of proteins identified in protocol Cii, vastly exceeded the number of proteins reported in previously published reports 14, 20, 22, 23, 25, 26, 28, 29 . Further characterisation the proteomes identified in protocol Cii, was done by evaluating the expression levels of marker proteins of resident naso-oro-pharyngeal epithelial cells. In addition to these definitive upper-airway proteins, we found a consistently high level of expression of mucins (MUC1 & 5) -the main component of respiratory tract mucus -and mucosal-associated keratins, KRT4 and KRT13. Our search of T-cell associated marker and effector proteins, did not identify any such proteins in the upper-airway proteomes of any of the children in this study. cache = ./cache/cord-304040-64obh7i3.txt txt = ./txt/cord-304040-64obh7i3.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-305602-yzc4bosn author = Llano, Manuel title = Chapter Seven Defining Pharmacological Targets by Analysis of Virus–Host Protein Interactions date = 2018-12-31 pages = extension = .txt mime = text/plain words = 5909 sentences = 324 flesch = 41 summary = This higher than expected connectivity suggests that the direct interactions of viral proteins with host factors allow the access of the virus to cellular complexes. For example, in a TAP-MS experiment were mapped 3787 complex associations between 54 viral proteins from different viruses and 1079 host proteins (Rozenblatt-Rosen et al., 2012) , highlighting the high degree of connectivity of the interacting proteins. As discussed above, some of the host factors predicted, by the combined transcriptional profiling and in silico analyses, to interact with host proteins implicated in direct binary contacts with influenza proteins (Y2H interactors) were demonstrated to influence viral replication in functional screenings (Shapira et al., 2009 ). Most of the small molecules interfering with PPIs bind directly to the implicated surfaces of interactions (orthosteric modulators) by targeting hot spot residues or by molecular mimicry of elements of secondary structures (Arkin et al., 2014; Basse et al., 2016; Fry, 2006; Wells & McClendon, 2007; Yin & Hamilton, 2005) . cache = ./cache/cord-305602-yzc4bosn.txt txt = ./txt/cord-305602-yzc4bosn.txt === reduce.pl bib === id = cord-300418-s4wt5gim author = Bedford, Lynn title = Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets date = 2010-12-10 pages = extension = .txt mime = text/plain words = 13080 sentences = 640 flesch = 37 summary = In this Review, we first provide an overview of the enzyme classes in the UPS and UBL pathways that represent potential therapeutic targets, highlighting considerations that are important for drug discovery and recent progress in the development of small-molecule inhibitors. Studies using NF-κB-dependent human cancer models have demonstrated increased levels of the CRL1β TRCP substrate pIκBα and inhibition of NF-κB activity and apoptosis 116, 117 , suggesting the feasibility of NAE inhibition for the treatment of disease that is associated with constitutively active NF-κB signalling 112 The recent discovery of the importance of linear ubiquitin chains in NF-κB activation extends the complexity of the regulation of the system. As expected, ubiquitin-dependent processes, including the degradation of ubiquitylated proteins by the 26S proteasome, by autophagy and in the endosome-lysosome pathway, have central roles in neuronal development, homeostasis and disease. cache = ./cache/cord-300418-s4wt5gim.txt txt = ./txt/cord-300418-s4wt5gim.txt === reduce.pl bib === id = cord-298759-j965t808 author = Jiang, Nan title = Development of a robust Escherichia coli-based cell-free protein synthesis application platform date = 2020-10-17 pages = extension = .txt mime = text/plain words = 5253 sentences = 298 flesch = 55 summary = The Escherichia coli-based system was chosen in this study, and the model protein deGFP was expressed to explore a more efficient cell-free system. To overcome these problems, cell-free protein synthesis (CFPS) has received new attention as an emerging synthetic biology technology, because it is an open system, not limited by cell growth or cell membrane, and it allows the use of various reaction formats. The selection of extracts, the size of the plasmid, the molecular crowding effect and the metal ion J o u r n a l P r e -p r o o f effect, which are important component parameters, were explored to improve the protein expression efficiency. Based on the optimized CFPS systems, the cell-free fundamental scientific research platform, primary screening platform, and portable biomolecular synthesis platform were established. Therefore, researchers need to optimize the metal ions and the corresponding concentration for the best cell-free protein synthesis. cache = ./cache/cord-298759-j965t808.txt txt = ./txt/cord-298759-j965t808.txt === reduce.pl bib === id = cord-302009-oqc21fah author = Geng, Xindu title = Protein folding liquid chromatography and its recent developments() date = 2007-04-15 pages = extension = .txt mime = text/plain words = 6669 sentences = 334 flesch = 49 summary = Protein folding liquid chromatography (PFLC) is a new method developed in recent years, and it is widely used in molecular biology and biotechnology. When it is used in protein folding, the bioactivity recovery increases, the folded protein can be easily separated from misfolded forms, protein concentration after refolding is relatively high, and it is easy to scale up and automate, therefore it is regarded as an efficient, and close to ideal refolding method [1, 2] . In addition, by continuously changing the components of the mobile phase, different proteins can be separated with suitable folding conditions to refold and simultaneously purify in only one chromatographic run. Chaperone solvent plug SEC proposed by Liu and Chang [16] could obviously reduce precipitates formed before denatured protein entered the top of the column, and relatively high mass recovery was obtained. [57] recently proposed a relatively versatile refolding method using IEC with a silica-based weak cation exchanger, very high mass and bioactivity recoveries were obtained for denatured lysozyme. cache = ./cache/cord-302009-oqc21fah.txt txt = ./txt/cord-302009-oqc21fah.txt === reduce.pl bib === id = cord-300796-rmjv56ia author = nan title = The signal sequence of the p62 protein of Semliki Forest virus is involved in initiation but not in completing chain translocation date = 1990-09-01 pages = extension = .txt mime = text/plain words = 8031 sentences = 405 flesch = 57 summary = In this work we show that the p62 protein of Semliki Forest virus contains an uncleaved signal sequence at its NH2-terminus and that this becomes glycosylated early during synthesis and translocation of the p62 polypeptide. As the glycosylation of the signal sequence most likely occurs after its release from the ER membrane our results suggest that this region has no role in completing the transfer process. Furthermore, the p62-reporter hybrid should be translocated across microsomal membranes and possibly glycosylated at Asn~3 of the p62 sequence if the 40 residues long NH2-terminal p62 peptide carries a signal sequence. This must involve Asn~3 of the p62 peptide as it is part of the only potential glycosylation site on the hybrid polypeptides (Garoff et al., 1980 ; references on dhfr sequence in legend to Fig. 1) , Finally, we can also conclude that the p62 signal sequence does not provide a stable membrane anchor to the translocated chain. cache = ./cache/cord-300796-rmjv56ia.txt txt = ./txt/cord-300796-rmjv56ia.txt === reduce.pl bib === id = cord-304343-m7tbdfri author = Khandia, Rekha title = A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy date = 2019-07-03 pages = extension = .txt mime = text/plain words = 20281 sentences = 1088 flesch = 32 summary = Similarly, inhibiting the mTOR signaling pathway can prevent apoptosis and even enhance necroptosis, whereas starvation, which induces autophagy, protects cells from zVAD-mediated necroptotic death [194] . For instance, autophagy has been demonstrated to be actively involved in the replication of influenza A virus (IAV), which induces autophagosome formation during the early phase of infection and later inhibits autophagosomal maturation by preventing autophagosomal-lysosomal fusion and promoting autophagosomes to accumulate in virus-infected cells [253] . (5) A novel anti-cancer molecule, HA15, which targets HSPA5/BIP was shown to induce endoplasmic reticulum stress and increase the unfolded protein response, resulting in cancer cell death through autophagy and apoptosis. (5) A novel anti-cancer molecule, HA15, which targets HSPA5/BIP was shown to induce endoplasmic reticulum stress and increase the unfolded protein response, resulting in cancer cell death through autophagy and apoptosis. In addition, the novel anti-cancer molecule HA15, which targets HSPA5/BIP, was shown to induce ER stress and increase the unfolded protein response, resulting in cancer cell death via autophagy and apoptosis [304] . cache = ./cache/cord-304343-m7tbdfri.txt txt = ./txt/cord-304343-m7tbdfri.txt === reduce.pl bib === id = cord-298251-u36lb44w author = Donaldson, Julie G. title = Arf Family G Proteins and their regulators: roles in membrane transport, development and disease date = 2011-05-18 pages = extension = .txt mime = text/plain words = 10702 sentences = 519 flesch = 44 summary = Members of the ADP-ribosylation factor (ARF) family of guanine-nucleotide-binding (G) proteins, including the ARF-like (ARL) proteins and SAR1, regulate membrane traffic and organelle structure by recruiting cargo-sorting coat proteins, modulating membrane lipid composition, and interacting with regulators of other G proteins. ARF proteins at the trans-Golgi network (TGN) also recruit heterotetrameric clathrin adaptor protein 1 (AP1), AP3 and AP4, as well as the three monomeric Golgi-localized, γ-ear-containing, ADP-ribosylation factor-binding Figure 1 | The domain structure and regulation of ARF and ARLs. a | A schematic of representative ADP-ribosylation factor (ARF), SAR1 and ARF-like (ARL) proteins, indicating the conserved amino-terminal amphipathic helix and the protein-specific lipid modifications at the N terminus. ARF6 at the plasma membrane can regulate the membrane lipid composition, alterations in cortical actin to drive protrusions (for example, during cell migration), and endocytosis of ligand-activated guanine-nucleotide-binding (G) protein-coupled receptors (GPCR) via clathrin-dependent endocytosis. cache = ./cache/cord-298251-u36lb44w.txt txt = ./txt/cord-298251-u36lb44w.txt === reduce.pl bib === id = cord-305143-mqd4ioj4 author = Zmasek, Christian M. title = Classification of human Herpesviridae proteins using Domain-architecture Aware Inference of Orthologs (DAIO) date = 2019-01-06 pages = extension = .txt mime = text/plain words = 7266 sentences = 367 flesch = 44 summary = Coupled with their genome complexity and the availability of numerous complete genome sequences, this deep evolutionary history makes herpesviruses a tractable and informative model to study virus genome evolution at the levels of gene duplication and protein domain rearrangement. In addition, the gene tree for human herpesvirus uracil DNA glycosylases ( Fig. 1B ) precisely recapitulates the herpesvirus species tree (Fig. 1A) ; therefore, this protein family can be inferred to have evolved from a single common ancestor and without any gene duplications or domain rearrangements (see Table 2 for virus-specific gene names). Phylogenetic analysis of human herpesvirus DNA polymerase proteins, plus related proteins from selected mammalian herpesviruses, shows that, similar to the glycoprotein B family, DNA polymerases of the Herpesviride evolved without gene duplication. cache = ./cache/cord-305143-mqd4ioj4.txt txt = ./txt/cord-305143-mqd4ioj4.txt === reduce.pl bib === id = cord-295351-0zr2e8lh author = Mohd Ropidi, Muhammad Izzuddin title = Endoplasmic reticulum: a focal point of Zika virus infection date = 2020-01-20 pages = extension = .txt mime = text/plain words = 7845 sentences = 389 flesch = 35 summary = Following ZIKV infection, the accumulation of misfolded virus polyproteins in the ER lumen overwhelms the ER protein-folding capacity leading to ER stress and triggers the activation of the UPR (Fig. 2) [47] . Following the dissociation of GRP78 that unmasks the GLS, ATF6 translocate to the Golgi apparatus and undergoes sequential proteolytic processing by Fig. 2 ZIKV-induced ER stress initiates host cell unfolded protein response (UPR). ZIKV infection induces ER stress due to the increased amount of unfolded/misfolded viral (red strand) and host cell (grey strand) protein aggregates in the ER lumen. To summarize, ZIKV virus bypasses the UPR by inhibiting stress granules assembly and reticulophagy to ensure continuous viral protein translation and virion production while simultaneously protecting the virus from host cell defense mechanisms. cache = ./cache/cord-295351-0zr2e8lh.txt txt = ./txt/cord-295351-0zr2e8lh.txt === reduce.pl bib === id = cord-298922-k568hlf4 author = Sun, Dongbo title = Analysis of protein expression changes of the Vero E6 cells infected with classic PEDV strain CV777 by using quantitative proteomic technique date = 2015-06-15 pages = extension = .txt mime = text/plain words = 5192 sentences = 244 flesch = 48 summary = Among the disease-related functions, certain anti-viral pathways and proteins, such as the RIG-I-like receptor, Rap1, autophagy, mitogen-activated protein kinase, PI3K-Akt and Jak-STAT signaling pathways, and integrin β2/β3 and cystatin-C proteins, represented potential factors in PEDV infection. In our current study, we used a quantitative proteomics approach based on an iTRAQ tandem mass spectrometry (MS/MS) technique to identify proteins differentially expressed between PEDV-infected and mock-infected Vero E6 cells. To verify the differential expression of the selected DEPs, equivalent volumes of the cell lysate replicates from the PEDV-infected (V1-V3) and mock-infected (C1-C3) Vero E6 cells were pooled into the V and C samples, respectively, and western blotting was performed as described above, with the following exceptions: a 1:1000 dilution of the polyclonal antibodies anti-␤ tubulin, anti-integrin-␤3, anti-cystatin-C, anti-protein S100-A2, anti-apolipoprotein E4, and anti-centrin from rabbit (Beijing Biosynthesis Biotechnology, Beijing, China) was used as the primary antibody, and a 1:5000 dilution of the HRP-conjugated goat anti-rabbit IgG (Sigma-Aldrich, St. Louis, USA) was used as the secondary antibody. cache = ./cache/cord-298922-k568hlf4.txt txt = ./txt/cord-298922-k568hlf4.txt === reduce.pl bib === id = cord-302414-g5onwhg1 author = Tahir ul Qamar, Muhammad title = Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2 date = 2020-09-16 pages = extension = .txt mime = text/plain words = 6780 sentences = 434 flesch = 47 summary = Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast Band Tcell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. The purpose of this study was to pinpoint the potential T-cell and B-cell epitopes from SARS-CoV-2 structural proteins which can be further joined through adjuvant and linkers to design a multiepitope-based subunit vaccine (MESV). Here, we explored the development of epitope-based vaccines targeting the structural proteins (S, M, and E) of the SARS-CoV-2. Taken together, we characterized SARS-CoV-2 structural proteins (S, E, and M) for antigenic epitopes and proposed a potential MESV utilizing various immunoinformatics and computational approaches. cache = ./cache/cord-302414-g5onwhg1.txt txt = ./txt/cord-302414-g5onwhg1.txt === reduce.pl bib === id = cord-303494-tofch4j7 author = Bai, Juan title = Identification of VP1 peptides diagnostic of encephalomyocarditis virus from swine date = 2014-12-30 pages = extension = .txt mime = text/plain words = 3854 sentences = 198 flesch = 57 summary = In order to map the minimal sequences of the epitopes recognized by McAbs, the series of truncated recombinant proteins were used in Western blot was to identify the reactivity of each of 10 anti-VP1 McAbs. The results showed that McAbs (6E11, 7A7 and 7C9) could reacted with fragments (F11, F9 and F3) containing the six amino acids V(2)ENAEK(7), but not reacted with the fragments with the deletion of any one of the six amino acids (F10, F7 and F8). Meanwhile, those purified truncated fragment proteins were used as the antigens in ELISA to detect the levels of those McAbs. The results showed that the OD 450 values of McAbs (6E11, 7A7 and 7C9) in F1, F3, F9 and F11 groups were significantly higher than those in F6, F7, F8 and F10 (p < 0.01) ( Figure 4A ). cache = ./cache/cord-303494-tofch4j7.txt txt = ./txt/cord-303494-tofch4j7.txt === reduce.pl bib === id = cord-309043-dlmx12vt author = von Brunn, Albrecht title = Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome date = 2007-05-23 pages = extension = .txt mime = text/plain words = 6706 sentences = 341 flesch = 52 summary = The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. There are reports that a number of MHV and SARS-CoV replicase proteins colocalize and eventually interact in cytoplasmic membrane bound complexes, in which viral RNA synthesis occurs [18, 19] . We therefore cloned the SARS-CoV ORFeome by recombinatorial cloning (GATEWAY technology) and performed a genome-wide analysis for viral protein interactions by yeast-two-hybrid (Y2H) matrix screen. To systematically study the subcellular localization of viral proteins within eukaryotic HeLa cells the SARS-CoV ORFs were transfected in eukaryotic vectors with either N-or C-terminal Flag tags and detected with an anti-Flag antibody. In this study we report the cloning of the complete ORFeome of SARS-CoV and the results of a matrix-based yeast two-hybrid screen of pairwise viral protein-protein interactions. cache = ./cache/cord-309043-dlmx12vt.txt txt = ./txt/cord-309043-dlmx12vt.txt === reduce.pl bib === id = cord-296347-fanlvxqs author = Loureiro, Joana title = Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions date = 2006-12-02 pages = extension = .txt mime = text/plain words = 28921 sentences = 1425 flesch = 45 summary = We discuss the many human cytomegalovirus (HCMV)-encoded immunomodulatory genes that interfere with antigen presentation (immunoevasins) and focus on the HCMV immunoevasins US2 and US11, which induce the degradation of class I MHC heavy chains by the proteasome by catalyzing their export from the endoplasmic reticulum (ER)-membrane into the cytosol, a process termed ER dislocation. One theme that arises from the characterization of this process over the 10 years that have passed since its discovery is that HC dislocation is unique in many respects: HC molecules do not meet the requirement of being either misfolded or misassembled, yet their dislocation takes place by virtue of the presence of US2 or US11; the speed of HC degradation is unrivaled by that of any other ER-associated degradation substrates: HC half-life is reduced from hours to a mere 2-5 min in cells infected by HCMV or in ce lls expressin g either US2 or US11 ( Wiertz et al ., 1996a ,b) ; both US2 and US11 have stringent requirements in terms of which HLA alleles (Barel et al., 2003 (Barel et al., , 2006 Machold et al., 1997) or assembly, folding and ubiquitination status of the class I MHC complex (Blom et al., 2004; Furman et al., 2003; Gewurz et al., 2001) either viral protein is able to target for dislocation and proteasomal destruction. cache = ./cache/cord-296347-fanlvxqs.txt txt = ./txt/cord-296347-fanlvxqs.txt === reduce.pl bib === id = cord-031907-ilhr3iu5 author = nan title = ISEV2020 Abstract Book date = 2020-07-15 pages = extension = .txt mime = text/plain words = 200999 sentences = 11528 flesch = 44 summary = L.M., and the National Institutes of Health (R35GM119623) to T.R.G. The addition of a size exclusion chromatography step to various urinary extracellular vesicle concentrating methods reveals differences in the small RNA profile Introduction: Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases, however non-vesicular RNA (e.g. associated with proteins) is also present within urine. We then evaluated efficiency of heart targeting for eAAV9 or eAAV6 and standard AAV9 or AAV6 encoding for EGFP, mCherry or firefly luciferase in different human cell lines in vitro, in black mouse and in passive immunity nude mouse model in vivo using flow cytometry, confocal microscopy, Langendorff perfusion system and Methods: HLHS patients (n = 3) after Glenn procedure and swine (n = 3) after PAB were given RV injections of allogeneic/xenogeneic MSCs. Donor-specific, HLA-I+, exosomes were isolated from plasma. cache = ./cache/cord-031907-ilhr3iu5.txt txt = ./txt/cord-031907-ilhr3iu5.txt === reduce.pl bib === id = cord-308043-h0knm8y4 author = Hussey, Séamus title = Autophagy as an emerging dimension to adaptive and innate immunity date = 2009-08-31 pages = extension = .txt mime = text/plain words = 6905 sentences = 378 flesch = 37 summary = These lines of evidence suggest a more elaborate TLR control of autophagy whereby TLR-adapter molecules interact with proteins from the autophagic pathway rather than by simply activating the classic hierarchical signaling cascades described heretofore. The authors demonstrated that the Atg5-Atg12 conjugate negatively regulates the antiviral immune response by interacting with the RIG-I-like receptor (s protein retinoic acid-inducible gene I (RIG-I) and IFN-␤ promoter stimulator 1 (IPS-1) thus, implying autophagy contributes to viral replication. In another study, the same group demonstrated that the fusion of influenza matrix protein 1 (MP1) with Atg8/LC3 drives this molecule to autophagosomes in different cell types and enhances recognition by antigen specific CD4+ T cells [117] . Accordingly, Atg6 silencing dampened this process, while rapamycin treatment enhanced priming of 85B-specific CD4 + T cells, strongly suggesting a role for autophagy in MHC class II presentation of antigens of bacterial origin. cache = ./cache/cord-308043-h0knm8y4.txt txt = ./txt/cord-308043-h0knm8y4.txt === reduce.pl bib === id = cord-308641-vqiipbo8 author = Jankauskaitė, Justina title = SKEMPI 2.0: an updated benchmark of changes in protein–protein binding energy, kinetics and thermodynamics upon mutation date = 2019-02-01 pages = extension = .txt mime = text/plain words = 5458 sentences = 232 flesch = 47 summary = Once the checks are passed, the data is collected, including the PDB file, the chains of the interacting subunits, the mutation, the wild-type and mutant affinities (K D , M), the reference, the names of the proteins, the temperature at which the experiment is performed (T, K), the experimental method used (an extension of the category scheme of Geng et al., 2016) , notes on the entry and, when available, the association rate (k on ; M À1 s À1 ), dissociation rate (k off ; s À1 ), enthalpy (DH; kcal:mol À1 ) and entropy (DS; cal:mol À1 :K À1 ). cache = ./cache/cord-308641-vqiipbo8.txt txt = ./txt/cord-308641-vqiipbo8.txt === reduce.pl bib === id = cord-298369-66ifwtlp author = Smith, Sherri A. title = Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein date = 2018-12-28 pages = extension = .txt mime = text/plain words = 10621 sentences = 491 flesch = 46 summary = The importance of plasma protein binding primarily resides in its impact on pharmacokinetic properties such as clearance (CL) and volume of distribution (V ss ), with serum albumin, lipoproteins and alpha-1 acid glycoprotein (AAG) being the major proteins involved in sequestering drugs in plasma (1) . While AAG represents a relatively small portion (~1-3%) of the total plasma proteins, compared to~60% composition of albumin, it can play a significant role in drug binding and pharmacokinetics (PK) (43) . Since AAG levels increase in most disease states (46) , drugs with a high affinity may demonstrate higher binding (lower fraction unbound, f u ) and altered PK properties (e.g. lower total CL), lower V ss . Effect of the plasticizer DEHP in blood collection bags on human plasma fraction unbound determination for Alpha-1-Acid Glycoprotein (AAG) binding drugs cache = ./cache/cord-298369-66ifwtlp.txt txt = ./txt/cord-298369-66ifwtlp.txt === reduce.pl bib === id = cord-307811-6e3j0pn7 author = Hao, Wei title = Binding of the SARS-CoV-2 Spike Protein to Glycans date = 2020-07-02 pages = extension = .txt mime = text/plain words = 5665 sentences = 299 flesch = 54 summary = Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. Previous studies of many other viruses suggested that SARS-CoV-2 S protein may use other molecules on host cell surface as attachment factors to facilitate binding to the high-affinity receptor ACE2. 36 A recent study suggested that HS may bind to the receptor binding domain (RBD, the C-terminal region of the S1 subunit, Fig. 2 ) of the SARS-CoV-2 spike protein and change its conformation. 38 In this study, we systematically examined and compared the binding of the SARS-CoV-2 S protein subunits, full-length molecule and its trimer to different HS using microarray experiments (Fig. 2) . In addition to binding protein-based receptors, many viruses can interact with cell surface glycans, including GAGs and sialic acid-containing oligosaccharides. cache = ./cache/cord-307811-6e3j0pn7.txt txt = ./txt/cord-307811-6e3j0pn7.txt === reduce.pl bib === id = cord-306111-wn1gxhk9 author = Dommett, R. M. title = Mannose‐binding lectin in innate immunity: past, present and future date = 2006-09-01 pages = extension = .txt mime = text/plain words = 9061 sentences = 436 flesch = 43 summary = Third MBL mutation in codon 52 (variant D) described (52) 1995 Polymorphisms found in promoter region of MBL gene (55) 1997 Second MASP found to activate complement (20) MBL mutations are an important risk factor for infections in children (132) 1998 Reconstitution of opsonizing activity by infusion of purified MBL into MBL-deficient humans (112) 1999 Truncated form of MASP-2 -MAp19 (21) 2000 Complement-activating complex of ficolins and MASP (133) MBL shown to bind to clinically relevant organisms (15) Structural aspects of MBL cache = ./cache/cord-306111-wn1gxhk9.txt txt = ./txt/cord-306111-wn1gxhk9.txt === reduce.pl bib === id = cord-310847-63gh2tg4 author = Uversky, Vladimir N title = The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins date = 2013-04-01 pages = extension = .txt mime = text/plain words = 19431 sentences = 1043 flesch = 50 summary = 5, 10, 46 In fact, in comparison with ordered proteins, IDPs/IDPRs are characterized by noticeable biases in their amino acid compositions, 5, 8, 10, [46] [47] [48] containing less of so-called "order-promoting" residues (cysteine, tryptophan, isoleucine, tyrosine, phenylalanine, leucine, histidine, valine, asparagines and methionine, which are mostly hydrophobic residues which are commonly found within the hydrophobic cores of foldable proteins) and more of "disorder-promoting" residues (lysine, glutamine, serine, glutamic acid and proline, which are mostly polar and charged residues, which are typically located at the surface of foldable proteins) (Fig. 1A) . Glutamic acid is an important functional residue of ordered proteins, where it can be involved in the formation of specific electrostatic valves inside the pores of ion channels, or can play unique catalytic roles in the active sites cache = ./cache/cord-310847-63gh2tg4.txt txt = ./txt/cord-310847-63gh2tg4.txt === reduce.pl bib === id = cord-306733-df36w6l7 author = Rosales-Mendoza, Sergio title = What Does Plant-Based Vaccine Technology Offer to the Fight against COVID-19? date = 2020-04-14 pages = extension = .txt mime = text/plain words = 8591 sentences = 420 flesch = 39 summary = Transient nuclear genome transformation Rapid production; high productivity; implemented at the industrial level Seed bank cannot be generated; requires purification of the antigen to eliminate toxic compounds from the host and ag-robacteria residues S protein; multiepitope vaccines A chimeric protein of GFP and amino acids 1-658 of the SARS-CoV-1 S protein (S1:GFP) was transiently expressed in tobacco leaves and stably transformed in tobacco and lettuce. No immunization assays were performed The SARS-CoV-1 N protein was transiently expressed in Nicotiana benthamiana, which induced in mice high levels of IgG1 and IgG2a and up regulation of IFN-γ and IL-10 in splenocytes. The precedents of SARS-CoV-1 and MERS antigens expressed in recombinant systems leading to the formation of VLPs constitute important guides for the topic of COVID-19 vaccine development. Thus, VLPs based on the main SARS-CoV-2 structural proteins is an attractive approach for vaccine development against coronavirus infections. cache = ./cache/cord-306733-df36w6l7.txt txt = ./txt/cord-306733-df36w6l7.txt === reduce.pl bib === id = cord-307227-x6xketcn author = Martin, William R. title = Repurposing of FDA-Approved Toremifene to Treat COVID-19 by Blocking the Spike Glycoprotein and NSP14 of SARS-CoV-2 date = 2020-09-10 pages = extension = .txt mime = text/plain words = 3999 sentences = 219 flesch = 52 summary = Here, we combine homology modeling, molecular docking, molecular dynamics simulation, and binding affinity calculations to determine potential targets for toremifene, a selective estrogen receptor modulator which we have previously identified as a SARS-CoV-2 inhibitor. These results suggest potential structural mechanisms for toremifene by blocking the spike protein and NSP14 of SARS-CoV-2, offering a drug candidate for COVID-19. 2, 3 In our initial network-based drug repurposing study, 4 we identified toremifene, another selective estrogen receptor modulator (SERM), as a strong candidate for the potential treatment of COVID-19. A drug repurposing study for SARS-CoV-1 5 indicated a low 50% effective concentration (EC 50 ) for toremifene, and noted that estrogen signaling may not be involved in the inhibitory pathway, similar to that of inhibition of Ebola. Future work will be needed to confirm these results; optimally, the determination of a cocrystal structure with Journal of Proteome Research pubs.acs.org/jpr Article NSP14 and/or the spike glycoprotein from SARS-CoV-2 with toremifene would be solved. cache = ./cache/cord-307227-x6xketcn.txt txt = ./txt/cord-307227-x6xketcn.txt === reduce.pl bib === id = cord-306624-1mjmttec author = Wodrich, Harald title = A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry date = 2010-03-19 pages = extension = .txt mime = text/plain words = 11594 sentences = 666 flesch = 53 summary = We show that the PPxY motif in protein VI is involved in its efficient microtubule-mediated transport and mutating it in the virus alters the intracellular targeting of Ads towards the MTOC region concomitant with a post-entry block in viral infectivity. To identify possible trafficking determinants, we analyzed the sequences of protein VI from several Ad serotypes and identified a highly conserved ubiquitin-ligase interacting motif present in PPxY-type viral late domains (PPxY, Figure S2 ). To determine whether the M1 mutation influences Ad cell entry, we performed a fluorescent focus forming assay and stained cells at 8, 12 and 24 h post-infection for expression of the E2A protein, which marks the appearance of viral replication centers ( Figure 2D and data not shown). In addition to the increase of protein VI capsid association, Ad5-VI-M1 appeared to be more evenly distributed throughout the cell and did not efficiently accumulate at the MTOC region ( Figure 3B , images to the left). cache = ./cache/cord-306624-1mjmttec.txt txt = ./txt/cord-306624-1mjmttec.txt === reduce.pl bib === id = cord-304607-td0776wj author = Paszkiewicz, Konrad H. title = Omics, Bioinformatics, and Infectious Disease Research date = 2010-12-24 pages = extension = .txt mime = text/plain words = 7022 sentences = 367 flesch = 46 summary = This chapter discusses the current state of play of bioinformatics related to genomics and transcriptomics, briefs metagenomics that finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms. Bioinformatics plays a key role at several steps in genomics, comparative genomics, and functional genomics: sequence alignment, assembly, identification of single nucleotide polymorphisms (SNP), gene prediction, quantitative analysis of transcription data, etc. The term "metagenomics" was originally used to describe the sequencing of genomes of uncultured microorganisms in order to explore their abilities to produce natural products (Handelsman et al., 1998 , Rondon et al., 2000 and subsequently resulted in novel insights into the ecology and evolution of microorganisms on a scale not imagined possible before (see Cardenas and Tiedje, 2008; Hugenholtz and Tyson, 2008 for an overview). However, metagenomics now finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms from, for example, patient material that could lead to the identification of the cause of disease. cache = ./cache/cord-304607-td0776wj.txt txt = ./txt/cord-304607-td0776wj.txt === reduce.pl bib === id = cord-310909-nc82a70n author = Qiu, Maofeng title = Antibody responses to individual proteins of SARS coronavirus and their neutralization activities date = 2005-04-13 pages = extension = .txt mime = text/plain words = 4520 sentences = 196 flesch = 48 summary = In this study, 13 recombinant proteins associated with four structural proteins (S, E, M and N) and five putative uncharacterized proteins (3a, 3b, 6, 7a and 9b) of the SARS-CoV were prepared and used for screening and monitoring their specific IgG antibodies in SARS patient sera by protein microarray. In the present study, to understand the profile of antibodies to individual proteins of the SARS-CoV, 13 recombinant proteins associated with four structural proteins (S, E, M and N) and five putative uncharacterized proteins (3a, 3b, 6, 7a and 9b) of this virus were prepared and used to screen and monitor their specific IgG antibodies in SARS patient sera using protein microarray, and the rabbit antisera to recombi-nant proteins S3 (aa 241-591), N (full length), 3a (aa 125-274) and 9b (full length) were prepared and used to investigate their neutralizing activity to the SARS-CoV infection in Vero E6 cells. cache = ./cache/cord-310909-nc82a70n.txt txt = ./txt/cord-310909-nc82a70n.txt === reduce.pl bib === id = cord-300429-b0zev8zb author = Sobocińska, Justyna title = Protein Palmitoylation and Its Role in Bacterial and Viral Infections date = 2018-01-19 pages = extension = .txt mime = text/plain words = 13428 sentences = 587 flesch = 40 summary = We highlight recent data on protein S-palmitoylation in pathogens and their hosts obtained owing to the development of methods based on click chemistry and acyl-biotin exchange allowing proteomic analysis of protein lipidation. Given the large variety of chemical reporters preferentially mimicking distinct fatty acids, recent years have witnessed a plethora of chemistry-based proteomic studies not only on palmitoylated but also myristoylated proteins and proteins bearing the GPI anchor, including those of pathogens and immune cells (10, 14, 85, 86, 114) The aBe Method Reveals Protein The envelope is rich in transmembrane, often S-palmitoylated, glycoproteins called spikes, which can bind to cognate receptors on the host cell plasma membrane triggering endocytosis of the virion, mediate subsequent fusion of the viral and cellular membranes allowing entry of the viral genome to the cytoplasm, and are also involved in the budding of newly formed virus particles from the cell. cache = ./cache/cord-300429-b0zev8zb.txt txt = ./txt/cord-300429-b0zev8zb.txt === reduce.pl bib === id = cord-306261-yc2y2xak author = van Tricht, Ewoud title = Fast, selective and quantitative protein profiling of adenovirus-vector based vaccines by ultra-performance liquid chromatography date = 2018-12-28 pages = extension = .txt mime = text/plain words = 5810 sentences = 275 flesch = 47 summary = The new RP-UPLC method was successfully validated for protein profiling and relative quantification of proteins in vaccine products based on adenovirus vector types 26 and 35. By calculating the relative peak areas of all peaks in the chromatogram and identifying new peaks in the chromatogram, the method also allows the detections of degradation products in the sample Additional requirements for the method development were: a chromatographic run time of less than 30 min, baseline separation of all relevant adenovirus proteins allowing for their quantification, and an increased method robustness. The linear gradient with three slopes was replaced by a single-slope linear gradient to improve elution reproducibility and the flow rate was increased The critical method parameters of the RP-UPLC method were studied in a screening design of experiments to assess their impact on the method's run time and the resolution between the adenovirus proteins.: The following conditions were evaluated: gradient start composition (0-20% solvent B), gradient end composition (45-65% solvent B), gradient run time (17-25 min), TFA concentration (0.04-0.12%), and column temperature (40-70 • C). cache = ./cache/cord-306261-yc2y2xak.txt txt = ./txt/cord-306261-yc2y2xak.txt === reduce.pl bib === id = cord-303555-mwu72q7w author = Dent, Paul title = Cell Signaling and Translational Developmental Therapeutics date = 2020-10-06 pages = extension = .txt mime = text/plain words = 8877 sentences = 556 flesch = 49 summary = Thus, by the mid-to late-1980s a large body of literature existed which argued that signal transduction pathways consisted of a receptor linked to a large GTP-binding protein which in turn regulated an enzyme that generated "second messengers;" the second messengers would then diffuse throughout the cytosol activating cellular processes, predominantly for metabolism. For the EGFR and other subsequently discovered membrane associated tyrosine kinases, e.g. the non-receptor SCR family and the fibroblast growth factor receptor (FGFR) family, understanding how these enzymes signaled into the cell again initially rested on studies using traditional biochemical methods. [71] [72] [73] [74] [75] [76] Contemporaneously with these studies, researchers were determining how receptor tyrosine kinases regulated RAS family small GTP binding proteins, and other groups determining how RAS proteins signaled downstream off the plasma membrane and into the cytosol. cache = ./cache/cord-303555-mwu72q7w.txt txt = ./txt/cord-303555-mwu72q7w.txt === reduce.pl bib === id = cord-300884-rqfxe0x1 author = Zhang, Jianqiang title = Genomic characterization of equine coronavirus date = 2007-12-05 pages = extension = .txt mime = text/plain words = 6804 sentences = 378 flesch = 56 summary = Analysis of the sequence identified 11 open reading frames which encode two replicase polyproteins, five structural proteins (hemagglutinin esterase, spike, envelope, membrane, and nucleocapsid) and four accessory proteins (NS2, p4.7, p12.7, and I). In contrast to the replicase proteins which are directly translated from the genomic RNA, coronavirus structural and accessory proteins are expressed from a nested set of 3′ coterminal subgenomic (sg) mRNAs that also possess a common 5′ leader sequence derived from the 5′ end of the genome (Pasternak et al., 2006; Sawicki et al., 2007) . Following multiple alignments with the S proteins of other group 2a coronaviruses, a potential cleavage recognition sequence (RRQRR) was identified at residues 764-768 which would predict a cleavage between amino acids 768 and 769, separating the ECoV S protein into S1 and S2 subunits (Fig. 1) . cache = ./cache/cord-300884-rqfxe0x1.txt txt = ./txt/cord-300884-rqfxe0x1.txt === reduce.pl bib === id = cord-310947-aqau2n7q author = Pan, Ji'An title = Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication date = 2008-10-01 pages = extension = .txt mime = text/plain words = 6821 sentences = 302 flesch = 43 summary = In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. However, the viral protein interaction maps have been generated until now only for a limited number of viruses, including T7 bacteriophage [1] , vaccinia virus [2] , potato virus A [3] , pea seed-borne mosaic virus [3] , wheat steak mosaic virus [4] , hepatitis C virus [5, 6] , porcine teschovirus [7] , Kaposi sarcoma-associated herpesvirus [8] , and very recently severe acute respiratory syndrome coronavirus (SARS-CoV) [9, 10] . cache = ./cache/cord-310947-aqau2n7q.txt txt = ./txt/cord-310947-aqau2n7q.txt === reduce.pl bib === id = cord-301827-a7hnuxy5 author = Uversky, Vladimir N title = A decade and a half of protein intrinsic disorder: Biology still waits for physics date = 2013-04-29 pages = extension = .txt mime = text/plain words = 20971 sentences = 1059 flesch = 43 summary = 94 Therefore, the abundance and peculiarities of the charged residues distribution within the protein sequences might determine physical and biological properties of extended IDPs and IDPRs. Also, simple polymer physics-based reasoning can give reasonably well-justified explanation of the conformational behavior of extended IDPs. In general, the conformational behavior of IDPs is characterized by the low cooperativity (or the complete lack thereof) of the denaturant-induced unfolding, lack of the measurable excess heat absorption peak(s) characteristic for the melting of ordered proteins, "turned out" response to heat and changes in pH, and the ability to gain structure in the presence of various binding partners. 183 This analysis revealed that proteins involved in regulation and execution of PCD possess substantial amount of intrinsic disorder and IDPRs were implemented in a number of crucial functions, such as protein-protein interactions, interactions with other partners including nucleic acids and other ligands, were shown to be enriched in post-translational modification sites, and were characterized by specific evolutionary patterns. cache = ./cache/cord-301827-a7hnuxy5.txt txt = ./txt/cord-301827-a7hnuxy5.txt === reduce.pl bib === id = cord-314642-oobbdgzh author = Campbell, Allan title = The future of bacteriophage biology date = 2003 pages = extension = .txt mime = text/plain words = 5945 sentences = 308 flesch = 53 summary = Several molecules of λ-integrase form an assemblage (the INTASOME) that binds to a specific segment of phage DNA, recruits the bacterial insertion sites into the complex, then makes concerted single-strand cuts in the two DNAs. The strand cutting proceeds through the covalent joining of a 3′ phosphate to a tyrosine of the integrase protein. Further efforts in this direction are desirable, not just for their intrinsic interest but also as models for viruses that infect eukaryotic hosts; for example, it is well documented that members of the coronavirus group, which has attracted attention recently through the emergence of a deadly new human pathogen that causes severe acute respiratory syndrome (SARS), undergo frequent recombination in nature 10, 11 . cache = ./cache/cord-314642-oobbdgzh.txt txt = ./txt/cord-314642-oobbdgzh.txt === reduce.pl bib === id = cord-302490-em1tiz7s author = Cañadas, Olga title = Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis date = 2020-05-25 pages = extension = .txt mime = text/plain words = 16675 sentences = 733 flesch = 32 summary = To fulfill this crucial role, alveolar epithelial type II cells (AE2C) secrete pulmonary surfactant, a lipid-protein complex that forms a surface active film at the respiratory interface, allowing its stability and avoiding alveolar collapse during expiration [3, 4] . On the other hand, the structure of surfactant aggregates does not influence its uptake by AMs [169] , and although SP-D is able to bind to the surface of these cells to modulate inflammation, the homeostasis/immune roles of the protein seem to be independently regulated [94] . Surfactant proteins and lipids have been shown to provide immune protection against respiratory pathogens, both directly by limiting inflammation and promoting pathogen clearance, and indirectly by activating molecular and cellular mechanisms that contribute to restore lung homeostasis [15, [181] [182] [183] . Anionic pulmonary surfactant phospholipids inhibit inflammatory responses from alveolar macrophages and U937 cells by binding the lipopolysaccharide-interacting proteins CD14 and MD-2 cache = ./cache/cord-302490-em1tiz7s.txt txt = ./txt/cord-302490-em1tiz7s.txt === reduce.pl bib === id = cord-302514-rstvf3mc author = Abbas, Wasim title = The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections date = 2015-04-07 pages = extension = .txt mime = text/plain words = 5138 sentences = 283 flesch = 38 summary = Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer, and lung cancer. Overexpression of eEF1A2 protein up-regulates overall PI4K activity and cellular phosphatidylinositol 4-phosphate (PI4P) generation in human cells. In addition, high-resolution analysis of genomic aberration by metaphase and comparative genomic hybridization array identify the involvement of the 20q region, suggesting the potential role of eEF1A2 as a candidate tumor gene in lung cancer cell lines (41) . eEF1A2 interacts directly with Prx-1 and protects the cells from stress-induced apoptosis by the down-regulation of caspase-3 and caspase-8 activation parallel to increased expression of the pro-survival factor Akt (76, 77) . Elongation factor 1 alpha interacts with phospho-Akt in breast cancer cells and regulates their proliferation, survival and motility Expression profile of eukaryotic translation factors in human cancer tissues and cell lines cache = ./cache/cord-302514-rstvf3mc.txt txt = ./txt/cord-302514-rstvf3mc.txt === reduce.pl bib === id = cord-306904-8iteddug author = Uversky, Vladimir N title = Unreported intrinsic disorder in proteins: Building connections to the literature on IDPs date = 2014-12-12 pages = extension = .txt mime = text/plain words = 18422 sentences = 1012 flesch = 48 summary = 86 Figure 8C represents the results of the computational disorder analysis in human APC (UniProt ID: P04070) and shows that mentioned loops enriched in basic residues are predicted to be disordered or very flexible, thereby providing an interesting mechanistic plane for the molecular basis of APC recognition and binding of FVIII. 96 Figure 8E shows that although human PECAM-1 (UniProt ID: P16284) is predicted to be mostly ordered, the residues, phosphorylation of which is crucial for its function (Y 663 and Y 686 ), are located within the highly disordered C-terminal tail. 210 Figure 14C represents the results of the disorder analysis of human AMSH (UniProt ID: O95630) and shows that this protein contains a long IDPR (residues 90-250) thereby illustrating that the N-terminal part of the analyzed catalytic domain is predicted to be disordered. [222] [223] [224] Figure 14D shows that human Purb protein (UniProt ID: O35295) is predicted to possess significant amount of functionally important intrinsic disorder. cache = ./cache/cord-306904-8iteddug.txt txt = ./txt/cord-306904-8iteddug.txt === reduce.pl bib === id = cord-304306-rxjahqwh author = Vlachakis, Dimitrios title = Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic date = 2020-10-08 pages = extension = .txt mime = text/plain words = 8517 sentences = 459 flesch = 48 summary = The currently available antiviral option for hospitalized patients is remdesivir, which may inhibit the replication process by targeting the RdRp. Previously proposed treatments for hospitalized patients included hydroxychloroquine, which thought to disrupt virus endocytosis, and lopinavir/ritonavir, which thought to inhibit SARs-CoV-2 main protease (Astuti and Ysrafil, 2020; Magro, 2020) . Silibilin is predicted to have a dual activity against SARS-CoV-2 infection; silibilin can potentially reduce viral replication activity by targeting NSP12 as a remdesivir-like inhibitor, and modulate inflammatory responses by direct inhibition of STAT3 (BoschBarrera et al., 2020) . A recombinant form of the human ACE2 protein was synthesized as a therapeutic treatment for COVID-19, functioning as a decoy for SARS-CoV-2 and essentially preventing the virus from binding to the cell surface ACE2 (Schuster et al., 2010) . Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response cache = ./cache/cord-304306-rxjahqwh.txt txt = ./txt/cord-304306-rxjahqwh.txt === reduce.pl bib === id = cord-315531-2gc2dc46 author = McGarvey, Peter B. title = Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets date = 2009-09-25 pages = extension = .txt mime = text/plain words = 7016 sentences = 335 flesch = 39 summary = (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. The centers have generated a heterogeneous set of experimental data using various technologies loosely defined as proteomic, but encompassing genomic, structural, immunology and protein interaction technologies, as well as more standard cell and molecular biology techniques used to validate potential targets identified via high-throughput methods. Here we describe in detail a protein-centric approach for systems integration of such a large and heterogeneous set of data from the NIAID Biodefense Proteomics program, and present scientific case studies to illustrate its application to facilitate the basic understanding of pathogen-host interactions and for the identification of potential candidates for therapeutic or diagnostic targets. cache = ./cache/cord-315531-2gc2dc46.txt txt = ./txt/cord-315531-2gc2dc46.txt === reduce.pl bib === id = cord-307731-a2fqmaly author = Vázquez, Javier title = Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches date = 2020-10-15 pages = extension = .txt mime = text/plain words = 11908 sentences = 594 flesch = 39 summary = In particular, the compounds obtained in the final rank order lead to meaningful increases in both performance and robustness over the single-modality approaches, but the results also demonstrate the sensitivity of the performance to the target structural details (i.e., the nature of the template ligand in measurements of molecular similarity and the reference protein pocket in docking studies) [67, 68] . In particular, the compounds obtained in the final rank order lead to meaningful increases in both performance and robustness over the single-modality approaches, but the results also demonstrate the sensitivity of the performance to the target structural details (i.e., the nature of the template ligand in measurements of molecular similarity and the reference protein pocket in docking studies) [67, 68] . cache = ./cache/cord-307731-a2fqmaly.txt txt = ./txt/cord-307731-a2fqmaly.txt === reduce.pl bib === id = cord-304953-ntg8w5k4 author = Modis, Yorgo title = Relating structure to evolution in class II viral membrane fusion proteins date = 2014-02-11 pages = extension = .txt mime = text/plain words = 3699 sentences = 177 flesch = 44 summary = The striking structural similarity between the flavivirus E proteins and RVFV G -which extends to the mode of dimerization even though E and Gc dimers form different types of icosahedral lattices -is strongly suggestive of a common evolutionary origin for certain envelope proteins within the Bunyaviridae and Flaviviridae families. The conservation of an a-helical coiled coil architecture in class I viral proteins and in the SNARE family of intracellular vesicle fusion proteins provides a compelling precedent for the evolutionary transfer of a structural membrane fusion fold between host and virus during evolution. . This study showed that the Gc envelope protein from Rift Valley fever virus (from the Bunyaviridae family) has a class II fold with striking resemblances to that of E from dengue and other flaviviruses, including a propensity to form head-to-tail dimers with a hydrophobic membrane anchor, or fusion loop buried at the dimer interface. cache = ./cache/cord-304953-ntg8w5k4.txt txt = ./txt/cord-304953-ntg8w5k4.txt === reduce.pl bib === id = cord-316745-n10ia3j3 author = Liu, HongDe title = A new approach to the prediction of transmembrane structures date = 2008-05-23 pages = extension = .txt mime = text/plain words = 1828 sentences = 133 flesch = 61 summary = In this paper, a new approach, maximum spectrum of continuous wavelet transform (MSCWT), is proposed to predict TMHs. The predictions for eight SARS-CoV membrane proteins indicate that MSCWT has the same capacity with software TMpred. In this paper, MSCWT was proposed to predict TMHs of membrane proteins. MSCWT of a signal could be obtained from the following steps: firstly, choose an appreciated mother wavelet and an appreciated scale range to perform CWT; then, detect and record the CWT maximum at every translation; finally, plot the recorded maximum value to its position (translation). Figure 1 shows the TMHs predicted by MSCWT and TMpred for SARS-CoV protein Orf9 and Orf14. MSCWT has the highest accuracy rate of membrane protein sequence (84.6%), while TMpred and DAS are 75.4% and 80.0%, respectively. In this paper, the proposed new method MSCWT shows a good efficiency in predicting the positions and amounts of TMHs of membrane protein. cache = ./cache/cord-316745-n10ia3j3.txt txt = ./txt/cord-316745-n10ia3j3.txt === reduce.pl bib === id = cord-309384-vlk8cebh author = Kolter, Thomas title = Ganglioside Biochemistry date = 2012-12-19 pages = extension = .txt mime = text/plain words = 16840 sentences = 960 flesch = 38 summary = A principal difference between ganglioside biosynthesis in the Golgi apparatus and degradation in the endolysosomal compartment is that during GSL formation, membranebound glycosyltransferases interact with their membranebound glycolipid substrates by diffusion within the twodimensional plane of the lipid bilayer. As glycosidase substrates, GSLs with four carbohydrate residues or less require the additional presence of small lipid binding glycoproteins, either the GM2 activator protein or one of the four saposins A-D. In vitro, in addition to enzymes and activator proteins, also an appropriate membrane-lipid composition of the ganglioside-containing membrane is required for degradation [222] . Due to the deficiency of two enzyme activities, β-hexosaminidases A and B, storage of negatively charged glycolipids characteristic for Tay-Sachs disease and, in addition, of uncharged substrates such as GA2 in the brain and globoside in visceral organs (Figure 16 ) is observed. cache = ./cache/cord-309384-vlk8cebh.txt txt = ./txt/cord-309384-vlk8cebh.txt === reduce.pl bib === id = cord-312332-rwmuucsp author = Dicker, Kate title = The importance of virion-incorporated cellular RNA-Binding Proteins in viral particle assembly and infectivity date = 2020-09-10 pages = extension = .txt mime = text/plain words = 9235 sentences = 480 flesch = 45 summary = title: The importance of virion-incorporated cellular RNA-Binding Proteins in viral particle assembly and infectivity Different proteomic studies have identified hundreds of cellular factors within the particles of several RNA viruses [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] , many of which are RBPs. Here, we discuss the 'knowns' and 'unknowns' of the roles that virion-incorporated cellular RBPs could play in the assembly of viral particles and the early steps of infection in the new host cell. Many ivRBPs such as annexins, heat shock family proteins (HSP), peptidylprolyl isomerase A (PPIA -also cyclophilin A), eukaryotic translation elongation factors (EEF), heterogeneous nuclear ribonucleoproteins (HNRNP) or poly(rC) binding protein 1 (PCBP1), have been linked to infection in multiple ways (Fig. S2) , and here we show that they are incorporated in the particles of several viruses (Table S1B) . cache = ./cache/cord-312332-rwmuucsp.txt txt = ./txt/cord-312332-rwmuucsp.txt === reduce.pl bib === id = cord-304616-k92fa15l author = Izes, Aaron M. title = Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats date = 2020-08-05 pages = extension = .txt mime = text/plain words = 4208 sentences = 234 flesch = 50 summary = title: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. Consequently, the aim of this study was two-fold: first, to develop and validate a high pressure liquid chromatography (HPLC) method to detect mefloquine in feline plasma, and second, to determine the in vitro plasma protein binding of mefloquine in both clinically normal and FIP-affected cats. Here, although a significant difference was found between the plasma protein binding of mefloquine in clinically normal and FIP-affected cats, due to the unknown biological variability of the assay, it is likely that this difference is equivocal. This study has validated an accurate and reliable assay to detect mefloquine in feline plasma and demonstrated that mefloquine is highly plasma protein bound in both clinically normal and FIP-affected cats. cache = ./cache/cord-304616-k92fa15l.txt txt = ./txt/cord-304616-k92fa15l.txt === reduce.pl bib === id = cord-319517-denczc6t author = Salipalli, Sandeep title = Recent advances in live cell imaging of hepatoma cells date = 2014-07-08 pages = extension = .txt mime = text/plain words = 9184 sentences = 433 flesch = 46 summary = This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. The success of live cell imaging relies on various factors including the specific imaging system, climate controlling devices for cultured cells under investigation, construction of recombinant plasmid DNA, transfer and expression of candidate genes and/or fluorescent proteins in mammalian cells. T4SS (Bartonella sp.) 60-70% 50% >70% >60% 50-60% [76] [77] [78] lipofection (1 μg) methods were used for transfection of plasmid encoding fluorescent protein (pEGFP and pEYFP) tagged to human and mouse ADRP genes in Huh-7 cells as to study the pathways of lipid droplet metabolism. cache = ./cache/cord-319517-denczc6t.txt txt = ./txt/cord-319517-denczc6t.txt === reduce.pl bib === id = cord-312996-qzu8pkyt author = Iles, R. K. title = A clinical MALDI-ToF Mass spectrometry assay for SARS-CoV-2: Rational design and multi-disciplinary team work. date = 2020-08-22 pages = extension = .txt mime = text/plain words = 6845 sentences = 375 flesch = 51 summary = Testing limitations, including reagent shortages, remain a bottleneck in the battle to curtail COVID-19 spread in even the wealthiest countries [1, 2] The development of new matrix assisted laser desorption time of flight mass spectrometry (MALDI-ToF MS) diagnostics for SARS-CoV-2 detection is driven by the need for greater diagnostic capacity and alternative applications to complement standard PCR and antibody based diagnostics. Consequently studies where swab samples have been split for simultaneous analysis by RT PCR detection systems of SARS-CoV-2 RNA and by MALDI-ToF mass spectrometry for viral proteins, are compromised [4] . virus grown in vitro and mass spectra of gargle/saliva spiked with culture media from cells infected with SARS-CoV-2: S proteolytic fragments S1 and S2 were seen in all preparations and S2b only in serum free samples. These confirmed PCR-negative gargle samples were analysed by MALDI-ToF mass spectrometry 40 times; the measured peak intensities of which acted as comparative controls to the viral spiked saliva/gargle. cache = ./cache/cord-312996-qzu8pkyt.txt txt = ./txt/cord-312996-qzu8pkyt.txt === reduce.pl bib === id = cord-312741-0au4nctt author = Lin, Panpan title = Coronavirus in human diseases: Mechanisms and advances in clinical treatment date = 2020-10-01 pages = extension = .txt mime = text/plain words = 14665 sentences = 840 flesch = 42 summary = 160, 161 Once the PAMPs from invaded viruses are detected, RIG-I and MDA5 interact with the mitochondrial antiviral signaling protein (MAVs) that is a mitochondrial membrane-bound F I G U R E 2 Escape mechanisms of innate immune response of SARS-CoV and MERS-CoV adaptor molecule, followed by the activation of several kinase complexes and multiple subsequent transcription factors (IRF3, IRF7, and NF-κB). Antiviral peptides analogous derived from these regions exhibited inhibition to the spike protein-mediated cell-cell fusion and viral entry in viruses such as SARS-CoV, MERS-CoV, as well as HCoV-229E. Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein cache = ./cache/cord-312741-0au4nctt.txt txt = ./txt/cord-312741-0au4nctt.txt === reduce.pl bib === id = cord-312489-ywep0c08 author = Andoh, Kiyohiko title = Decreased neutralizing antigenicity in IBV S1 protein expressed from mammalian cells date = 2015-10-02 pages = extension = .txt mime = text/plain words = 5039 sentences = 246 flesch = 43 summary = We evaluated the antigenicity of recombinant infectious bronchitis virus (IBV) S1 protein expressed in mammalian cells. Native S1 ELISA detected similar titers in the sera of animals immunized with recombinant S1 protein compared to those in sera of chickens immunized with inactivated virus (Fig. 6b ) (Control experiments (data not shown) demonstrated that mock and unvaccinated control groups did not differ from each other in VN and ELISA tests of anti-S1 activity.) These results indicated that while recombinant S1 protein retained antigenicity (the ability to induce antibodies against S1 protein), the resulting antibodies was decreased its neutralizing activity, in contrast to those induced by inactivated virus. The S1 glycoprotein but not the N or M proteins of avian infectious bronchitis virus induces protection in vaccinated chickens Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus cache = ./cache/cord-312489-ywep0c08.txt txt = ./txt/cord-312489-ywep0c08.txt === reduce.pl bib === id = cord-316273-vo6j8zb0 author = Cosset, François-Loic title = Cell Entry of Enveloped Viruses date = 2011-02-08 pages = extension = .txt mime = text/plain words = 23421 sentences = 1013 flesch = 40 summary = On the one hand, they acquired a domain to bind to a specific cellular protein, named "receptor." On the other hand, they developed in a different manner, according to the genus of the virus, a function of fusion that allows the destabilization of the membrane and the opening of a pore through which the genetic material will enter the cell. Thus, we need to distinguish cell surface molecules such as heparan sulfate proteoglycans, DC-SIGN, or integrins that can enhance infections by concentrating retroviruses onto cells (Bounou et al., 2002; Geijtenbeek et al., 2000; Jinno-Oue et al., 2001; Mondor et al., 1998; Pohlmann et al., 2001; Saphire et al., 2001) from authentic receptors that induce conformational changes in EnvGP that are a prerequisite for fusion of the viral and cellular membranes. cache = ./cache/cord-316273-vo6j8zb0.txt txt = ./txt/cord-316273-vo6j8zb0.txt === reduce.pl bib === id = cord-315984-5gbhobw8 author = Isaacson, Marisa K. title = Ubiquitination, Ubiquitin-like Modifiers, and Deubiquitination in Viral Infection date = 2009-06-18 pages = extension = .txt mime = text/plain words = 8898 sentences = 467 flesch = 44 summary = HPV infection also leads to degradation of the retinoblastoma protein pRb through the ubiquitin-proteasome pathway (reviewed in Mammas et al., 2008) , mediated via the HPV E7-protein-induced generation of an E3 ligase complex consisting of the Cullin2 Processed ubiquitin (Ub) or ubiquitin-like modifier (Ubl) is activated with ATP by an E1 ubiquitin-activating enzyme (1) and then transferred to an E2 ubiquitin-conjugating enzyme (2). Herpes simplex virus 1 (HSV-1) infected cell protein 0 (ICP0) is a E3 ubiquitin ligase that induces polyubiquitination and degradation of a variety of proteins, including the promyelocytic leukemia (PML) protein, Sp100 (another component of PML nuclear bodies) (Chelbi-Alix and de Boutell et al., 2002) , cyclin D3 (Van Sant et al., 2001; Hagglund et al., 2002) , p53, and the cellular deubiquitinating enzyme USP7. cache = ./cache/cord-315984-5gbhobw8.txt txt = ./txt/cord-315984-5gbhobw8.txt === reduce.pl bib === id = cord-313932-f0a1qh7p author = Chen, Peng title = Establishment and validation of a drug-target microarray for SARS-CoV-2 date = 2020-07-21 pages = extension = .txt mime = text/plain words = 2483 sentences = 148 flesch = 49 summary = Here, we constructed a COVID-19 protein microarray of potential therapy targets, which contains the main drug targets to the SARS-COV-2 virus and the anti-virus, anti-inflammatory cellar targets of the host. For protein target research of traditional Chinese medicine, it is usually carried out through network pharmacology and bioinformatics, for example, by obtaining the main active ingredients of LianhuaQingwen capsule, molecular docking method was used to predict the possible targets [11, 12] . The latest research showed EIF4E2 as an important host interaction protein with virus, potential to be a drug target for COVID-19 [24] . NFkB1-P50 protein is an important target of andrographolide, a traditional Chinese medicine product with immunoregulation function, and their binding site has been widely verified [26] (Figure 3A ). Here, we use the method of network pharmacology molecular docking to predict the binding ability of these two natural products to the protein targets. cache = ./cache/cord-313932-f0a1qh7p.txt txt = ./txt/cord-313932-f0a1qh7p.txt === reduce.pl bib === id = cord-318853-mxyxwkhx author = Sallie, Richard title = Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases date = 2005-08-22 pages = extension = .txt mime = text/plain words = 10541 sentences = 396 flesch = 25 summary = Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. Hence, as relative concentrations of wild-type and variant viral proteins vary, alteration of both processivity and fidelity of RNA pol results, permitting viruses to adaptively respond to environmental changes, including immune recognition and reaction to evolving cell receptors. As clear evidence exists for viral disruption of leptin function [106] and virus-associated weight gain in humans [107] and monkeys [108] , is it possible the global epidemics of type II diabetes mellitus, insulin resistance, hyperlipidaemia and obesity now prevalent [109] [110] [111] [112] [113] [114] [115] [116] , are just that; epidemics fundamentally caused by viruses that co-opt insulin or leptin or other associated receptors for cell access and generate protein quasispecies that disrupt receptor function? cache = ./cache/cord-318853-mxyxwkhx.txt txt = ./txt/cord-318853-mxyxwkhx.txt === reduce.pl bib === id = cord-313988-3xjnpkqp author = Ferraz, Rosa María title = Insertional protein engineering for analytical molecular sensing date = 2006-04-03 pages = extension = .txt mime = text/plain words = 3516 sentences = 147 flesch = 25 summary = In this context, insertional protein engineering offers the possibility to develop new devices, efficiently responding to ligand interaction by dramatic conformational changes, in which the specificity and magnitude of the sensing response can be adjusted up to a convenient level for specific analyte species. Among enzyme inhibitors and other few ligand species that activate allosteric biosensors, antibodies have been noted to be specially efficient allosteric effectors [36] and the use of antigenic peptides as receptors in only-protein biosensors would offer appealing tools for the fast molecular diagnosis of infectious diseases [39, 43] . For such a sensor being efficiently responsive, appropriated permissive sites need to be selected permitting proper receptor display and signal transduction, and the whole protein might require further engineering to gain specificity and response range. Among the diversity of sensing strategies based on insertional mutagenesis two protein platforms emerge as the most explored, namely cleavable sensors responding to proteases or their inhibitors, and allosteric, among whose most efficient effectors are antibodies. cache = ./cache/cord-313988-3xjnpkqp.txt txt = ./txt/cord-313988-3xjnpkqp.txt === reduce.pl bib === id = cord-319609-y0gdjn64 author = Van Duyne, Rachel title = The identification of unique serum proteins of HIV-1 latently infected long-term non-progressor patients date = 2010-07-06 pages = extension = .txt mime = text/plain words = 8544 sentences = 356 flesch = 47 summary = In particular, the analysis of HIV-1 infected serum is an attractive medium with which to identify altered protein expression due to the ease and non-invasive methods of collecting samples as well as the corresponding insight into the in vivo interaction of the virus with infected cells/tissue. We have analyzed and compared serum samples from HIV-1 infected subjects who are being treated using highly active antiretroviral therapy (HAART) to those who are latently infected but have not progressed to AIDS despite the absence of treatment, i.e. long term non-progressors (LTNPs). In order to gain insight into the reason why p16 INK4A may be present preferentially in the serum of LTNP patients, we treated latently infected HIV-1 cell lines (J1.1 and U1) with exogenous purified GST-p16 INK4A Figure 4A depicts an RT assay which measures the viral reverse transcriptase activity of infected cells and is an indicator of functional particle production. cache = ./cache/cord-319609-y0gdjn64.txt txt = ./txt/cord-319609-y0gdjn64.txt === reduce.pl bib === id = cord-318551-c1qr27lg author = Boguszewska‐Chachulska, Anna M. title = Rna Viruses Redirect Host Factors to Better Amplify Their Genome date = 2005-12-29 pages = extension = .txt mime = text/plain words = 10673 sentences = 511 flesch = 44 summary = (Adapted with permission from Pasternak et al., 2001.) Transcription of segmented (À) strand RNA viruses such as the Orthomyxoviridae, Arenaviridae, Bunyaviridae, and Tenuiviruses requires a primer to initiate synthesis of the mRNAs. This is achieved by cap-snatching in which the replicase complex, or a protein thereof, binds to the 5 0 region of cell mRNAs, cleaves off the cap together with generally 7-15 nucleotides from the 5 0 end of the cell mRNA, and uses this fragment as a primer to initiate synthesis of the viral mRNAs (Bouloy et al., 1978; Nguyen and Haenni, 2003) . (1996) PV, poliovirus; MHV, mouse hepatitis virus; WNV, West Nile virus; BVDV, bovine viral diarrhea virus; HPIV-3, human parainfluenza virus-3; IG (À), intergenic region in (À) RNA; UTR, untranslated region; Leader RNA (À), 3' end of (À) RNA; Leader RNA (þ), 5' end of (þ) RNA; HF, host factor; PCBP, poly(C)-binding protein; PABP, poly(A)-binding protein; hnRNP A1, heterogeneous nuclear ribonucleoprotein A1; PTB, polypyrimidine tract-binding protein; TIA-1, T-cell-activated intracellular antigen; TIAR, TIA-1-related; RHA, RNA helicase A; GAPDH, glyceraldehyde-3-phosphate dehydrogenase. cache = ./cache/cord-318551-c1qr27lg.txt txt = ./txt/cord-318551-c1qr27lg.txt === reduce.pl bib === id = cord-310680-klywz85w author = Li, Qihan title = The interaction of the SARS coronavirus non-structural protein 10 with the cellular oxido-reductase system causes an extensive cytopathic effect date = 2005-04-06 pages = extension = .txt mime = text/plain words = 4397 sentences = 210 flesch = 53 summary = The gene for the SARS-CoV non-structural protein 10, which is located in the open reading frame of pp1a/pp1ab gene, was synthesized and used to screen for the specific cellular gene coding for the protein interacting with this nsp10 protein in a human embryo lung cDNA library using a yeast trap method. The pathological analysis of the lung tissue from the deceased patients revealed severe Abbreviations: SARS-CoV, severe acute respiratory syndrome coronavirus; BTF3, basic transcription factor-3; ATF5, activation transcription factor-5; NADH, nicotinamide adenine dinucleotide dehydrogenase; FBS, fetal bovine serum; DMEM, double minimal essential media; QDO, quartdrop-out; NC, nitrocellulose; HE, hematoxyline and eosin method; GFP, green fluorescence protein; GST, glutathione S-transferase * Corresponding author. To further investigate the contribution of this interaction to the cytopathic effect of SARS-CoV, a detection series of mitochondrial function and the activity of the oxido-reductase system in the human embryo lung fibroblast transfected with the nsp10 gene was performed. cache = ./cache/cord-310680-klywz85w.txt txt = ./txt/cord-310680-klywz85w.txt === reduce.pl bib === id = cord-314751-i9rxesrg author = Oh, Jongsuk title = Immunogenicity and protective efficacy of recombinant S1 domain of the porcine epidemic diarrhea virus spike protein date = 2014-07-10 pages = extension = .txt mime = text/plain words = 6006 sentences = 242 flesch = 44 summary = In this study, a codon-optimized PEDV S1 gene containing amino acid residues 25–738 was synthesized based on a multiple alignment of the S amino acid sequences of PEDV field isolates and used to establish a stable porcine cell line constitutively expressing the PEDV S1 protein. In the present study, therefore, we first synthesized a full-length, codon-optimized PEDV S1 gene and then generated a stable porcine-origin cell line constitutively expressing the recombinant S1 protein. These results were coincident with the rabbit study described above, since the rabbit antisera generated by immunization with the recombinant S1 protein also contained low levels of neutralizing antibodies to the heterologous PEDV vaccine strain. In the present study, the first aim was to stably express the full-length, codon-optimized S1 gene of PEDV in porcine-origin cells and to evaluate the immunogenicity and efficacy of the recombinant S1 protein. cache = ./cache/cord-314751-i9rxesrg.txt txt = ./txt/cord-314751-i9rxesrg.txt === reduce.pl bib === id = cord-318749-k91oku7h author = Dong, Hui-Jun title = Selective regulation in ribosome biogenesis and protein production for efficient viral translation date = 2020-10-29 pages = extension = .txt mime = text/plain words = 7265 sentences = 384 flesch = 38 summary = Recently reported studies have demonstrated that ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs) act as multifaceted regulators in selective translation of viral transcripts. Similarly, ribosomes are required for the protein synthesis of host cells and viruses, but the biogenesis factor RBFs can also impact the proliferation of virus and cell-intrinsic immune responses. The multifunctional nucleolar phosphoprotein nucleophosmin (NPM) plays a lead role in ribosome biogenesis to stimulate RNA Pol I-dependent transcription (Li and Hann 2013) and regulates SARS-CoV, IBV, HIV-1, HCV Recruited by viral proteins to facilitate viral replication Chen et al. RPS25 deletion in yeast or mammalian cells has minimal effects on cellular protein synthesis, which implies that this ribosomal protein may be selectively required for viral IRES-mediated translation (Jack et al. Conservation of multifunctional ribosomal protein metallopanstimulin-1 (RPS27) through complex evolution demonstrates its key role in growth regulation in Archaea, eukaryotic cells, DNA repair, translation and viral replication cache = ./cache/cord-318749-k91oku7h.txt txt = ./txt/cord-318749-k91oku7h.txt === reduce.pl bib === id = cord-314746-1o0rf0ii author = Bergasa-Caceres, Fernando title = Interdiction of Protein Folding for Therapeutic Drug Development in SARS CoV-2 date = 2020-08-10 pages = extension = .txt mime = text/plain words = 5038 sentences = 304 flesch = 56 summary = [Image: see text] In this article, we predict the folding initiation events of the ribose phosphatase domain of protein Nsp3 and the receptor binding domain of the spike protein from the severe acute respiratory syndrome (SARS) coronavirus-2. The identification of the primary contacts along the folding pathway of viral proteins constitutes an important result for at least two reasons: (a) the sequences of the specific segments involved in the primary contacts provide a template to specify candidate peptide drugs of inhibitory effect with the maximum possible contact affinity to compete with the natural folding mechanism; and (b) it provides insight for further investigation into the subsequent folding steps leading to a fully functional viral protein, potentially providing for additional FITRs. The fact that the primary contact is defined by the interaction between two well defined amino acid sequences suggests that a strategy to develop FITR-based therapeutic drugs could be one utilizing trial peptide drugs as suggested above. cache = ./cache/cord-314746-1o0rf0ii.txt txt = ./txt/cord-314746-1o0rf0ii.txt === reduce.pl bib === id = cord-317675-s1ac5vcx author = de Marco, Ario title = Strategies for successful recombinant expression of disulfide bond-dependent proteins in Escherichia coli date = 2009-05-14 pages = extension = .txt mime = text/plain words = 11534 sentences = 524 flesch = 31 summary = The cytoplasmic accumulation of thioredoxin as a consequence of its recombinant overexpression in wild type bacteria was proposed for increasing the yields of coexpressed eukaryotic proteins without disulfide bonds in their native structure [191] . Fusions between recombinant scFvs and thioredoxin 1 expressed in trxB -, gorbacteria resulted in increased cytoplasmic yields [196] , correct folding of a scFv against the c-Met receptor [188] , and of the first domain of the multiple Kazal-type inhibitor LEKTI, a polypeptide that contains two disulfide bridges in its native structure [197] . In the case of a serpin domain, AD494 cells did not improve the total amount of soluble recombinant protein accumulated in the cytoplasm with respect to wild type bacteria, but it was correctly folded and active, whilst the protein expressed in the control cells did not form the essential disulfide bonds [210] . cache = ./cache/cord-317675-s1ac5vcx.txt txt = ./txt/cord-317675-s1ac5vcx.txt === reduce.pl bib === id = cord-314039-qkrmxvaj author = Houdebine, Louis-Marie title = Production of pharmaceutical proteins by transgenic animals date = 2008-02-19 pages = extension = .txt mime = text/plain words = 4773 sentences = 278 flesch = 47 summary = Interestingly, genetically modified yeast expressing foreign genes coding for enzymes responsible for glycosylation proved able to secrete substantial amounts of recombinant proteins having carbohydrates almost similar to those found in human proteins [1] . Transgenic animals offer particularly attractive possibilities to prepare recombinant pharmaceutical proteins. Ruminants are potentially the most appropriate species to produce large amount of proteins but they need cloning or lentiviral vectors to integrate foreign genes, their reproduction is relatively slow, they do not glycosylate proteins as well as rabbits and pigs and they are sensitive to prion diseases (Tables 3 and 4) . The recombinant protein ATryn (human antithrombinIII) produced in goat milk contains less sialic acid than its native counterpart is a case in point [29] . The two major animal systems to produce pharmaceutical proteins in milk and egg white have recently been technically improved and their use as an essential source of new medicaments has become very likely. cache = ./cache/cord-314039-qkrmxvaj.txt txt = ./txt/cord-314039-qkrmxvaj.txt === reduce.pl bib === id = cord-313694-p2sgaypq author = West, Christopher M. title = Current ideas on the significance of protein glycosylation date = 1986 pages = extension = .txt mime = text/plain words = 10897 sentences = 534 flesch = 36 summary = The alternate view is that carbohydrate structures participate in numerous specific interactions with discrete protein receptors, and that these interactions lead to predictable modifications in the localization or activity of the glycoprotein. The notion of a 'non-specific' role for carbohydrate has received perhaps its strongest support from studies on cells whose glycosylation processes have been globally altered by mutation or drugs. Consideration of the possible role of carbohydrate in other molecular associations with the plasma membrane will be considered below in sections on hormone-receptor interactions and cellsubstratum (e.g., extracellular matrix) and cell-cell adhesion. Considerable evidence has been adduced that various parasites such as viruses, bacteria, protozoa, etc., possess carbohydrate binding proteins which can interact with sugar structures on the surfaces of cells with which the parasites associate (167, 168, (116) (117) (118) (119) . In any case, antibodies and lectins may model potential receptors in cells which might specifically recognize carbohydrate-associated structures. cache = ./cache/cord-313694-p2sgaypq.txt txt = ./txt/cord-313694-p2sgaypq.txt === reduce.pl bib === id = cord-316983-h4mtpcyc author = Mathé-Hubert, Hugo title = Comparative venomics of Psyttalia lounsburyi and P. concolor, two olive fruit fly parasitoids: a hypothetical role for a GH1 β-glucosidase date = 2016-10-25 pages = extension = .txt mime = text/plain words = 8294 sentences = 425 flesch = 51 summary = We have identified here the main venom proteins of two braconid wasps, Psyttalia lounsburyi (two strains from South Africa and Kenya) and P. To assess whether this variation between two figitid species that differ in their host range similarly exists in other parasitoid taxa, we compared here the venom composition of two braconid wasps, Psyttalia lounsburyi and P. This resulted in a total of 32 and 30 putative venom proteins for Pl and Pc respectively (Tables 1 and 2), whose relative abundance was compared using (i) the RPKM normalized number of Illumina reads from Pl and Pc venom apparatus, mapped to the assembled transcriptomes and (ii) the number of peptides matches in Mascot searches. Interestingly, most of the proteins identified in the proteomics of the reservoir (detection of the most abundant putative venom proteins only, data not shown), such as actin or paramyosin, had a predicted muscular function, as expected from microscopy observations (see above; Fig. 1 ). cache = ./cache/cord-316983-h4mtpcyc.txt txt = ./txt/cord-316983-h4mtpcyc.txt === reduce.pl bib === id = cord-319884-d8n0aokl author = Natesan, Mohan title = Protein Microarrays and Biomarkers of Infectious Disease date = 2010-12-16 pages = extension = .txt mime = text/plain words = 7088 sentences = 359 flesch = 36 summary = Fluorescencebased detection of protein interactions is similar to gene array methods, and data analysis often employs approaches previously developed for genome and transcription studies. A standard assay for measuring antibody interactions with proteins of the vaccinia proteome microarray was first developed with a pool of therapeutic human sera collected from vaccinia-immune individuals (VIg) and this data was compared to results obtained from individuals vaccinated against smallpox using Dryvax. Results from this study suggested that antibodies from vaccination recognized a small number of proteins shared with pathogenic viral strains, while recovery from infection also involved humoral immunity to antigens uniquely recognized within the monkeypox virus proteome (unpublished data). For example, a protein array produced from the outer membrane proteins of Pseudomonas aeruginosa was constructed [38] to study the immune response in patients, and several antibody-binding antigens were identified by this group as potential diagnostic markers. cache = ./cache/cord-319884-d8n0aokl.txt txt = ./txt/cord-319884-d8n0aokl.txt === reduce.pl bib === id = cord-314567-purplsjn author = Fernández-Ponce, Cecilia title = Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells date = 2018-01-04 pages = extension = .txt mime = text/plain words = 7978 sentences = 382 flesch = 41 summary = HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. As studies using the whole virus do not allow for the elucidation of the specific molecular mechanisms in which each protein is implicated, in this work, we focused on a single viral protein, showing that in CD4 + T cells, HCV core protein mostly localizes in the nucleus and specifically in the nucleolus where it is greatly enriched. cache = ./cache/cord-314567-purplsjn.txt txt = ./txt/cord-314567-purplsjn.txt === reduce.pl bib === id = cord-319563-9lwr6k8p author = Aitekenov, Sultan title = Review: Detection and quantification of proteins in human urine date = 2020-10-14 pages = extension = .txt mime = text/plain words = 10099 sentences = 611 flesch = 40 summary = This review focuses on the instrumental quantification (electrophoresis, chromatography, immunoassays, mass spectrometry, fluorescence spectroscopy, the infrared spectroscopy, and Raman spectroscopy) of proteins (the most of all albumin) in human urine matrix. Among the reasons that make urine challenging for researchers to analyze are: urine matrix is complex, it consists of various inorganic and organic compounds, from low-molar mass molecules to polymers; urine could contain cells, such as blood cells, or bacteria, which changes the composition of urine in time rapidly; an analytical method for diagnosis of proteinuria should cover protein presence in urine in a wide range from 0.01 mg/ml to 10 mg/ml. focuses on urinary proteins as potential biomarkers for mainly urine diseases, and capillary electrophoresis coupled mass spectroscopy as an instrumental method [33] . In this review, we focused on instrumental determination of abundant proteins in urine by electrophoresis, chromatography, mass spectrometry, immunoassay, fluorescence, IR, and Raman spectroscopy. cache = ./cache/cord-319563-9lwr6k8p.txt txt = ./txt/cord-319563-9lwr6k8p.txt === reduce.pl bib === id = cord-319614-4qi59pbz author = Benej, Martin title = Quantitative Proteomics Reveal Peroxiredoxin Perturbation Upon Persistent Lymphocytic Choriomeningitis Virus Infection in Human Cells date = 2019-10-25 pages = extension = .txt mime = text/plain words = 8900 sentences = 479 flesch = 45 summary = Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. Increased levels of ROS were accompanied by changes in the pattern of telomere restriction fragments (TRFs) in infected cells and mediated activation of hypoxia-inducible transcription factor-1 (HIF-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. These data suggest that LCMV maintains its replication in persistently infected cells by regulating redox signaling through modulation of local levels of H 2 O 2 and subsequent activation of cellular processes that it uses for its own benefit. Notably, the treatment with antioxidants also resulted in reduced levels of viral NP in HeLa, as well as in A549 LCMV-infected cells, suggesting a link between ROS-dependent signaling and virus replication (Figures 7B,D and Supplementary Figure S2B ). cache = ./cache/cord-319614-4qi59pbz.txt txt = ./txt/cord-319614-4qi59pbz.txt === reduce.pl bib === id = cord-320015-lbr2q4qh author = Chinchar, V. Gregory title = The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date = 2011-10-20 pages = extension = .txt mime = text/plain words = 9130 sentences = 433 flesch = 43 summary = Additional IE and DE proteins include proteins that may play roles in blocking host immune responses such as a virus-encoded, CARD (caspase activation and recruitment domain) motif-containing protein (vCARD), β-hydroxysteroid dehydrogenase (βHSD), and a RNAse III-like protein, catalytic proteins involved in nucleic acid synthesis (Proliferating Cell Nuclear Antigen [PCNA], DNA methyltransferase [DMTase], the large and small subunits of the viral homolog of cellular RNA polymerase II [vPOL-IIα and -IIβ], transcription factor IIS), catalytic proteins that may act to increase dTTP pool sizes and influence host range (deoxyuridine triphosphatase [dUTPase], deoxynucleotide kinase, the large and small subunits of ribonucleotide reductase), and proteins non-essential for replication in vitro, but needed for growth in vivo (the 18K protein) [22] . Lastly, Sample and co-workers observed that KD of the 18K IE protein had no observable effect on viral gene expression or replication in vitro suggesting that, at least in fathead minnow cells, 18K was not required for the production of infectious virions. cache = ./cache/cord-320015-lbr2q4qh.txt txt = ./txt/cord-320015-lbr2q4qh.txt === reduce.pl bib === id = cord-321386-u1imic5l author = Li, Chun title = Protein Sequence Comparison and DNA-binding Protein Identification with Generalized PseAAC and Graphical Representation date = 2018-02-17 pages = extension = .txt mime = text/plain words = 5503 sentences = 311 flesch = 59 summary = METHODS: Based on two physicochemical properties of amino acids, a protein primary sequence was converted into a three-letter sequence, and then a graph without loops and multiple edges and its geometric line adjacency matrix were obtained. A generalized PseAAC (pseudo amino acid composition) model was thus constructed to characterize a protein sequence numerically. In addition, a generalized PseAAC based SVM (support vector machine) model was developed to identify DNA-binding proteins. Also, we develop a SVM (support vector machine) model using the generalized PseAAC to identify DNA-binding and non-binding proteins on three datasets. By combining these elements with the conventional amino acid composition (AAC), a dimensional feature vector can be constructed to numerically characterize a protein sequence: , By combining these elements with the frequencies of occurrence of 20 standard amino acids and their three representative letters, a generalized PseAAC model of a protein sequence was constructed. Numerical characterization of protein sequences based on the generalized Chou's pseudo amino acid composition cache = ./cache/cord-321386-u1imic5l.txt txt = ./txt/cord-321386-u1imic5l.txt === reduce.pl bib === id = cord-314321-klb8oe9q author = Chen, Serena H. title = Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets date = 2020-04-18 pages = extension = .txt mime = text/plain words = 3168 sentences = 174 flesch = 52 summary = Recent experimental structures of the SARS-CoV-2 S protein receptor binding domain (RBD) in complex with ACE2 provide detailed interface information [4] , [6] ; targeting this interface represents an active area of research for therapeutic development [11] . By first comparing the S protein protomer structure of SARS-CoV-2 to those from previous human coronaviruses, we identified distinct clusters for each virus in the 3-D latent space, where representative structures from these clusters highlight their differences in domain flexibility. To further understand the molecular structures of different human coronavirus S proteins and the oligomeric state of SARS-CoV-2 S protein, we deployed a custom-built deep learning architecture, a convolutional variational autoencoder (CVAE), to encode the high dimensional protein structures from the MD simulations into lower dimensional latent spaces. The size of each resulting matrix was also 191 ⇥ 191, and we merged a total of 10,000 distance matrices of the protomer and trimer of SARS-CoV-2 S protein. cache = ./cache/cord-314321-klb8oe9q.txt txt = ./txt/cord-314321-klb8oe9q.txt === reduce.pl bib === id = cord-316258-7hucqcaj author = Henriques, Elsa S title = Modeling of the Toll-like receptor 3 and a putative Toll-like receptor 3 antagonist encoded by the African swine fever virus date = 2011-01-28 pages = extension = .txt mime = text/plain words = 4079 sentences = 181 flesch = 48 summary = A recently identified novel ASFV viral protein (pI329L) was found to inhibit the Toll-like receptor 3 (TLR3) signaling pathway, TLR3 being a crucial "danger detector." pI329L has been predicted to be a transmembrane protein containing extracellular putative leucine-rich repeats similar to TLR3, suggesting that pI329L might act as a TLR3 decoy. As this later domain shares only remote sequence relationships with the available TLR3 templates, a more complex modeling strategy was employed that combines the iterative implementation of (multi)threading/assembly/refinement (I-TASSER) structural prediction with expertise-guided posterior refinement. On dimerization subsequent to recognition of dsRNA, TLR3 recruits the adaptor protein Toll-interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-b (TRIF) to its cytoplasmic domain, thereby initiating a signaling cascade that results in the secretion of type I interferons and other inflammatory cytokines. cache = ./cache/cord-316258-7hucqcaj.txt txt = ./txt/cord-316258-7hucqcaj.txt === reduce.pl bib === id = cord-322231-jltk42dt author = Huy, Nguyen-Xuan title = Immunogenicity of an S1D epitope from porcine epidemic diarrhea virus and cholera toxin B subunit fusion protein transiently expressed in infiltrated Nicotiana benthamiana leaves date = 2016-08-23 pages = extension = .txt mime = text/plain words = 6951 sentences = 391 flesch = 60 summary = title: Immunogenicity of an S1D epitope from porcine epidemic diarrhea virus and cholera toxin B subunit fusion protein transiently expressed in infiltrated Nicotiana benthamiana leaves After oral administration of transiently expressed CTB–S1D fusion protein, or with bacterial cholera toxin or rice callus expressing mutant cholera toxin 61F, mice exhibited significantly greater serum IgG and sIgA levels against bacterial CTB and S1D antigen, peaking at week 6. For feeding immunization, the mice were fasted 8 h before gavage with 2.0 mL of PBS buffer pH 7.0 containing lyophilized leaf powder, which harbored 100 µg of CTB-S1D fusion protein, or with bacterial cholera toxin-bCT (Sigma) or rice callus-expressed mutant cholera toxin 61 F (Arg to Phe)-rCTX and wild-type (WT) N. Oral immunization with transient expression CTB-S1D fusion protein induced significantly higher anti-CTB, anti-S1D IgG and sIgA levels compared with the control group (Fig. 7 ). cache = ./cache/cord-322231-jltk42dt.txt txt = ./txt/cord-322231-jltk42dt.txt === reduce.pl bib === id = cord-322926-xlwsj3v2 author = Shanmugaraj, Balamurugan title = Plant Molecular Farming: A Viable Platform for Recombinant Biopharmaceutical Production date = 2020-07-04 pages = extension = .txt mime = text/plain words = 4666 sentences = 228 flesch = 31 summary = Given the speed advantages, and proven viability of the plant production platform, the transient expression system in particular could be employed to produce recombinant proteins at high levels to meet the sudden demand for production of viral antigens or antiviral proteins that could be used as research reagents, emergency vaccines (SARS-CoV-2 subunit and virus-like particle vaccines), or other biopharmaceuticals to fight against COVID-19 [25, 124] . Given the speed advantages, and proven viability of the plant production platform, the transient expression system in particular could be employed to produce recombinant proteins at high levels to meet the sudden demand for production of viral antigens or antiviral proteins that could be used as research reagents, emergency vaccines (SARS-CoV-2 subunit and virus-like particle vaccines), or other biopharmaceuticals to fight against COVID-19 [25, 124] . cache = ./cache/cord-322926-xlwsj3v2.txt txt = ./txt/cord-322926-xlwsj3v2.txt === reduce.pl bib === id = cord-320092-0qnvydux author = Ehsani, Sepehr title = COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein date = 2020-10-16 pages = extension = .txt mime = text/plain words = 7536 sentences = 406 flesch = 45 summary = An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. c The position of the disulfide bonds in the sequence of the mature human hepcidin is illustrated along with the potential palmitoylation residues (ten cysteines) of the cytoplasmic tail of the SARS-CoV-2 spike protein. If the sequence similarity reported here is actually playing a significant role at the cellular level, could it be that, although the cellular localizations appear to be different based on current knowledge, the SARS-CoV-2 spike protein cytoplasmic tail can partly mimic the structure of hepcidin and interact with ferroportin? In addition, a notyet-fully-established link of relevance here is the observations of a Kawasaki-disease-like systemic vasculitis syndrome in children infected with the novel Fig. 3 Summary of salient facets of coronavirus spike protein and human hepcidin biology. cache = ./cache/cord-320092-0qnvydux.txt txt = ./txt/cord-320092-0qnvydux.txt === reduce.pl bib === id = cord-319291-6l688krc author = Hung, Chun-Min title = Alignment using genetic programming with causal trees for identification of protein functions date = 2006-09-01 pages = extension = .txt mime = text/plain words = 8941 sentences = 632 flesch = 52 summary = Particularly, the model has three characteristics: (i) it is a hybrid evolutionary model with multiple fitness functions that uses genetic programming to predict protein functions on a distantly related protein family, (ii) it incorporates modified robust point matching to accurately compare all feature points using the moment invariant and thin-plate spline theorems, and (iii) the hierarchical homologies holding up a novel protein sequence in the form of a causal tree can effectively demonstrate the relationship between proteins. The hybrid model, namely Alignment using Genetic programming with Causal Tree (AGCT), is a heuristic evolutionary method that contains three basic components: (i) genetic programming with innerexchanged individual strategy, (ii) causal trees [4, 28, 31] with probabilistic reasoning, and (iii) construction of hierarchical homologies with local block-to-block alignment using the methods of moment invariant and robust points matching (RPM) [24] . cache = ./cache/cord-319291-6l688krc.txt txt = ./txt/cord-319291-6l688krc.txt === reduce.pl bib === id = cord-323768-r7jbm1et author = Lagarda-Diaz, Irlanda title = Legume Lectins: Proteins with Diverse Applications date = 2017-06-12 pages = extension = .txt mime = text/plain words = 6811 sentences = 368 flesch = 41 summary = Because lectins recognize and bind to specific glycoconjugates present on the surface of cells and intracellular structures; they can serve as potential target molecules for developing practical applications in the fields of food; agriculture; health and pharmaceutical research. This review presents the current knowledge of the main structural characteristics of legume lectins and the relationship of structure to the exhibited specificities; provides an overview of their particular antimicrobial; insecticidal and antitumor biological activities and describes possible applications based on the pattern of recognized glyco-targets. The isolation and purification of lectins from seeds of native plants such as Parkinsonia aculeata, Olneya tesota, Acacia constricta, Prosopis juliflora, Cercidium praecox, Caesalpinia caladenia and Phaseolus acutifolius has been described. Purification and characterization of complex carbohydrate specific isolectins from wild legume seeds: Acacia constricta is (vinorama) highly homologous to Phaseolus Vulgaris lectins cache = ./cache/cord-323768-r7jbm1et.txt txt = ./txt/cord-323768-r7jbm1et.txt === reduce.pl bib === id = cord-315570-khm1veuv author = González-Mora, Alejandro title = Bacteriophage-Based Vaccines: A Potent Approach for Antigen Delivery date = 2020-09-04 pages = extension = .txt mime = text/plain words = 9969 sentences = 455 flesch = 40 summary = This system relies on bacteriophages displaying proteins or peptides with high affinity to antigen-presenting cells or the antigen itself and at the same time they carry on their genome an eukaryotic expression cassette encoding a specific antigen with the final aim of increasing the immune response by combining both effects (Figure 1 ) [6] . developed a double-hybrid filamentous bacteriophage fd co-displaying peptides recognized by the Major Histocompatibility Complex (MHC) class I and MHC class II cell surface receptors and epitopes from the antigen MAGE aiming to enhance the anti-tumor immune activity based on CTL responses [62] . Thus, the adjuvant-like effect exhibited by phages in various vaccination studies along with their capacity to effectively present peptides or proteins to the immune system leading to the activation of cellular and humoral immune responses [40] demonstrates that engineered phage particles are a proper strategy to enhance the efficacy and safety of viral particle-based vaccines. cache = ./cache/cord-315570-khm1veuv.txt txt = ./txt/cord-315570-khm1veuv.txt === reduce.pl bib === id = cord-323072-4rsgeag7 author = Han, Xueqing title = The expression of SARS–CoV M gene in P. Pastoris and the diagnostic utility of the expression product date = 2004-12-01 pages = extension = .txt mime = text/plain words = 3741 sentences = 185 flesch = 54 summary = Since the outbreak of SARS in 2003, several laboratory diagnostic methods have been established, including real-time RT-PCR assay, whole-virus-based immunofluorescence assay (IFA), recombinant protein-based enzyme-linked immunosorbent assay (ELISA) and immunochromatographic tests, antigencapturing enzyme-linked immunosorbent assay, and Western blot (WB) assay. To test whether the recombinant M protein is effective as an ELISA antigen for detecting SARS-CoV patient serum, the sera from four healthy people and four SARS patients were used. Detection results of eight human sera by ELISA using purified recombinant M protein as antigen.# 1-4: sera from four healthy people, respectively, # 5-8: sera from four SARS patients, respectively. The results were in complete accordance with those of other assays, thus indicating that the recombinant M protein may be useful as an ELISA antigen for detecting specific antibodies to SARS-CoV in human sera. Recombinant protein-based enzyme-linked imunosorbent assay and immunochromatographic tests for detection of immunoglobulin G antibodies to severe acute respiratory syndrome (SARS) coronavirus in SARS patients cache = ./cache/cord-323072-4rsgeag7.txt txt = ./txt/cord-323072-4rsgeag7.txt === reduce.pl bib === id = cord-320083-0k15w624 author = Leitão, Jorge H. title = Microbial Virulence Factors date = 2020-07-27 pages = extension = .txt mime = text/plain words = 2819 sentences = 140 flesch = 39 summary = Microbial virulence factors encompass a wide range of molecules produced by pathogenic microorganisms, enhancing their ability to evade their host defenses and cause disease [...]. The paper focused on the discovery, properties and substrate specificity of the two proteases, their high specificity towards actin, and discussed their contribution to the invasiveness of Serratia, although further knowledge of the bacterium virulence factors and the cellular response mechanisms is required to fully understand the mechanism of Serratia invasion of the host cell [14] . The roles played by virulence factors produced by bacteria when crossing the central nervous system is also addressed, followed by the review of the specific traits of bacterial species more commonly associated with meningitis [15] . The authors also present a thorough review of the main virulence factors used by the organism, including pyolysin, fimbriae, extracellular matrix-binding proteins, neuraminidases, and ability to form biofilms [17] . From Gene to Protein-How Bacterial Virulence Factors Manipulate Host Gene Expression during Infection cache = ./cache/cord-320083-0k15w624.txt txt = ./txt/cord-320083-0k15w624.txt === reduce.pl bib === id = cord-319754-5isw53wl author = Balgoma, David title = Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update date = 2020-08-31 pages = extension = .txt mime = text/plain words = 12092 sentences = 541 flesch = 41 summary = Some viruses may use different entry mechanisms, this feature being likely dependent upon the membrane lipid composition of the host cell they infect as well as the particular cell surface factor attachment used. The question regarding whether the lipid-raft domains may serve as platforms to concentrate the proteins required for viral entry and, even though some evidence exists, to activate signaling pathways inside the host cell still remains unsolved. More recently, a Ca 2+ -dependent pathway of infection by the Rubella virus (RuV, Rubivirus family, Togaviridae) was demonstrated to proceed through direct binding of the fusion loop in the viral E1 protein to SM/cholesterol-enriched membranes [49] . More recently, a Ca 2+ -dependent pathway of infection by the Rubella virus (RuV, Rubivirus family, Togaviridae) was demonstrated to proceed through direct binding of the fusion loop in the viral E1 protein to SM/cholesterol-enriched membranes [49] . cache = ./cache/cord-319754-5isw53wl.txt txt = ./txt/cord-319754-5isw53wl.txt === reduce.pl bib === id = cord-319722-udqu5jub author = Ng, Eddy W. Y. title = Advances in MALDI Mass Spectrometry in Clinical Diagnostic Applications date = 2013-04-07 pages = extension = .txt mime = text/plain words = 12514 sentences = 594 flesch = 42 summary = One commonly used approach for identification of disease-specific biomarkers is to compare the quantitative biomolecule profiles of plasma/serum specimens from the patients with the target disease and control subjects without the disease. For example, after immunoprecipitation of amyloid-beta peptides from the cerebral spinal fluid, different amyloid-beta isoforms as well as their corresponding stable-isotope labeled internal standards appear as individual peaks of expected m/z values in a MALDI-TOF mass spectrum, and their quantities can be measured with high accuracy with intra-assay CVs <10% [33] . Surface-enhanced laser desorption/ionization TOF mass spectrometry (SELDI-TOF MS) is a variant of MALDI-TOF MS, and is mainly designed for quantitative analysis of proteins in biological samples. It may be because SELDI-TOF MS was the first high-throughput technology that allowed quantitative profiling and comparison of the serum/plasma proteins in a large number of patient samples within a very short period of time. cache = ./cache/cord-319722-udqu5jub.txt txt = ./txt/cord-319722-udqu5jub.txt === reduce.pl bib === id = cord-319658-u0wjgw50 author = Guven-Maiorov, Emine title = Structural host-microbiota interaction networks date = 2017-10-12 pages = extension = .txt mime = text/plain words = 4666 sentences = 294 flesch = 40 summary = To date, challenges in experimental techniques limit large-scale characterization of HMIs. Here we highlight an area in its infancy which we believe will increasingly engage the computational community: predicting interactions across kingdoms, and mapping these on the host cellular networks to figure out how commensal and pathogenic microbiota modulate the host signaling and broadly cross-species consequences. Systems biology approaches that integrate the HMIs with host endogenous protein interaction networks reveal the systematic trends in virulence strategies of pathogens. The availability of genome-wide high throughput omics data makes it possible to associate microbiota with certain host phenotypes at multiple levels and construct host-pathogen interaction networks at the transcriptome [21], proteome Combinatorial effects of microbial effectors and the active host pathways determine the cell response. Mimicry of interactions of critical regulatory nodes in core network modules in the immune system, may be a major way through which pathogens adversely subvert-and commensal microbiota may beneficially modulate-the host cell. cache = ./cache/cord-319658-u0wjgw50.txt txt = ./txt/cord-319658-u0wjgw50.txt === reduce.pl bib === id = cord-324325-rmlrhyf2 author = Chan, Wai S title = Coronaviral hypothetical and structural proteins were found in the intestinal surface enterocytes and pneumocytes of severe acute respiratory syndrome (SARS) date = 2005-05-13 pages = extension = .txt mime = text/plain words = 3733 sentences = 225 flesch = 43 summary = Immunohistochemical studies on different human tissues, including a cohort of nine autopsies, two liver biopsies and intestinal biopsies of SARS patients, further confirmed the existence of coronaviral hypothetical and structural proteins in the cytoplasm of pneumocytes and small intestinal surface enterocytes in SARS patients. In those tissue sections showing positive signals for immunohistochemical staining, we further performed immunohistochemical studies using all other antibodies tested positive in SARS-CoV-infected Vero E6 cells. The cellular distribution of SARS-CoV protein and viral genome in immunohistochemical-positive lung and small intestine sections was further evaluated by immunofluorescence-fluorescence in situ hybridization analysis (Figure 4) . 3 In Vero E6 cells, positive cytoplasmic immunohistochemical signals were detected by Figure 3 Immunohistochemical studies of antipeptide antibody SARS-AbS13a against the nucleocapsid protein on small intestine sections. In addition, in the study of tissue sections, only those cells with viral genome detected by fluorescence in situ hybridization were positive for immunohistochemical stainings for the antipeptide antibodies. cache = ./cache/cord-324325-rmlrhyf2.txt txt = ./txt/cord-324325-rmlrhyf2.txt === reduce.pl bib === id = cord-325043-vqjhiv7p author = Gorbalenya, Alexander E. title = An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication date = 1989 pages = extension = .txt mime = text/plain words = 6805 sentences = 361 flesch = 52 summary = title: An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication These observations, taken together with the results of comparative analysis of the positions occupied by respective proteins (domains) in viral multidomain proteins, suggest that all the NTP-motif-containing proteins of positive-strand RNA viruses are homologous, constituting a highly diverged monophyletic group. Preliminary comparative analysis of the amino acid sequences of the NTP-motif-eontaining proteins of positive-strand RNA viruses by use of the programs DIAGON and OPTAL (see Methods) revealed three distinct families and some additional proteins in whose close relatives the motif was not conserved. In the present study we demonstrate that in a highly diverged group including similar proteins of positive-strand RNA viruses, the consensus sequences of the NTP-motif constitute the most strictly conserved stretches, encompassing four of the five invariant amino acid residues. cache = ./cache/cord-325043-vqjhiv7p.txt txt = ./txt/cord-325043-vqjhiv7p.txt === reduce.pl bib === id = cord-321762-7kiahjyy author = Nandy, Ashesh title = Chapter 5 The GRANCH Techniques for Analysis of DNA, RNA and Protein Sequences date = 2015-12-31 pages = extension = .txt mime = text/plain words = 9780 sentences = 392 flesch = 46 summary = We presented our scheme at the First Indo-US Workshop on Mathematical Chemistry in Shantiniketan, West Bengal, India in 1998 [10] where we reported, as stated in the abstract, that "Geometrisation of macromolecular sequences in the form of a graphical representation provides one … technique where the nucleotides in a gene sequence can be viewed as objects in a 4-dimensional space; the method can be extended, in principle, to include, say proteins, in a 20-dimensional space. This review is a brief introduction to the readers of this new and exciting field of research on graphical representation and numerical characterization (GRANCH) of bio-molecular sequences, based on the talk I presented at the Second Mathematical Chemistry Workshop of the Americas in Bogota, Colombia, in July 2010 [13] . cache = ./cache/cord-321762-7kiahjyy.txt txt = ./txt/cord-321762-7kiahjyy.txt === reduce.pl bib === id = cord-321441-t1v0pu0w author = Yang, Yiming title = Polycistronic Genome Segment Evolution and Gain and Loss of FAST Protein Function during Fusogenic Orthoreovirus Speciation date = 2020-06-29 pages = extension = .txt mime = text/plain words = 8639 sentences = 363 flesch = 41 summary = New phylogenetic analyses that included the atypical waterfowl subgroup of avian reoviruses and recently identified new orthoreovirus species indicate a more complex relationship between reovirus speciation and fusogenic capacity, with numerous predicted internal indels and 5'-terminal extensions driving the evolution of the orthoreovirus' polycistronic genome segments and their encoded FAST and fiber proteins. We further show that two distinct post-speciation genetic events led to the loss of fusion in the waterfowl isolates of avian reovirus, a recombination event that replaced the p10 FAST protein with a heterologous, non-fusogenic protein and point substitutions in a conserved motif that destroyed the p10 assembly into multimeric fusion platforms. MdRVs are divided into two subgroups, the "classical" and "novel" MdRVs. Classical Muscovy duck reoviruses (MdRVc) possess a bicistronic S4 genome segment encoding a truncated fiber protein of 269 residues and a p11 protein that lacks sequence similarity to the p10 FAST proteins of ARV, ARVN, and NBV ( Figure 1B ) [50] . cache = ./cache/cord-321441-t1v0pu0w.txt txt = ./txt/cord-321441-t1v0pu0w.txt === reduce.pl bib === id = cord-319809-33i6lzjd author = Drew, Elliot D. title = Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity date = 2020-07-01 pages = extension = .txt mime = text/plain words = 4573 sentences = 210 flesch = 57 summary = title: Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity RESULTS: Our analyses of this structure have revealed a key potentially druggable pocket where it might be viable to bind pharmaceutical agents to inhibit its ability to infect human cells. The results from the three methods, Autodock vina [12] , Smina [13] and Ledock [14] , were used to generate a list of 4358 poses of commercially-available drugs capable of binding into this Covid-19 spike protein pocket. This study provides a suggested list of pharmaceutical agents, identifying some of them as being from related structure families, that are available on the market and have been sanctioned for use in humans that have been shown to be capable of binding into a druggable pocket in the spike protein of Covid-19. cache = ./cache/cord-319809-33i6lzjd.txt txt = ./txt/cord-319809-33i6lzjd.txt === reduce.pl bib === id = cord-327000-oyg3oyx1 author = Li, Shasha title = Porcine Epidemic Diarrhea Virus and the Host Innate Immune Response date = 2020-05-11 pages = extension = .txt mime = text/plain words = 11098 sentences = 688 flesch = 48 summary = This review highlights the immune evasion mechanisms employed by PEDV, which provides insights for the better understanding of PEDV-host interactions and developing effective vaccines and antivirals against CoVs. Porcine epidemic diarrhea virus (PEDV) is the etiological agent of porcine epidemic diarrhea (PED) that causes an acute and highly contagious enteric disease of swine characterized by vomiting, diarrhea, dehydration, and anorexia in pigs of all ages, especially resulting in severe diarrhea and high mortality rate in piglets. Nsp3 is the largest nsp protein, containing two papain-like protease (PLP1 and PLP2) domains, of which PEDV PLP2 acts as a viral deubiquitinase (DUB), to negatively regulate type I IFN signaling [80] . The evasive strategies utilized by PEDV are classified into four major types: (1) inhibition of RLRs-mediated IFN production pathways, (2) inhibition of the activation of transcription factors responsible for IFN induction, (3) disruption of the signal cascades induced by IFN, and (4) hiding its viral RNA to avoid the exposure of viral RNA to immune sensors. cache = ./cache/cord-327000-oyg3oyx1.txt txt = ./txt/cord-327000-oyg3oyx1.txt === reduce.pl bib === id = cord-323358-05bk91lm author = Bhaskar, Sathyamoorthy title = Engineering protein nanocages as carriers for biomedical applications date = 2017-04-07 pages = extension = .txt mime = text/plain words = 9541 sentences = 557 flesch = 39 summary = We review natural and synthetic protein nanocages that have been modified using chemical and genetic engineering techniques to impart non-natural functions that are responsive to the complex cellular microenvironment of malignant cells while delivering molecular cargos with improved efficiencies and minimal toxicity. 1, 3 Examples of naturederived nanocarriers include protein nanocages such as viruses, ferritin and many others that are formed by the self-assembly of protein subunits, resulting in a cage-like structure. 8 In this review, we focus on natural and synthetic protein scaffolds engineered with specific functional groups to impart non-native functions, including aiding the delivery of active molecules through targeting of malignant cells and overcoming cellular barriers. 3 In addition to cell targeting ability and gene delivery efficiency, these protein-based multifaceted systems have highly ordered spatial configurations, and the stability and functionality of these materials have already been established through intensive research with advances in understanding virus infection, replication and assembly pathways. cache = ./cache/cord-323358-05bk91lm.txt txt = ./txt/cord-323358-05bk91lm.txt === reduce.pl bib === id = cord-321275-7haq0e38 author = Renzi, Fabiana title = Large-scale purification and crystallization of the endoribonuclease XendoU: troubleshooting with His-tagged proteins date = 2006-02-28 pages = extension = .txt mime = text/plain words = 1971 sentences = 101 flesch = 58 summary = The tendency of the recombinant enzyme to aggregate could be reversed upon the addition of chelating agents (EDTA, imidazole): aggregation is a potential drawback when purifying and crystallizing His-tagged proteins, which are widely used, especially in high-throughput structural studies. Subsequent screening resulted in the growth of crystals (300 Â 300 Â 300 mm) in 40% (NH 4 ) 2 SO 4 , 0.2 M sodium citrate pH 6 at 293 K which belonged to space group P3 1 21 but diffracted poorly; the resolution was improved by cocrystallization with 50 mM uridine 5 0 -monophosphate (5 0 -UMP), which may bind to the active site, possibly inducing the stabilization of flexible regions (Fig. 2a) . Large-scale expression of His-tagged XendoU resulted in soluble protein that was heterogeneously aggregated, a condition that affects crystallization (Wilson, 2003) . cache = ./cache/cord-321275-7haq0e38.txt txt = ./txt/cord-321275-7haq0e38.txt === reduce.pl bib === id = cord-326015-ky4y2xjt author = Füllekrug, Joachim title = Protein sorting in the Golgi complex date = 1998-08-14 pages = extension = .txt mime = text/plain words = 3937 sentences = 202 flesch = 50 summary = In this review, we will discuss sorting of resident proteins in the Golgi complex mainly in the context of cisternal maturation [1, 2] . An essential feature of this maturation model is the prediction that Golgi resident proteins are more concentrated in retrograde vesicles than they are in the cisternae of the Golgi apparatus. This shows that Golgi resident enzymes do form gradients across the pathway and that these are unique to the particular protein. The surprising ¢nding that the membrane spanning domain (MSD) of Golgi residents su¤ced to localise reporter molecules to the appropriate part of the pathway suggested that this domain harboured important sorting information (for review, see [22] ). As this form of coatomer is found on Golgi associated transport vesicles [50] , COP I vesicles constitute RTCs. The presence of K(X)KXX or related signals on membrane proteins other than ER residents allows for the possibility that this motif also acts later in the pathway. cache = ./cache/cord-326015-ky4y2xjt.txt txt = ./txt/cord-326015-ky4y2xjt.txt === reduce.pl bib === id = cord-319780-rfj9t99r author = Alexander, S.P.H. title = A rational roadmap for SARS‐CoV‐2/COVID‐19 pharmacotherapeutic research and development. IUPHAR Review 29 date = 2020-05-01 pages = extension = .txt mime = text/plain words = 15196 sentences = 814 flesch = 47 summary = Analysis of the co-crystal structure suggested that the SARS spike protein binds to the active site of angiotensin converting enzyme 2 (ACE2, Li et al., 2005) . A truncated version of human recombinant ACE2, lacking the transmembrane domain, mitigated against SARS-CoV infection of cells (Li et al., 2003) and has been used in animal models to reduce symptoms of severe acute lung failure , diabetic nephropathy (Oudit et al., 2010) and cardiac hypertrophy and fibrosis . A recent cryo-EM structure suggested that ACE2 and B 0 AT1/SLC6A19 form a heterodimer which pairs up through interfaces between the two ACE2 partners (Figure 1) , with the RBD of SARS-CoV-2 spike protein binding to the peptidase active site of ACE2 suggesting that B 0 AT1/SLC6A19 may facilitate entry of the novel coronavirus. Tumor necrosis factor- convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) cache = ./cache/cord-319780-rfj9t99r.txt txt = ./txt/cord-319780-rfj9t99r.txt === reduce.pl bib === id = cord-321013-8pkrg0mx author = McBride, Ruth title = The Coronavirus Nucleocapsid Is a Multifunctional Protein date = 2014-08-07 pages = extension = .txt mime = text/plain words = 10761 sentences = 476 flesch = 44 summary = The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. The M protein is the main core shell component and a 16 amino acid domain (aa 237-252) on the CTD of M protein binds directly to N protein via an ionic interaction, leading to specific genome encapsidation in the budding viral particle [81] [82] [83] .The N protein therefore plays an essential structural role in the CoV virion through a network of interactions with (i) the genomic RNA; (ii) M protein and (iii) other N proteins. Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA cache = ./cache/cord-321013-8pkrg0mx.txt txt = ./txt/cord-321013-8pkrg0mx.txt === reduce.pl bib === id = cord-320790-ley91488 author = Fogg, M. J. title = Application of the use of high‐throughput technologies to the determination of protein structures of bacterial and viral pathogens date = 2006-10-04 pages = extension = .txt mime = text/plain words = 7066 sentences = 320 flesch = 47 summary = Here the impact of several technologies on the structural determination of proteins from human pathogens is illustrated with selected examples, including the parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens. Here the impact of several technologies on the structural determination of proteins from human pathogens is illustrated with selected examples, including the parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens. Further development and uptake of these methodologies (see Aricescu, Assenberg et al., 2006; Aricescu, Lu et al., 2006) is likely to have a major impact on the study of difficult viral targets, as indicated by preliminary results for EBV proteins, where insect-cell expression yielded soluble protein for 50% of the proteins tested (Tarbouriech et al., 2006) Here we illustrate the impact of a number of particular SPINE-based technologies on the structure determination of pathogen targets, namely (i) multiple-construct design for a single target, (ii) optimization of protein solubility, (iii) eukaryotic expression systems, (iv) standardized refolding protocols, (v) surface engineering and (vi) other biophysical characterization. cache = ./cache/cord-320790-ley91488.txt txt = ./txt/cord-320790-ley91488.txt === reduce.pl bib === id = cord-330852-n7j0c4ne author = Fischer, Wolfgang B. title = Mechanism of Function of Viral Channel Proteins and Implications for Drug Development date = 2012-02-23 pages = extension = .txt mime = text/plain words = 23680 sentences = 1178 flesch = 53 summary = By adding data from functional studies like Cys scanning and electrophysiological measurements as mentioned as well as computational modeling data (Sansom and Kerr, 1993; Sansom et al., 1997; Zhong et al., 1998) , an approximate structural model of the tetrameric assembly of the TMDs of M2 with the histidines and tryptophans as important pore lining residues has been generated. Amiloride derivatives block ion channel activity and enhancement of virus-like particle budding caused by HIV-1 protein Vpu Backbone structure of the amantadine-blocked trans-membrane domain M2 protein channel from influenza A virus Molecular dynamics investigation of membrane-bound bundles of the channel-forming transmembrane domain of viral protein U from the Human Immunodeficiency Virus HIV-1 Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes Three-dimensional structure of the channel-forming trans-membrane domain of virus protein "u" (Vpu) from HIV-1 cache = ./cache/cord-330852-n7j0c4ne.txt txt = ./txt/cord-330852-n7j0c4ne.txt === reduce.pl bib === id = cord-332811-kjgah8ts author = Lee, Do Hyun title = Immunoprophylactic effect of chicken egg yolk antibody (IgY) against a recombinant S1 domain of the porcine epidemic diarrhea virus spike protein in piglets date = 2015-06-23 pages = extension = .txt mime = text/plain words = 5898 sentences = 237 flesch = 43 summary = title: Immunoprophylactic effect of chicken egg yolk antibody (IgY) against a recombinant S1 domain of the porcine epidemic diarrhea virus spike protein in piglets A codon-optimized PEDV S1 gene consisting of amino acid residues 25–749 was synthesized and used to establish a stable porcine cell line constitutively expressing a recombinant PEDV S1 protein containing the chicken immunoglobulin Fc fragment at its C-terminus. Moreover, oral passive immunization using chicken IgY raised against the PEDV S1 protein was found to control and prevent PED post-challenge in suckling piglets. All neonatal piglets except for animals in the control group were inoculated orally with 1 ml of the small-intestine homogenate containing 10 4 TCID 50 /ml PEDV field virus determined using real-time RT-PCR as described previously [10] . Immunoprophylactic effect of chicken egg yolk immunoglobulin (IgY) against porcine epidemic diarrhea virus (PEDV) in piglets cache = ./cache/cord-332811-kjgah8ts.txt txt = ./txt/cord-332811-kjgah8ts.txt === reduce.pl bib === id = cord-332344-upsn0zb4 author = Jeswin, Joseph title = Proteomic analysis by iTRAQ in red claw crayfish, Cherax quadricarinatus, hematopoietic tissue cells post white spot syndrome virus infection date = 2016-02-01 pages = extension = .txt mime = text/plain words = 5882 sentences = 285 flesch = 42 summary = To elucidate proteomic changes of Hpt cells from red claw crayfish, Cherax quadricarinatus, we have carried out isobaric tags for relative and absolute quantitation (iTRAQ) of cellular proteins at both early (1 hpi) and late stage (12 hpi) post white spot syndrome virus (WSSV) infection. Generally, these differentially expressed proteins include: 1) the metabolic process related proteins in glycolysis and glucogenesis, DNA replication, nucleotide/amino acid/fatty acid metabolism and protein biosynthesis; 2) the signal transduction related proteins like small GTPases, G-protein-alpha stimulatory subunit, proteins bearing PDZor 14-3-3-domains that help holding together and organize signaling complexes, casein kinase I and proteins of the MAP-kinase signal transduction pathway; 3) the immune defense related proteins such as α-2 macroglobulin, transglutaminase and trans-activation response RNA-binding protein 1. To further identify proteins or pathways altered during viral infection, here we report proteomic responses of crayfish Hpt cells by iTRAQ at both early (1 hpi) and late (12 hpi) stages post WSSV infection accordingly. cache = ./cache/cord-332344-upsn0zb4.txt txt = ./txt/cord-332344-upsn0zb4.txt === reduce.pl bib === id = cord-332317-wrztpeb8 author = Zhang, Xin title = Identification of the interaction between vimentin and nucleocapsid protein of transmissible gastroenteritis virus date = 2015-03-16 pages = extension = .txt mime = text/plain words = 3977 sentences = 241 flesch = 49 summary = Nucleocapsid (N) protein of transmissible gastroenteritis virus (TGEV) packages viral RNA genome to form a ribonucleoprotein complex. The present study thus provides protein-related information about interaction of TGEV N protein with host cell that should be useful for understanding host cell response to coronavirus pathogenesis infection and the underlying mechanism of coronavirus replication. Recently, some reports showed that N protein of TGEV play an important role in host cell for virus replication. Three cellular proteins, hnRNP U, ACTN4, and vimentin, were identified both by GST-N pull down and Co-IP in TGEV-infected cells, which should have more biological importance in the context of infection. The interaction between the cellular vimentin and N protein of TGEV was confirmed in TGEV-infected ST cells. Host cell proteins interacting with the 3 end of TGEV coronavirus genome influence virus replication EF1A interacting with nucleocapsid protein of transmissible gastroenteritis coronavirus and plays a role in virus replication cache = ./cache/cord-332317-wrztpeb8.txt txt = ./txt/cord-332317-wrztpeb8.txt === reduce.pl bib === id = cord-320713-b37c8aye author = Roberts, Lisa O. title = Chapter 9 Viral Strategies to Subvert the Mammalian Translation Machinery date = 2009-10-27 pages = extension = .txt mime = text/plain words = 20205 sentences = 1067 flesch = 48 summary = 6 The rate of translation initiation in mammalian cells is also controlled by sequence elements within the 5 0 -and 3 0 -UTRs of mRNAs which regulate this process by providing sites for interaction of regulatory proteins and RNAs. These include upstream open reading frames (uORFs), microRNA (miRNA) target sites, and polyadenylation elements. 5 It was suggested that alternative eIF4F complexes lacking PABP could selectively promote the synthesis of viral, but not host, proteins, so that KSHV-encoded mRNAs would compete more effectively for host translation machinery in infected cells. Picornavirus translation is directed by internal ribosome entry sites (IRESs) within the 5 0 -UTRs of the viral RNAs. The central one-third of eIF4G, containing the eIF3 and one eIF4A-binding domain, is sufficient to support translation initiation from these IRESs. 43 This allows picornavirus RNAs to compete effectively for the host translation machinery following infection, although the situation appears to be more complicated than this (see Section III). cache = ./cache/cord-320713-b37c8aye.txt txt = ./txt/cord-320713-b37c8aye.txt === reduce.pl bib === id = cord-327199-ggomuomb author = Moerdyk-Schauwecker, Megan title = Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions date = 2014-08-08 pages = extension = .txt mime = text/plain words = 6425 sentences = 288 flesch = 43 summary = In another example, the presence of host complement control proteins such as CD46, CD55 and CD59 in the viral envelope has been shown to protect against antibody dependent complement mediated virus lysis in several viruses including human T cell leukemia/ lymphoma virus type I [16] , human cytomegalovirus [16] , hepatitis C virus [17] , HIV-1 [18, 19] , extracellular enveloped vaccinia virus [20] , simian virus 5 [21] and mumps virus [21] . As discussed in the previous section, proteins not associated with the interior of the virion, including proteins embedded in the host derived viral envelope, can be identified by their absence in ProK treated samples or by a size shift upon ProK treatment. While many of the proteins identified in VSV virions appear to be associated with viral assembly, budding or the host-derived viral envelope, they may also have additional functions that affect virus replication. cache = ./cache/cord-327199-ggomuomb.txt txt = ./txt/cord-327199-ggomuomb.txt === reduce.pl bib === id = cord-330715-olypwdoq author = Sun, Zeyu title = Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications date = 2020-08-30 pages = extension = .txt mime = text/plain words = 5567 sentences = 275 flesch = 50 summary = title: Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications In this study, we report a comprehensive N-glycosylation profile-as well as other PTMs-of the HCoV-19 S protein and hACE2, elucidated by high-resolution mass spectrometry (MS) analyses. To resolve glycan camouflage on the surface of the HCoV-19 S protein and hACE2, intact glycopeptides derived from protease digestion and fractionated by HILIC were directly subjected to LC-MSMS analysis specifically designed to detect peptides with extra molecular weight due to N-glycan attachment. Fig. 2 (c) provides a summary of the most dominant N-glycan composition and predicted structure for each site of the HCoV-19 spike protein and hACE2. When the spike proteins from HCoV-19 and SARS-CoV were compared, it was noticeable that the majority of differences in the glycosylation sites occurred in the distal S1 subunit, resulting in a significant difference in the glycan profile in the outermost canopy of the virus formed by spike trimer clusters. cache = ./cache/cord-330715-olypwdoq.txt txt = ./txt/cord-330715-olypwdoq.txt === reduce.pl bib === id = cord-333262-xvfl7ycj author = Robson, B. title = COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance date = 2020-04-11 pages = extension = .txt mime = text/plain words = 21671 sentences = 953 flesch = 50 summary = The Wuhan and related isolates revealed a coronavirus that resides in the subgenus Sarbecovirus of the genus Betacoronavirus [2] , and although genetically distinct from its predecessor SARS-CoV it appeared to have similar external binding proteins, meaning here the spike glycoprotein discussed extensively in the present paper. In brief summary, the justifications for the ensemble pharmacophore in the coronavirus case, i.e. the contributions to "fuzziness", include parsimony, that proteins and parts of proteins sometimes have more than one function [12] encouraged by limited numbers of accessible sites (due to e.g. glycosylation) and exemplified by parallel alternative mechanisms of cell entry, multiple methods of drug action, escape from scientific defense measures by virus mutation, polymorphism of human proteins involved, different expression levels of human proteins involved, and the potential problem of the "specter of vaccine development" (concerns about missing the appropriate region of the virus that allows common cold viruses to escape the appropriate immune response). cache = ./cache/cord-333262-xvfl7ycj.txt txt = ./txt/cord-333262-xvfl7ycj.txt === reduce.pl bib === id = cord-329625-hx2rsi91 author = You, Jae-Hwan title = A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging date = 2008-08-15 pages = extension = .txt mime = text/plain words = 5645 sentences = 271 flesch = 46 summary = title: A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. To investigate whether the trafficking of N protein between the cytoplasm and the nucleus/nucleolus was associated with microtubules or energy dependent, the mobility of EGFP-PRRSV-N protein was compared in 3D4/31 cells incubated at 37°C in the presence and absence of nocodazole (60ng/ml nocodazole (Sigma) for 16h), a microtubule inhibitor, or incubated at 10°C. In approximately 10% of cells expressing EGFP-PRRSV-N protein fluorescence was observed in the cytoplasm, but only if imaging was adjusted so that the fluorescent signal in the nucleus/nucleolus was above the linear range (for example Fig. 8C, lower panels) . cache = ./cache/cord-329625-hx2rsi91.txt txt = ./txt/cord-329625-hx2rsi91.txt === reduce.pl bib === id = cord-325282-20l9xcmg author = Helal, Mohamed A. title = Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia date = 2020-09-16 pages = extension = .txt mime = text/plain words = 6739 sentences = 365 flesch = 53 summary = title: Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The entry of the virus into host cells is facilitated by binding of its transmembrane spike (S) protein with angiotensin-converting enzyme 2 (ACE-2) receptor (Hoffmann et al., 2020) . To understand the mechanism of interaction of the SARS-CoV-2 spike protein with the CD147 receptor, we have performed a four-stage in-silico study. The recently reported crystal structure of SARS-Cov-2 spike protein complex with ACE2 (PDB ID: 6LZG) reveals that the virus utilizes the external subdomain of the spike Receptor Binding Domain (RBD) to recognize the human ACE2 receptor . cache = ./cache/cord-325282-20l9xcmg.txt txt = ./txt/cord-325282-20l9xcmg.txt === reduce.pl bib === id = cord-332948-h297ukuu author = Olotu, Fisayo A. title = Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. date = 2020-10-16 pages = extension = .txt mime = text/plain words = 5176 sentences = 315 flesch = 51 summary = authors: Olotu, Fisayo A.; Omolabi, Kehinde F.; Soliman, Mahmoud E.S. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. 30 Identification of other functional (allosteric) sites on the prefusion S protein could present another dynamic and effective approach of preventing SARS-CoV-2 infectivity relative to its interaction with the host cell ACE2 and proteases. 53 Relatively, this study was implemented to (i) identify potential druggable sites across the S1 and S2 domains of the SARS-CoV-2 S protein other than the RBD-hACE2 interface (ii) perform high-throughput (virtual) screening of ~1500 FDA approved drugs against the most druggable site(s) (iii) investigate the binding dynamics and interaction mechanisms of the compounds and their consequential effects on the S-protein RBD-ACE2 complex. We believe this systematic study will be able to provide structural and molecular insights into possible allosteric sites on SARS-CoV-2 S protein suitable for selective targeting and structureComputational methodologies cache = ./cache/cord-332948-h297ukuu.txt txt = ./txt/cord-332948-h297ukuu.txt === reduce.pl bib === id = cord-330337-d41imvo7 author = Basu, Souradip title = Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins date = 2020-10-20 pages = extension = .txt mime = text/plain words = 6428 sentences = 311 flesch = 52 summary = Our observations and analysis direct us to identify that all the major mutations have a negative impact in context of stability of the viral proteins under study and the mutant proteins suffer both structural and functional alterations as a result of the mutations. The secondary structure of the wild type and the mutant proteins along with their degree of disordered residues and accessible surface area was predicted using the primary sequence of the protein. Each of the seven proteins were assigned a score of either '-1' or '0', for each of the four computational tools used for epitope prediction, where '-1' corresponds to any change in number or binding efficacy of antigenic determinants, that may have surfaced because of mutation and '0' corresponds to no changes between wild type and mutant forms. I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure cache = ./cache/cord-330337-d41imvo7.txt txt = ./txt/cord-330337-d41imvo7.txt === reduce.pl bib === id = cord-329844-w969lczb author = Robson, B. title = Bioinformatics studies on a function of the SARS-CoV-2 spike glycoprotein as the binding of host sialic acid glycans date = 2020-06-08 pages = extension = .txt mime = text/plain words = 15903 sentences = 664 flesch = 49 summary = The location of any sialic acid glycan binding region of SARS-CoV-2 is, a priori unclear, although intuitively (a) it would likely be associated with the cap or knob at the outer end of the spike protein, or (b) at least not involve exactly the same domain as is required for other important functions. An algorithm for predicting the domains and proteins involved in sialic acid glycan binding is developed in the course of the project described in Results Section 4, but this is primarily of a highly empirical nature. This, plus a sequence rather than three dimensional structure perspective, and a specific focus on binding sialic acid glycans rather than sugars in general, resulted in a substantial difference in scores from another major method of predicting sugar binding regions of proteins also discussed later below. cache = ./cache/cord-329844-w969lczb.txt txt = ./txt/cord-329844-w969lczb.txt === reduce.pl bib === id = cord-328003-yovp8squ author = Duan, Liangwei title = The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date = 2020-10-07 pages = extension = .txt mime = text/plain words = 7346 sentences = 386 flesch = 46 summary = Here, we provide a comprehensive overview of the wealth of research related to the SARS-CoV-2 S glycoprotein biosynthesis, structure, function, and antigenicity, aiming to provide useful insights into the design and development of the S protein-based vaccines as well as therapeutics to prevent or treat the ongoing global spread of SARS-CoV-2/COVID-19. Prefusion structures of human coronavirus HKU1 (HCoV-HKU1) and mouse hepatitis virus S protein ectodomains without two consecutive proline mutations reveal only fully closed conformation (37, 42) , similar to that observed for a full-length, wild-type prefusion form of the SARS-CoV-2 S glycoprotein (41) . Therefore, SARS-CoV-2 evades immune surveillance also through conformational masking, which is well-documented for HIV-1 (43, 44) ; while at the same time, the S protein could transiently sample the functional state to engage ACE2, consistent with the notion that the fusion glycoprotein of highly pathogenic viruses have evolved to perform its functions while evading host neutralizing antibody responses. cache = ./cache/cord-328003-yovp8squ.txt txt = ./txt/cord-328003-yovp8squ.txt === reduce.pl bib === id = cord-329840-f3dsu36p author = Hati, Sanchita title = Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor date = 2020-05-11 pages = extension = .txt mime = text/plain words = 2497 sentences = 173 flesch = 51 summary = In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. In the backdrop of significant mortality rate for SARS-CoV-2 (hereinafter referred to as CoV-2) infection, it is important to know if the thiol-disulfide balance plays any role on the binding of the spike glycoprotein on to the host cell receptor protein ACE2. Using these reported structures, molecular dynamics simulations and electrostatic field calculations were performed to explore the impact of thioldisulfide balance on CoV/CoV-2 and ACE2 binding affinities. The structural and dynamical changes due to the change in the redox states of cysteines in the interacting proteins were analyzed and their effects on binding free energies were studied. cache = ./cache/cord-329840-f3dsu36p.txt txt = ./txt/cord-329840-f3dsu36p.txt === reduce.pl bib === id = cord-325825-0lyt8gfq author = Griffiths, Samantha J. title = A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date = 2013-08-08 pages = extension = .txt mime = text/plain words = 12504 sentences = 601 flesch = 45 summary = Host factors (HFs) which positively or negatively regulate HSV-1 replication were identified by screening a druggable genome siRNA library (4 siRNAs per gene) targeting 7,237 human genes against a HSV-1 reporter virus expressing the enhanced green fluorescent protein (eGFP; HSV-1 strain C12) in the epithelial Hela cell line, due to their ease of transfection and susceptibility to HSV-1 infection [34] . Combined bioinformatic analyses of protein interaction and siRNA depletion screens found a significant functional enrichment for proteins involved in transcription, and identified multi-protein complexes enriched for pro-viral HFs which strongly inhibited HSV-1 upon depletion, including the RNA-polymerase II, eIF3 and Mediator complexes ( Figure 3a) . Furthermore, qPCR analysis found depletion of Med23 inhibited the induction of IFN-l expression following HSV-1 infection of A549 cells in comparison to cells transfected with the RSCF siRNA control ( Figure 4e ). cache = ./cache/cord-325825-0lyt8gfq.txt txt = ./txt/cord-325825-0lyt8gfq.txt === reduce.pl bib === id = cord-324640-2zhaknbi author = Munday, Diane C. title = Quantitative Proteomic Analysis of A549 Cells Infected with Human Respiratory Syncytial Virus date = 2010-07-20 pages = extension = .txt mime = text/plain words = 12318 sentences = 588 flesch = 39 summary = Although RNA synthesis and virus assembly occur in the cytoplasm, HRSV is known to induce nuclear responses in the host cell as replication alters global gene expression. More recently, 2DE was used to compare the potential effect of several different negative strand RNA viruses, including HRSV, parainfluenza virus, human metap-neumovirus, measles virus, and influenza virus, on the host cell proteome with common changes in proteins involved with apoptosis and endoplasmic reticulum stress being highlighted (27) . Together, the indirect immunofluorescence confocal microscopy images supported the observations from the quantitative proteomic analysis that the abundance of mitochondrial proteins (particularly pore proteins) was altered in HRSV-infected cells. Potential Disruption of Proteins Involved in Nucleocytoplasmic Trafficking-Network pathway analysis indicated that the abundance of nuclear pore complex components and proteins involved in the nucleocytoplasmic trafficking of proteins and RNA differed between HRSV-infected and mock-infected cells (Fig. 4) . cache = ./cache/cord-324640-2zhaknbi.txt txt = ./txt/cord-324640-2zhaknbi.txt === reduce.pl bib === id = cord-333309-21czobqy author = Byun, Hyewon title = ERAD and how viruses exploit it date = 2014-07-03 pages = extension = .txt mime = text/plain words = 11735 sentences = 630 flesch = 45 summary = Interaction of lectin-type and other chaperones with ERAD substrates allows association with members of the protein disulfide isomerase (PDI) family, which generally are characterized by one or more thioredoxin-like motifs (CXXC; Brodsky and Skach, 2011) . In contrast to the rhomboid proteases, the Derlins lack proteolytic activity, suggesting that these proteins bind to ERAD substrates and target them to E3 ligases for ubiquitination and to p97 for membrane extraction (Brodsky, 2012) . These ubiquitin ligases are members of the cytosolic SCF (S-phase kinase-associated protein 1 (Skp1)-Cullin 1 (Cul1)-F-box) family, where the F-box components of the SCF complex recognize the N-glycans of the retrotranslocated substrate, e.g., Fbs1 and Fbs2 (Yoshida, 2007) . A proteasomal ATPase contributes to dislocation of endoplasmic reticulum-associated degradation (ERAD) substrates The viral E3 ubiquitin ligase mK3 uses the Derlin/p97 endoplasmic reticulum-associated degradation pathway to mediate down-regulation of major histocompatibility complex class I proteins cache = ./cache/cord-333309-21czobqy.txt txt = ./txt/cord-333309-21czobqy.txt === reduce.pl bib === id = cord-323331-80d01l6f author = Li, Jie title = Golgi Structure and Function in Health, Stress, and Diseases date = 2019-01-01 pages = extension = .txt mime = text/plain words = 13448 sentences = 930 flesch = 50 summary = Mechanistically, GRASP proteins form homodimers via the N-terminal PDZ domains, and dimers from adjacent Golgi cisternae further oligomerize in trans and function as the "glue" that tethers the cisternae into a stack (Wang et al. Other than the well-studied GRASP65-GM130 and GM130-p115-giantin complexes, the GRIP domain containing golgins are another group of proteins associated with the Golgi structure. Depletion of αSNAP in p53 null or Bax null cells still results in apoptosis, indicating that the anti-apoptotic function is independent of p53 and Bax. Interestingly, αSNAP depletion induces apoptosis independent of the cleavage of Golgi proteins such as GRASP65, golgin-160, and p115 but rather by dysregulation of ER-Golgi vesicle cycling and possibly through ER stress (Naydenov et al. The coiled-coil membrane protein golgin-84 is a novel rab effector required for Golgi ribbon formation Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis cache = ./cache/cord-323331-80d01l6f.txt txt = ./txt/cord-323331-80d01l6f.txt === reduce.pl bib === id = cord-337032-s4g4g80w author = Gupta, Manoj Kumar title = In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel date = 2020-04-15 pages = extension = .txt mime = text/plain words = 3964 sentences = 191 flesch = 52 summary = Considering this, in the present study, authors employed computational approaches for studying the structure as well as function of the human 'SARS-CoV2 E' protein as well as its interaction with various phytochemicals. Result obtained revealed that α-helix and loops present in this protein experience random movement under optimal condition, which in turn modulate ion channel activity; thereby aiding the pathogenesis caused via SARS-CoV2 in human and other vertebrates. By considering the above information, in the present study, authors employed computational approach for identifying the best possible structure of the 'SARS-CoV2 E' protein present in the PDB database to understand its structure and function as well as its behaviour towards various phytochemicals. Subsequently, molecular docking of the 'SARS-CoV2 E' protein with ligands having 250 conformations using the AutoDock tool revealed that the best ten phytochemicals with minimal binding energy are TIP006452 (Belachinal), TIP005365 (Macaflavanone E), TIP003272 (Vibsanol B), TIP003258 (14 R Ã ,15-Epoxyvibsanin C), TIP005363 (Macaflavanone C), TIP000749 (Luzonoid D), TIP008605 (Grossamide K), TIP009461 ((-)-Blestriarene C), TIP005366 (Macaflavanone F) and TIP005783 (Dolichosterone). cache = ./cache/cord-337032-s4g4g80w.txt txt = ./txt/cord-337032-s4g4g80w.txt === reduce.pl bib === id = cord-325943-3hvy7b7c author = Bouwman, Kim M. title = Guinea Fowl Coronavirus Diversity Has Phenotypic Consequences for Glycan and Tissue Binding date = 2019-05-01 pages = extension = .txt mime = text/plain words = 4810 sentences = 265 flesch = 51 summary = Glycan array analysis revealed that, in addition to the previously elucidated biantennary di-N-acetyllactosamine (diLacNAc) receptor, viral attachment S1 proteins from GfCoV/2014 and GfCoV/2011 can bind to glycans capped with alpha-2,6-linked sialic acids. Our data indicate that diversity in GfCoV viral attachment proteins results in differences in degrees of affinity for glycan receptors, as well as altered avidity for intestinal tract tissues, which might have consequences for GfCoV tissue tropism and pathogenesis in guinea fowls. Glycan and tissue binding analyses of GfCoV/2011 and GfCoV/2014 recombinant spike S1 proteins revealed that while both proteins had the same specificities, GfCoV/2014 S1 had a much higher affinity toward glycan receptors and tissues of the lower gastrointestinal tract, in agreement with the observed replication of the virus in these tissues from field cases. cache = ./cache/cord-325943-3hvy7b7c.txt txt = ./txt/cord-325943-3hvy7b7c.txt === reduce.pl bib === id = cord-327934-hjimlb6i author = Acar, Delphine D. title = Identification of peptide domains involved in the subcellular localization of the feline coronavirus 3b protein date = 2019-10-01 pages = extension = .txt mime = text/plain words = 6784 sentences = 352 flesch = 44 summary = Transfection of different cell types with FCoV 3b fused to enhanced green fluorescent protein (EGFP) or 3×FLAG confirmed localization of FCoV 3b in the mitochondria and nucleoli. Transport of larger proteins to the nucleus, however, is an ATP-dependent active process driven by nuclear localization signals (NLSs), which are typically characterized by clusters of basic amino acids (reviewed in [38] [39] [40] [41] [42] ). The nucleocapsid proteins of several members of the order Nidovirales, such as porcine reproductive and respiratory syndrome virus (PRRSV, family Arteriviridae) [70, [77] [78] [79] [80] , transmissible gastroenteritis virus (TGEV) [81] , mouse hepatitis virus (MHV) [81, 82] and infectious bronchitis virus (IBV) [82] [83] [84] [85] (family Coronaviridae), also target the nucleolus and have been shown to incorporate one or more potential NLSs. Similarly, the SARS-CoV 3b protein was predicted to have two overlapping NLSs, a pat4 and bipartite motif, that were shown to be associated with nuclear (nucleolar) localization [27] . cache = ./cache/cord-327934-hjimlb6i.txt txt = ./txt/cord-327934-hjimlb6i.txt === reduce.pl bib === id = cord-324667-wmhdw1qs author = Nishtala, Krishnatej title = Tear biomarkers for keratoconus date = 2016-08-04 pages = extension = .txt mime = text/plain words = 4082 sentences = 226 flesch = 36 summary = Advances in technologies such as mass spectrometry and NMR have helped in studying and understanding molecular changes in the tear proteome, lipidome and metabolome relating to an ocular disease condition. Enzyme linked immunosorbent assay (ELISA) analysis of capillary collected tears in 28 [61] , 30 [62] and 94 [63] patients with keratoconus in three different studies showed elevated levels of inflammatory markers IL-6, TNFα and MMP9. Protein levels of gross cystic disease fluid protein-15/ prolactin-inducible protein (PIP) and zinc-alpha-2glycoprotein have been found to be elevated in tears of 36 patients by proteomic analysis, suggesting their application as prognostic markers for keratoconus [72] ( Table 2 ). A multi-omics approach integrating data from proteomics, lipidomics and metabolomics is the need of the hour for studying tear fluid as an important source of biomarkers in keratoconus to lead to effective prognosis and treatment of the disease. cache = ./cache/cord-324667-wmhdw1qs.txt txt = ./txt/cord-324667-wmhdw1qs.txt === reduce.pl bib === id = cord-330475-mameyzih author = Shi, Da title = Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus date = 2014-03-13 pages = extension = .txt mime = text/plain words = 5570 sentences = 296 flesch = 44 summary = Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. The B23.1-DsRed fusion protein was used to tag the nucleolus, so we could analyze nucleolar localization properties and colocalization in cotransfected cells by live cell imaging (direct fluorescence) or confocal microscopy. These expression plasmids were transfected into Vero E6 cells, the nuclear was stained with DAPI at 24 h post-transfection indicated that amino acids 148-220 directed AcGFP to the cytoplasm and nucleus and had a subcellular localization similar to AcGFP. cache = ./cache/cord-330475-mameyzih.txt txt = ./txt/cord-330475-mameyzih.txt === reduce.pl bib === id = cord-341324-f9g9gitn author = Rojas, José M. title = Viral pathogen-induced mechanisms to antagonize mammalian interferon (IFN) signaling pathway date = 2020-10-21 pages = extension = .txt mime = text/plain words = 10837 sentences = 595 flesch = 42 summary = This includes for instance cooperating in PRR recognition of viral PAMPs, stabilizing signaling complexes to improve their resistance to degradation, stopping virus entry, blocking viral capsid formation, impairing trafficking and budding of virions from the infected cells, but also modulating the IFN response to avoid the toxicity of these potent immune mediators. The phosphorylated STAT1/STAT2 heterodimer associates with interferon regulatory factor 9 (IRF9) to form the transcriptional factor complex ISGF3, which translocate to the nucleus and binds the IFN-response elements (ISRE) in ISG promoters leading to the expression of ISG products [36] (Fig. 2 The oligoadenylate synthetase (OAS)-latent RNase (RNase L) pathway is another IFN-inducible pathway that provides the cell with an effector mechanism upon recognition of viral dsRNA (reviewed in [44] ). cache = ./cache/cord-341324-f9g9gitn.txt txt = ./txt/cord-341324-f9g9gitn.txt === reduce.pl bib === id = cord-325559-di8lljoi author = Cappello, Francesco title = Does SARS-CoV-2 Trigger Stress-Induced Autoimmunity by Molecular Mimicry? A Hypothesis date = 2020-06-29 pages = extension = .txt mime = text/plain words = 5204 sentences = 298 flesch = 44 summary = Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced disease (COVID-19) is a planetary emergency that is urging many research groups to redirect their efforts and to channel their experience towards understanding its pathogenesis. These human epitopes, in turn, can be recognized by circulating antibodies made against crossreactive microbial antigens; these antibodies behave like autoantibodies, causing the destruction of the stressed cells, representing a typical example of pathology caused by molecular mimicry and manifested as autoimmunity [30] . We hypothesize that, at the basis of the generalized activation of the immune system, there are molecular mimicry phenomena: the antibodies produced against the virus could turn into autoantibodies against crossreactive proteins expressed on human cells, causing autoimmunity with cell destruction. We hypothesize that, at the basis of the generalized activation of the immune system, there are molecular mimicry phenomena: the antibodies produced against the virus could turn into autoantibodies against crossreactive proteins expressed on human cells, causing autoimmunity with cell destruction. cache = ./cache/cord-325559-di8lljoi.txt txt = ./txt/cord-325559-di8lljoi.txt === reduce.pl bib === id = cord-329493-ueqlhgn0 author = Stadler, Konrad title = SARS — beginning to understand a new virus date = 2003 pages = extension = .txt mime = text/plain words = 5146 sentences = 248 flesch = 51 summary = A new infectious disease, known as severe acute respiratory syndrome (SARS), appeared in the Guangdong province of southern China in 2002. When Thiel and colleagues 20 isolated one genomic and eight subgenomic RNAs from the FRA strain and sequenced their 5′ ends, they identified a conserved sequence (5′ACGAAC3′) that was located in coronaviruses: S, spike protein; E, envelope protein; M, membrane glycoprotein; and N, nucleocapsid protein. Alternatively, these antigens could be delivered by DNA immunization by Figure 6 | The S1 domain of SARS-CoV spike is structurally related to group 2 coronaviruses. Schematic representation of cysteine positions in the S1 domains of group 1, 2 and 3 coronaviruses, compared with the SARS-CoV spike protein. The complete genome sequence of a SARS-CoV isolate (FRA) and experimental data on its key RNA elements and protein functions are described. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection cache = ./cache/cord-329493-ueqlhgn0.txt txt = ./txt/cord-329493-ueqlhgn0.txt === reduce.pl bib === id = cord-328046-5us4se5o author = Xu, H. Y. title = Further Identification and Characterization of Novel Intermediate and Mature Cleavage Products Released from the ORF 1b Region of the Avian Coronavirus Infectious Bronchitis Virus 1a/1b Polyprotein date = 2001-09-30 pages = extension = .txt mime = text/plain words = 5643 sentences = 279 flesch = 51 summary = In cells infected with avian coronavirus infectious bronchitis virus (IBV), three proteins of 100, 39, and 35 kDa, respectively, were previously identified as mature cleavage products released from the 1b region of the 1a/1b polyprotein by the 3C-like proteinase. Immunofluorescent staining of IBV-infected cells and cells expressing individual cleavage products showed that the 100-, 68-, and 58-kDa proteins were associated with the membranes of the endoplasmic reticulum, and the 39and 35-kDa proteins displayed diffuse distribution patterns. Taken together with the Q 3928 -S 2929 dipeptide bond (encoded by nucleotides 12310-12315) identified as the N-terminal cleavage site of the 100-kDa protein, cleavage at these positions would result in the release of five mature products with molecular masses of approximately 100, 68, 58, 39, and 35 kDa. Among them, the 100-, 39-, and 35-kDa proteins were specifically identified in IBV-infected cells (Liu et al., 1994 . cache = ./cache/cord-328046-5us4se5o.txt txt = ./txt/cord-328046-5us4se5o.txt === reduce.pl bib === id = cord-325230-3kg4oe4g author = Agol, Vadim I. title = Viral security proteins: counteracting host defences date = 2010-11-09 pages = extension = .txt mime = text/plain words = 8716 sentences = 426 flesch = 41 summary = These proteins include: capsid proteins; an RNA-dependent RNA polymerase (3D pol ); a protein (VPg, or 3B) that serves as a primer for the initiation of RNA synthesis; an ATPase with a conserved superfamily 3 helicase motif (2C ATPase ) and an essential but poorly defined role in viral RNA replication; a chymotrypsin-like protease (3C pro ), which, as the mature protein or as a precursor, is a major factor in polyprotein processing; two hydrophobic membrane-binding proteins (2B and 3A) that participate in the generation of a virus-friendly environment; and, flanking the precursor of the capsid proteins, one or two highly variable proteins (L and 2A), the structure and functions of which are the subject of this Review. cache = ./cache/cord-325230-3kg4oe4g.txt txt = ./txt/cord-325230-3kg4oe4g.txt === reduce.pl bib === id = cord-327883-s9nbr5y8 author = nan title = Section Virology date = 1990-03-31 pages = extension = .txt mime = text/plain words = 10576 sentences = 571 flesch = 48 summary = By improving the enzyme-linked immunosorbent assay (ELISA) for HSV-2-antibodies and additional testing of sera by Western blot, we were able to specifically identify HSV-l-and HSV-2-antibodies in serum samples. To get some insight into the molecular basis of processes controlling the viral expression we studied the sequence-specific DNA-protein interactions within the genomic regulatory regions. for Med. Microbiology, Univ., D-5300 Bonn Semiquantitative detection of Hepatitis B Virus (HBV) DNA in sera of infected individuals has become an important means of modern serological hepatitis diagnostics. THOMSSEN 1 In the course of acute Epstein-Barr virus (EBV) infection IgM antibodies always occur against two cellular antigens that were characterized as proteins with a molecular weight of 26 kD (p26) and 29 kD (p29), respectively. The frequency and specificity of antibodies to P-gene encoded proteins of human hepatitis B virus was tested in sera of acute and chronically infected patients with and without hepatocellular carcinoma (HCC). cache = ./cache/cord-327883-s9nbr5y8.txt txt = ./txt/cord-327883-s9nbr5y8.txt === reduce.pl bib === id = cord-338485-4zqeq1se author = Aiking, Harry title = The next protein transition() date = 2018-07-27 pages = extension = .txt mime = text/plain words = 6836 sentences = 344 flesch = 49 summary = With respect to sustainability, this is none too early, for there is a growing consensus that animal protein has disproportionate environmental impacts, particularly when produced in intensive production systems employing massive use of feed crops (Aiking, 2014; McMichael, Powles, Butler, & Uauy, 2007; Smil, 2001; Steinfeld et al., 2006; Westhoek et al., 2011) . Animal protein products such as meat and dairy are important to them from an economic perspective, but when employing intensive production systems these are wasteful of plant protein from an environmental point of view and inherently, therefore, wasteful of the resources required to grow feed crops, such as land, water, phosphate and fuel. Increase awareness of the impacts of animal-based protein on the environment, the urgency of this issue and the availability of solutions, but take into account that science-based health and sustainability arguments in favour of a diet change do not sufficiently reach consumers or are too difficult for them to comprehend (de Boer & Aiking, 2017) . cache = ./cache/cord-338485-4zqeq1se.txt txt = ./txt/cord-338485-4zqeq1se.txt === reduce.pl bib === id = cord-327744-5k8np850 author = Munteanu, Cristian Robert title = Multi-target QPDR classification model for human breast and colon cancer-related proteins using star graph topological indices date = 2009-03-21 pages = extension = .txt mime = text/plain words = 4738 sentences = 277 flesch = 57 summary = In conclusion, we shown that, using simple input data such is the primary protein sequence and the simples linear analysis, it is possible to obtain accurate classification models that can predict if a new protein related with two types of cancer. The primary protein sequence is transformed in connectivity star graph's TIs that are used by a statistical linear method in order to construct an input-coded multi-target classification model. The best classification model predicted the probability of presence in HBC/HCC cancer for any of these mutated proteins and the results were analysed with two-way joining clustering analysis method (tw-JCA) from STATISTICA (StatSoft.Inc., 2002). This study is proposing two cancer/non-cancer input-coded multi-target classification models for HBC and HCC using the star network TIs of the protein amino acid sequences. cache = ./cache/cord-327744-5k8np850.txt txt = ./txt/cord-327744-5k8np850.txt === reduce.pl bib === id = cord-329149-1giy1fow author = Martinez-Martin, Nadia title = Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions date = 2017-02-22 pages = extension = .txt mime = text/plain words = 11180 sentences = 487 flesch = 27 summary = Despite SPR and related methods offering higher sensitivity for detection of transient Biochemical and MS PDGFR identified as a high affinity cell surface receptor for the CMV gHgLgO protein complex [21] Herpes simplex viruses (HSVs) Biophysical Secreted and plasma membrane-expressed glycoprotein G targets a specific set of human chemokines with high affinity [22] Human immunodeficiency virus type 1 (HIV) Despite the undoubted importance of the biochemical and biophysical approaches to the study of host-pathogen interactions, the aforementioned limitations have motivated the development of alternative technologies for large-scale analysis of ePPIs. From the initial utilization of microarrays for detection of PPI over a decade ago, human proteome chips containing thousands of recombinant proteins have been generated, some of which are now commercially available. cache = ./cache/cord-329149-1giy1fow.txt txt = ./txt/cord-329149-1giy1fow.txt === reduce.pl bib === id = cord-337825-ujq9mxk7 author = Chen, Bin title = Overview of lethal human coronaviruses date = 2020-06-10 pages = extension = .txt mime = text/plain words = 13423 sentences = 761 flesch = 51 summary = Coronaviruses are the largest +ssRNA viruses and contain at least 14 ORFs, 16 protein combines with viral RNA to form a nucleocapsid, which is involved in the replication of SARS-CoV and is the most abundant protein in virus-infected cells. MERS-CoV can infect T-cells from human lymphoid organs and causes the peripheral blood inducing apoptosis by intrinsic and extrinsic pathways, thus avoiding host immune response detection method, Nanopore Targeted Sequencing, also has the potential for efficiently detecting viruses in a reasonable time. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine cache = ./cache/cord-337825-ujq9mxk7.txt txt = ./txt/cord-337825-ujq9mxk7.txt === reduce.pl bib === id = cord-328483-sj8i9ss2 author = Jaegle, Mike title = Protein‐Templated Fragment Ligations—From Molecular Recognition to Drug Discovery date = 2017-05-31 pages = extension = .txt mime = text/plain words = 9580 sentences = 543 flesch = 44 summary = Protein-templated fragment ligations are chemical reactions between small molecules ("fragments") utilizing aproteinss urface as areaction vessel to catalyzethe formation of aprotein ligand with increased binding affinity.T he approache xploits the molecular recognition of reactive small-molecule fragments by proteins both for ligand assembly and for the identification of bioactive fragment combinations.Inthis way, chemical synthesis and bioassayare integrated in one single step.T his Review discusses the biophysical basis of reversible and irreversible fragment ligations and gives an overview of the available methods to detect protein-templated ligation products.T he chemical scope and recent applications as well as future potential of the concept in drug discovery are reviewed. cache = ./cache/cord-328483-sj8i9ss2.txt txt = ./txt/cord-328483-sj8i9ss2.txt === reduce.pl bib === id = cord-022940-atbjwpo5 author = nan title = Poster Sessions date = 2016-09-07 pages = extension = .txt mime = text/plain words = 241182 sentences = 12746 flesch = 47 summary = We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment. cache = ./cache/cord-022940-atbjwpo5.txt txt = ./txt/cord-022940-atbjwpo5.txt === reduce.pl bib === id = cord-330668-7aw17jf8 author = Chen, Cheng-Chang title = ORF8a of SARS-CoV forms an ion channel: Experiments and molecular dynamics simulations date = 2011-02-28 pages = extension = .txt mime = text/plain words = 4806 sentences = 274 flesch = 56 summary = The protein is synthesized using solid phase peptide synthesis and reconstituted into artificial lipid bilayers that forms cation-selective ion channels with a main conductance level of 8.9±0.8pS at elevated temperature (38.5°C). Computational modeling studies including multi nanosecond molecular dynamics simulations in a hydrated POPC lipid bilayer are done with a 22 amino acid transmembrane helix to predict a putative homooligomeric helical bundle model. Before embedding low energy models into lipid bilayers two amino acids residues of the protein were added at the N and C termini of each of the helices in each bundle model to account for the consequences of their interaction with the lipid bilayer during the simulation. The idealized monomeric TM helix based on the consensus sequence Leu-3 to Val-20 (Fig. 1A) shows clustering of hydrophilic residues (Thr-8, Ser-11, Ser-14 and Thr-18) on one side suggesting that the four hydrophilic amino acids form the lumen of the pore in a homooligomeric helical bundle channel model. cache = ./cache/cord-330668-7aw17jf8.txt txt = ./txt/cord-330668-7aw17jf8.txt === reduce.pl bib === id = cord-329448-kxxy60x9 author = Kumari, Sudha title = Endocytosis unplugged: multiple ways to enter the cell date = 2010-02-02 pages = extension = .txt mime = text/plain words = 11521 sentences = 541 flesch = 31 summary = These factors include one or more underlying principle in cargo enrichment, necessitating specific coat and coat-associated protein assembly, a scission mechanism, and a means to integrate these steps; several molecules and membrane parameters can influence and diversify an endocytic process. CtBP1/BARS (C-terminal-binding protein-1/brefeldin A ribosylation substrate) proteins were originally demonstrated to regulate dynamin-independent fluid uptake in a variety of cell lines, and were later reported to localize to the site of and affect macropinosome membrane closure in a phosphorylation-dependent manner [36] . Overexpression of dominant negative, GTP-binding mutants of dynamin also blocked receptor-mediated endocytosis in various cells, suggesting a role for the GTPase activity of dynamin in the clathrin-dependent endocytic process outside the nervous system. The identification of an endocytic pathway as distinct has been primarily based on associated cargo proteins or lipids, and molecular regulators; the contribution of kinetics and detailed physical mechanism to such categorization is not generally available except in some wellcharacterized situations, namely clathrin-pit endocytosis or endocytosis by actin-dependent forces in yeast. cache = ./cache/cord-329448-kxxy60x9.txt txt = ./txt/cord-329448-kxxy60x9.txt === reduce.pl bib === id = cord-333089-ufyzqgqk author = Aguilar-Pineda, Jorge Alberto title = Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry date = 2020-07-29 pages = extension = .txt mime = text/plain words = 6957 sentences = 359 flesch = 51 summary = Based on the structural complementarity and steric impediments between the S protein and human ACE2 (hACE2) protein membranes, we mapped the glycosylation sites of both models [21] [22] [23] [24] and performed molecular dynamics simulations (MDS) by 250 ns to stabilize the glycosylated SARS-CoV2 spike (S) and hACE2 complex (suppl. Given the possibility that occupancy at glycosylated residues or S-RBD binding sites by estrogens could modify the affinity of the SARS-CoV2 virus and alter entry into the cell thereby reducing infectivity, we sought to further examine these interactions using a range of complementary experimental approaches (see Table S1 ). In an effort to explore the potential protective effects of female sex hormones against SARS-CoV-2 infection, we examined the impact of estradiol (17β-diol) and a dietary-derived phytoestrogen (S-equol) on hACE2 structure and protein expression by a combination of in silico modeling, in vitro, and in vivo analysis. cache = ./cache/cord-333089-ufyzqgqk.txt txt = ./txt/cord-333089-ufyzqgqk.txt === reduce.pl bib === id = cord-338980-pygykil7 author = Rahaman, Jordon title = Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses date = 2016-11-09 pages = extension = .txt mime = text/plain words = 5801 sentences = 308 flesch = 52 summary = Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. For the DISOPRED2 predictions that were inferred using the nr database, the continuous disorder propensities for every site in a protein were mapped onto their corresponding position in the multiple sequence alignment as raw disorder propensities and as binary states, order or disorder, using a cutoff of 5. For regions with five or more consecutive sites that were 100% conserved in sequence across 1) all CoV or 2) across the MERS and SARS clades, the information of structural disorder prediction from IUPred and DISOPRED2 was used to identify all ungapped sites that were consistently predicted to have 100% conserved order. cache = ./cache/cord-338980-pygykil7.txt txt = ./txt/cord-338980-pygykil7.txt === reduce.pl bib === id = cord-340746-icuzy3vp author = Liang, Yunfei title = Comprehensive Antibody Epitope Mapping of the Nucleocapsid Protein of Severe Acute Respiratory Syndrome (SARS) Coronavirus: Insight into the Humoral Immunity of SARS date = 2005-08-01 pages = extension = .txt mime = text/plain words = 8408 sentences = 374 flesch = 47 summary = We identified the immunodominant antigenic sites responsible for the antibodies in sera from SARS patients and antisera from small animals and differentiated the linear from the conformational antibody-combining sites comprising the natural epitopes by use of yeast surface display. The full-length SARS-CoV N protein (amino acids 1-422) was expressed on the yeast cell surface, as indicated by reactivity of the Xpress epitope tag with the anti-Xpress antibody (Fig. 2) . We used heat denaturation of the fusion proteins tethered to the EBY100 yeast cell surface to categorize the specific linear and conformational SARS-CoV N protein mAb epitopes (35, 36 ) . Our subsequent determination of the antigenic structures of the N protein responsible for antibodies in polyclonal antisera from immunized mice and sera from convalescent SARS patients demonstrated the immunogenic specificity of 3 conformational (amino acids 1-69, 68 -213, and 337-422) and 3 linear (amino acids 1-69, 121-213, and 337-422) epitopes (Fig. 1C) . cache = ./cache/cord-340746-icuzy3vp.txt txt = ./txt/cord-340746-icuzy3vp.txt === reduce.pl bib === id = cord-329403-jzrlywfe author = Teo, Su Hui Catherine title = A NS1-binding monoclonal antibody interacts with two residues that are highly conserved in seasonal as well as newly emerged influenza A virus date = 2019-03-06 pages = extension = .txt mime = text/plain words = 4448 sentences = 246 flesch = 57 summary = In this study, we have generated a novel monoclonal antibody (mAb) 19H9 and epitope mapping revealed that two residues, P85 and Y89, of NS1 are essential for interacting with this mAb. Furthermore, residues P85 and Y89 are found to be highly conserved across different IAV subtypes, namely seasonal H1N1 and H3N2, as well as the highly pathogenic H5N1 and H5N6 avian strains. The membrane was then washed and full-length NS1 transfected cell lysates were subjected to IP with mAb 19H9 and protein A agarose beads followed by detection of immunoprecipitated proteins using rabbit anti-Myc antibody in Western blot. To delineate the epitope of NS1 recognized by mAb 19H9, a series of NS1 truncation mutants consisting of residues 1-84, 1-100, 91-230 and 85-230 were generated and their expression levels in transiently transfected 293T cells were verified using an anti-Myc antibody ( Fig. 2A, upper panel) . cache = ./cache/cord-329403-jzrlywfe.txt txt = ./txt/cord-329403-jzrlywfe.txt === reduce.pl bib === id = cord-333966-st6gyozv author = Taherkhani, Reza title = Design and production of a multiepitope construct derived from hepatitis E virus capsid protein date = 2015-03-17 pages = extension = .txt mime = text/plain words = 5199 sentences = 255 flesch = 51 summary = The aim of this study was to design a high density multiepitope protein, which can be a promising multiepitope vaccine candidate against Hepatitis E virus (HEV). Therefore, the present study was undertaken to design a high density multiepitope protein compromising four HTL epitopes with high-affinity binding to the HLA molecules using the in silico analysis, and to evaluate the immunological properties of this protein in vitro. In brief, approximately 1 Â 10 5 cells/well of PBMCs of each sample in RPMI 1640 and 10% FCS were added to four wells of round-bottom 96-well plates in total volume of 180 ml/well, stimulated with 20 ml/well of truncated ORF2 protein (10 mg/ml), high density multiepitope (10 mg/ml) and Phytohemagglutinin (PHA) (5 mg/ml) (Sigma-Aldrich) separately, and incubated at 37˚C for 4 days. IFN-g ELISPOT responses to high density multiepitope protein and truncated ORF2 protein were found significantly higher in HEV-recovered individuals than control group (P < 0.001). cache = ./cache/cord-333966-st6gyozv.txt txt = ./txt/cord-333966-st6gyozv.txt === reduce.pl bib === id = cord-346819-11fkgzaa author = Khan, Mohd Imran title = Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date = 2020-09-03 pages = extension = .txt mime = text/plain words = 4405 sentences = 291 flesch = 57 summary = title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. The genome analysis of the SARS-CoV-2 strains from 13 different countries showed a large number of mutations within the major structural proteins. This study provides a deeper insight into the emergence of these mutations within the major structural as well as nsp encoded by the SARS-CoV-2 genome from different countries. Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations backbone RMSD was also noticed (Fig 4A) . cache = ./cache/cord-346819-11fkgzaa.txt txt = ./txt/cord-346819-11fkgzaa.txt === reduce.pl bib === id = cord-322955-7dw32xby author = Kathwate, Gunderao H title = In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins date = 2020-06-12 pages = extension = .txt mime = text/plain words = 5729 sentences = 392 flesch = 47 summary = title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Those properties are calculated by different methods at IEDB server (http://tools.iedb.org/bcell/ )like Kolaskar-Tongaonkar antigenicity scale provide physiology of the amino acid residues(45), Emini Surface accessible score for accessible surface of the epitope(46), Secondary structure of epitopes also has role in antigenicity. High scored and common peptides predicted by various tools were selected for deriving sequence of potential vaccine candidate. We designed a multi-epitopes vaccine construct from S-protein of SARS-CoV2. From various epitopes predicted by the online server based on common sequence and high score three TCR and two BCR epitopes were selected as part of COVID19 vaccine. This vaccine codes epitopes form S protein of SARS-CoV2 virus for T and B cell receptors. cache = ./cache/cord-322955-7dw32xby.txt txt = ./txt/cord-322955-7dw32xby.txt === reduce.pl bib === id = cord-342189-ya05m58o author = Banerjee, Abhik K. title = SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses date = 2020-10-08 pages = extension = .txt mime = text/plain words = 11469 sentences = 647 flesch = 55 summary = Here, we comprehensively define the interactions between each SARS-CoV-2 protein and human RNAs. We show that 10 viral proteins form highly specific interactions with mRNAs or ncRNAs, including those involved in progressive steps of host cell protein production. We show J o u r n a l P r e -p r o o f 5 that NSP16 binds to the mRNA recognition domains of the U1 and U2 RNA components of the spliceosome and acts to suppress global mRNA splicing in SARS-CoV-2-infected human cells. We identified several pathogenic functions of SARS-CoV-2 in human cells -including global inhibition of host mRNA splicing, protein translation, and membrane protein trafficking -and described the molecular mechanisms by which the virus acts to disrupt these essential cell processes. cache = ./cache/cord-342189-ya05m58o.txt txt = ./txt/cord-342189-ya05m58o.txt === reduce.pl bib === id = cord-334592-54dofkxh author = Levine, Beth title = Autophagy in immunity and inflammation date = 2011-01-20 pages = extension = .txt mime = text/plain words = 10249 sentences = 418 flesch = 29 summary = Moreover, p62 is required for starvation and IFN-γ-induced targeting of Fau (and perhaps other ubiquitylated protein complexes) to mycobacteria-containing phagosomes, resulting in the generation of antimycobacterial Fau-derived peptides 42 .The role of p62 in innate immunity is probably evolutionarily ancient, as the Drosophila p62 orthologue REF(2)P was originally identified in a screen for modifiers of sigma virus replication 43 . The mechanisms by which autophagy genes mediate in vivo resistance to infection are not fully understood, but are likely to involve a combination of xenophagy, other autophagy-protein-dependent effects on microbial replication or survival, activation of innate and adaptive immune responses, and/or alterations in pathogen-induced cell death (Fig. 3 ). cache = ./cache/cord-334592-54dofkxh.txt txt = ./txt/cord-334592-54dofkxh.txt === reduce.pl bib === id = cord-333757-h12aozg2 author = Modis, Yorgo title = Class II Fusion Proteins date = 2013-07-10 pages = extension = .txt mime = text/plain words = 6790 sentences = 393 flesch = 51 summary = Furthermore, all available crystal structures of class II fusion proteins lack the 'stem' region, 43 a 30-55 amino acid linker between Domain III and the C-terminal transmembrane anchor (Figs. The three-dimensional structures of four class II fusion proteins in their postfusion states 29,55,56,94 reveal striking differences from the prefusion forms (Fig. 3) , and suggest a 13 and B) two SFV E1 12 molecules in the prefusion conformation as found on the viral surface, viewed perpendicular to the viral membrane. 29, 55 A deep channel extends from the C-terminus of the crystallized fragment along the intersubunit contact between domains II to the fusion loops, in both the dengue and Semliki Forest virus postfusion trimer structures. The recently determined crystal structures of class II fusion proteins in pre 10,12-14 and postfusion 29, 55, 56 conformations offer the first direct views of fusion anchors-in this case, the fusion loops-as they insert into a target membrane (Fig. 4) . cache = ./cache/cord-333757-h12aozg2.txt txt = ./txt/cord-333757-h12aozg2.txt === reduce.pl bib === id = cord-342639-vf9n2vf9 author = Chang, Chung-ke title = Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging date = 2013-05-23 pages = extension = .txt mime = text/plain words = 5386 sentences = 243 flesch = 42 summary = For disulfide trapping experiments, we chose mutation sites that would form disulfide linkages based on the crystal packing structures of the SARS-CoV N protein CTD ( Figure 1 ) [9] . Within the crystal asymmetric unit, the SARS-CoV N protein CTD packs as an octamer which stacks to form a helical arrangement with a continuous positively charged surface that could potentially allow the RNA to bind to it through electrostatic interactions ( Fig. 1 ) [9] . By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that SARS-CoV N protein is capable of transient oligomerization in solution through the CTD in the absence of nucleic acids. Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA cache = ./cache/cord-342639-vf9n2vf9.txt txt = ./txt/cord-342639-vf9n2vf9.txt === reduce.pl bib === id = cord-332784-xkc89uaz author = Mishra, Shashank Shekhar title = Computational investigation of potential inhibitors of novel coronavirus 2019 through structure-based virtual screening, molecular dynamics and density functional theory studies date = 2020-07-15 pages = extension = .txt mime = text/plain words = 4245 sentences = 234 flesch = 49 summary = The novel hit molecules identified from docking study were selected based on the docking score, binding energy calculations, and their other interactions with amino acid residues. To analyze the structural stability of the COVID-19 main protease protein-ligand complexes, molecular dynamics simulations were carried out by using Desmond in the presence of the POPC bilayer membrane (Shekhar et al., 2019) . The selected five potential hit molecules in the binding site of protease protein, interacting with amino acid residues Phe140, Gly143, Thr26, Thr190, Glu166, Pro168, Met165 and Leu141 with a docking score of À7.524 and À6.711 kcal/mol. It is found that the hydrogen bonds with Glu166 and hydrophobic interactions with Pro168, Leu167, Met 49, His41are major contributing factor for stabilizing hit molecule ZINC13144609 at the binding site which is in accordance with our docking result. cache = ./cache/cord-332784-xkc89uaz.txt txt = ./txt/cord-332784-xkc89uaz.txt === reduce.pl bib === id = cord-335915-2apj4qy9 author = Melillo, Alessandro title = Applications of Serum Protein Electrophoresis in Exotic Pet Medicine date = 2013-01-22 pages = extension = .txt mime = text/plain words = 5404 sentences = 225 flesch = 43 summary = The main difference between the 2 products is the absence in the serum of fribrinogen, the protein involved in the processes of coagulation; the concentration of total solids of the plasma is thus slightly higher than that of serum (about 5%) and the electrophoretic pattern from it will result in a higher incidence of b-globulin fraction where the fibrinogen normally migrates. In rabbits, the normal Serum Protein Electrophoresis (SPE) pattern lacks a clear distinction between b1-globulins and b2-globulins, as present in dogs and cats, but when gammopathies in the b region occur, usually an extension of the electrophoretic band is seen, with consequent demarcation of the 2 peaks. The first studies of serum proteins in birds were performed on domestic chickens, showing many similarities with the layout of mammals (eg, the production of APPs 18, 19 ), but also several differences: the widespread presence of prealbumin, for example, the lowest concentration of g-globulin, and conversely the more marked response to inflammatory stimuli in the b-globulin field. cache = ./cache/cord-335915-2apj4qy9.txt txt = ./txt/cord-335915-2apj4qy9.txt === reduce.pl bib === id = cord-345088-krb1eidw author = Shen, S title = A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature date = 2004-09-01 pages = extension = .txt mime = text/plain words = 6949 sentences = 316 flesch = 56 summary = title: A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature Here, we report the emergence and isolation of two temperature sensitive (ts) mutants and a revertant in the process of cold-adaptation of coronavirus infectious bronchitis virus (IBV) to a monkey kidney cell line. Evidence presented demonstrated that the Q(294)-to-L(294) mutation, located at a highly conserved domain of the S1 subunit, might hamper processing of the S protein to a matured 180-kDa, endo-glycosidase H-resistant glycoprotein and the translocation of the protein to the cell surface. In virus-infected cells, the Endo-H sensitive, 155-kDa form of ts291602 was abundant at the nonpermissive temperature, clearly indicating that the mutant S protein was trimmed in the ER and cis-Golgi but was not transported to the trans-Golgi. cache = ./cache/cord-345088-krb1eidw.txt txt = ./txt/cord-345088-krb1eidw.txt === reduce.pl bib === id = cord-336542-6asieplk author = Tanco, Sebastián title = Structure–Function Analysis of the Short Splicing Variant Carboxypeptidase Encoded by Drosophila melanogaster silver date = 2010-08-20 pages = extension = .txt mime = text/plain words = 7625 sentences = 431 flesch = 56 summary = Overall, DmCPD1Bs conforms to the structure of N/E-type funnelins/M14B metallopeptidases, but it has two unique structural elements potentially involved in regulation of its activity: (i) two contiguous surface cysteines that may become palmitoylated and target the enzyme to membranes, thus providing control through localization, and (ii) a surface hot spot targetable by peptidases that would provide a regulatory mechanism through proteolytic inactivation. Given that the fruit fly possesses orthologs of only two out of the five proteolytically competent N/E-type funnelins found in higher vertebrates, DmCPD1Bs may represent a functional analog of at least one of the missing mammalian CPs. The silver (svr) gene was discovered in Drosophila melanogaster by Bridges in the early 1920s and it maps near the distal end of chromosome X. [3] [4] [5] [6] The long variants possess the overall modular structure and sequence features of carboxypeptidase D (CPD), a glycosylated 180-kDa enzyme studied since the middle 1990s in fruit fly, mouse, rat, duck, bovine, chicken, and humans. cache = ./cache/cord-336542-6asieplk.txt txt = ./txt/cord-336542-6asieplk.txt === reduce.pl bib === id = cord-350286-n7ylgqfu author = Giri, Rajanish title = When Darkness Becomes a Ray of Light in the Dark Times: Understanding the COVID-19 via the Comparative Analysis of the Dark Proteomes of SARS-CoV-2, Human SARS and Bat SARS-Like Coronaviruses date = 2020-04-03 pages = extension = .txt mime = text/plain words = 15827 sentences = 874 flesch = 56 summary = The results of this analysis are summarized in Table 2 , which clearly shows that most of the SARS-CoV-2 proteins contain at least one MoRF, indicating that disorder does play an important role in the functionality of these viral proteins. As it follows from Figure 3 , these cleavage sites are located within the IDPRs. In Human SARS CoV S protein, fusion peptide (residues 770-788) is located within a flexible region, is characterized by the mean disorder score of 0.232±0.053. Global analysis of intrinsic disorder in the replicase polyprotein 1ab Table 3 represents the PPID mean scores of 15 non-structural proteins (Nsps) derived from the Replicase polyprotein 1ab in SARS-CoV-2, Human SARS CoV, and Bat CoV. Similar to many other non-structural proteins of coronaviruses, Nsp15s from SARS-CoV-2, Human SARS, and Bat CoV are predicted to possess multiple flexible regions but contain virtually no IDPRs (see Figures 32A, 32B, and 32C) . cache = ./cache/cord-350286-n7ylgqfu.txt txt = ./txt/cord-350286-n7ylgqfu.txt === reduce.pl bib === id = cord-339333-7tpnbr8q author = CHEN, YUXIAN title = Comparative serum proteome expression of the steroid-induced femoral head osteonecrosis in adults date = 2014-11-12 pages = extension = .txt mime = text/plain words = 3615 sentences = 211 flesch = 47 summary = The differentially-expressed protein spots were subjected to in-gel trypsin digestion followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The purpose of the present study is to find potential biomarkers of the SONFH by using proteomic technology to analyze serum protein profiles in patients with SONFH and the healthy control group. To ensure the reproducibility, accuracy and objectivity of the experiments, the following steps were Differentially-expressed protein spots were identified from the two-dimensional difference gel electrophoresis profiling of human plasma, with a lower abundance in the steroid-induced femoral head osteonecrosis group compared to the control group. In the present study, four proteins (C3, C4, ITIH4 and A2MG) showed lower expression in the serum of patients with SONFH than that of the normal subjects. The present study shows that the expression of C3, C4, ITIH4 and A2MG were significantly altered in patients with SONFH. cache = ./cache/cord-339333-7tpnbr8q.txt txt = ./txt/cord-339333-7tpnbr8q.txt === reduce.pl bib === id = cord-350558-qfdp4ov9 author = Shaban, Mohammed Samer title = Inhibiting coronavirus replication in cultured cells by chemical ER stress date = 2020-08-26 pages = extension = .txt mime = text/plain words = 5077 sentences = 297 flesch = 58 summary = We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. A detailed proteomics analysis reveals multiple thapsigargin-78 regulated pathways and a network of proteins that are suppressed by CoV but (re)activated by 79 chemically stressed infected cells. we determined the expression levels of 166 components of the ER stress pathway KEGG 04141 85 "protein processing in endoplasmic reticulum" in human HuH7 liver cells, a commonly used cellular 86 model for CoV replication, in response to infections with HCoV-229E and MERS-CoV, respectively. The highly inducible HERPUD1 protein has an essential scaffolding function for the organization of searching our proteomics data for further ERAD factors we were able to retrieve a total of 34 (for 284 MERS-CoV) and 20 (for SARS-CoV-2) proteins of the canonical ERQC and ERAD pathways for 285 which a differential expression was observed in virus-infected cells treated with thapsigargin (Fig. 286 5H) . cache = ./cache/cord-350558-qfdp4ov9.txt txt = ./txt/cord-350558-qfdp4ov9.txt === reduce.pl bib === id = cord-335310-61wibso4 author = Chen, Hui-Wen title = Synthetic virus-like particles prepared via protein corona formation enable effective vaccination in an avian model of coronavirus infection date = 2016-08-15 pages = extension = .txt mime = text/plain words = 5482 sentences = 264 flesch = 40 summary = Herein, a facile approach to formulate synthetic virus-like particles (sVLPs) is demonstrated by exploiting the phenomenon of protein corona formation induced by the high-energy surfaces of synthetic nanoparticles. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms in an avian model of coronavirus infection. Comparison to a commercial whole inactivated virus vaccine also showed evidence of superior antiviral protection by the sVLPs. The study demonstrates a simple yet robust method in bridging viral antigens with synthetic nanoparticles for improved vaccine application; it has practical implications in the management of human viral infections as well as in animal agriculture. In the present study, vaccination with the sVLPs resulted in enhanced humoral and cellular immune responses, improving protection against an avian model of coronavirus infection as compared to free protein antigens and a commercial WIV vaccine. cache = ./cache/cord-335310-61wibso4.txt txt = ./txt/cord-335310-61wibso4.txt === reduce.pl bib === id = cord-350309-j4oh1z8m author = Liu, D. X. title = Coronavirus envelope protein: A small membrane protein with multiple functions date = 2007-05-29 pages = extension = .txt mime = text/plain words = 3403 sentences = 167 flesch = 48 summary = The E proteins from infectious bronchitis virus (IBV) and mouse hepatitis virus (MHV) are translated from the third and second ORFs of mRNA 3 and 5 of the respective viruses by a cap-independent, internal ribosomal entry mechanism [6] [7] [8] [9] [10] [11] [12] . This modification is unique to SARS-CoV E protein, and it is still unknown whether the modification can also be detected in virus-infected cells and in virions. However, the membrane topologies of SARS-CoV E protein in virions and in virusinfected cells are still unknown. Similar to other viroporins [46] , expression of SARS-CoV and MHV E protein enhanced the membrane permeability of bacterial and mammalian cells [47, 48] . These results indicate that the ion channel activity of coronavirus E protein is important for virus replication, especially in the case of some coronaviruses, such as MHV. Biochemical evidence for the presence of mixed membrane topologies of the severe acute respiratory syndrome coronavirus envelope protein expressed in mammalian cells cache = ./cache/cord-350309-j4oh1z8m.txt txt = ./txt/cord-350309-j4oh1z8m.txt === reduce.pl bib === id = cord-339558-li65qvq9 author = Rana, Rashmi title = A comprehensive overview of proteomics approach for COVID 19: new perspectives in target therapy strategies date = 2020-11-02 pages = extension = .txt mime = text/plain words = 5934 sentences = 334 flesch = 44 summary = Structural proteome analysis of earlier SARS epidemic in 2003 revealed a large array of proteins that could be targeted for this pandemic too. They used affinity purification followed by mass spectrometry analysis and statistical modeling of the MS1level quantitative data which allowed the identification of 1484 interactions between 1086 cellular proteins and 24 SARS-CoV bait proteins. 2013 ) A recently published study involves the development of an Opto-microfluidic sensing platform to rapidly detect antibodies against SARS-CoV2 spike protein in diluted human plasma with high sensitivity. It is the first study to detect the SARS-CoV-2 antigens in the blood plasma of COVID-19-positive patients. Mass spectrometric identification of SARS-CoV-2 proteins from gargle solution samples of COVID-19 patients Development of mass spectrometry-based targeted assay for direct detection of novel SARS-CoV-2 coronavirus from clinical specimens A rapid and sensitive method to detect SARS-CoV-2 virus using targeted-mass spectrometry cache = ./cache/cord-339558-li65qvq9.txt txt = ./txt/cord-339558-li65qvq9.txt === reduce.pl bib === id = cord-350423-yaeduwvb author = James, Claire D. title = Viral Interactions with PDZ Domain-Containing Proteins—An Oncogenic Trait? date = 2016-01-18 pages = extension = .txt mime = text/plain words = 10615 sentences = 433 flesch = 39 summary = Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ) interaction modules. Survival of rabies infected neuronal cells is associated with the ability of the viral envelope G protein to interact with the PDZ domain-containing serine threonine kinase MAST2, leading to the disruption of the MAST2-PTEN complex that is intimately involved in the inhibition of neuronal survival [11] . Therefore, in HPV infections the tumour suppressor forms of DLG that are involved in the negative regulation of cell proliferation might be the initial target of the E6 PBM, but during disease progression DLG1, either through mislocalization and/or the stabilization of specific pools, acquires oncogenic functions mediated by interaction with E6 [3, 127] . cache = ./cache/cord-350423-yaeduwvb.txt txt = ./txt/cord-350423-yaeduwvb.txt === reduce.pl bib === id = cord-340387-ohkjheat author = Wynne, James W. title = Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA date = 2013-01-07 pages = extension = .txt mime = text/plain words = 7004 sentences = 390 flesch = 52 summary = title: Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. Considering that in other mammalian species, immunoglobulins IgG, IgM and IgA are present in relatively high abundance in serum and tissues, we anticipated that bats would possess a similar immunoglobulin profile. IgG-depleted samples were fractionated by affinity chromatography on immobilised anti-Fab-specific antibodies adopting the same procedure as that described for immobilised Protein A and G except that the binding and washing buffer consisted of 0.3 M NaCl in 50 mM phosphate buffer, pH 7.4. Two major bands were detected by reducing SDS-PAGE in the eluate from both serum and plasma samples; a 66-70 kDa band representative of IgM H , and a 25 kDa band representative of immunoglobulin light chain ( Fig. 3A and 3B ). cache = ./cache/cord-340387-ohkjheat.txt txt = ./txt/cord-340387-ohkjheat.txt === reduce.pl bib === id = cord-334220-sqvfr31q author = Messina, Francesco title = Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date = 2020-11-03 pages = extension = .txt mime = text/plain words = 4218 sentences = 237 flesch = 44 summary = The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. In SFigure For KEGG database the gene enrichment analysis on interactomes of NS7b, ORF1a, ORF3a and ORF8 showed pathway clusters highly significant and consistent with possible pathogenic mechanisms, such as the activation of the complement and of the coagulative cascade, (29) and the TGF-β-dominated immune response (30) . We identified different host response induced by specific proteins of SARS-CoV-2, underlining the important role of ORF3a and ORF8 in phenotypes of severe COVID-19 patients. cache = ./cache/cord-334220-sqvfr31q.txt txt = ./txt/cord-334220-sqvfr31q.txt === reduce.pl bib === id = cord-338468-c0jv3i1t author = Kanduc, Darja title = From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry date = 2020-07-16 pages = extension = .txt mime = text/plain words = 4143 sentences = 234 flesch = 41 summary = Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. In the wake of such results, in order to validate (or, as well, invalidate) the cross-reactivity hypothesis, investigation was expanded here by analyzing the peptide sharing between the human host and immunoreactive epitopes that are also present in SARS-CoV-2. Table 2 documents that numerous immunoreactive SARS-CoV-2 epitopes are composed mostly or, in many instances, uniquely of peptide sequences shared with human proteins. This study shows that hexapeptides from immunoreactive epitopes present in SARS-CoV-2 are widespread among a high number of human proteins. Table S2 : Hexapeptide sharing between 233 epitopes present in SARS-CoV-2 and human proteins. Table S3 : List and short description of 460 human proteins that share hexapeptides with the 233 SARS-CoV-2 epitopes. cache = ./cache/cord-338468-c0jv3i1t.txt txt = ./txt/cord-338468-c0jv3i1t.txt === reduce.pl bib === id = cord-337067-j8ebslif author = Mades, Andreas title = Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins date = 2012-11-15 pages = extension = .txt mime = text/plain words = 8726 sentences = 459 flesch = 48 summary = The overexpression of Sec63 reduces the steady-state levels of viral and cellular multi-spanning membrane proteins in a cotranslational mode, while soluble and single-spanning ER reporters are not affected. The specific action of Sec63 is further sustained by our observations that the up-regulation of either Sec62 or two other ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the steady-state level of a multi-spanning membrane reporter. Similar results were obtained with cell lysates prepared with the denaturing detergent SDS (Fig. 1B) , indicating that the observed down-regulation of HBV.S by excess Sec63 was not merely due to changes in the solubility profile. To analyze whether an up-regulation of these ERdj proteins might also affect the level of a multi-spanning membrane protein, FLAG-tagged versions of ERdj1 and ERdj4 were cotransfected with HBV.S. FLAG-specific Western blotting confirmed the ectopic expression of ERdj1 and ERdj4 in 63 and 25 kDa forms, respectively, consistent with their theoretical molecular masses (Fig. 9) . cache = ./cache/cord-337067-j8ebslif.txt txt = ./txt/cord-337067-j8ebslif.txt === reduce.pl bib === id = cord-356019-k7gs1ohp author = Makhzoum, Abdullah title = Recent advances on host plants and expression cassettes' structure and function in plant molecular pharming date = 2013-08-20 pages = extension = .txt mime = text/plain words = 8923 sentences = 405 flesch = 40 summary = As molecular pharming platforms, plants are excellent biofactories for the production of drugs, antibodies, and vaccines in various host systems such as whole transgenic plants, cell suspension culture, hairy roots, and hydroponic culture [1] [2] [3] . Here, we review these aspects and report recent advances in the improvements of plant molecular pharming to increase protein yield and accumulation based on upstream and downstream processing studies and empirical essays. In addition to the importance of promoter architecture for gene expression in molecular pharming, other strategies based on using specific peptides at N-and C-termini have been employed to enhance the transcript level of recombinant proteins. For example, the production and accumulation of the recombinant human granulocyte colony-stimulating factor was significantly increased in transgenic rice suspension culture by an RNAi approach designed to suppress the cysteine proteinase gene expression or by the inhibition of proteinase [104, 105] . cache = ./cache/cord-356019-k7gs1ohp.txt txt = ./txt/cord-356019-k7gs1ohp.txt === reduce.pl bib === id = cord-341129-eo0vjcmk author = Kielian, Margaret title = Virus membrane-fusion proteins: more than one way to make a hairpin date = 2006 pages = extension = .txt mime = text/plain words = 6986 sentences = 333 flesch = 45 summary = Virus membrane-fusion proteins drive the fusion reaction by undergoing a major conformational change that is triggered by interactions with the target cell. The class I membrane-fusion reaction is mediated by the refolding of the fusion protein to a highly stable rod-like structure with a central trimeric α-helical coiled coil. In vitro studies using the ectodomains of both the alphavirus and flavivirus proteins showed that trimerization requires insertion of the fusion peptide into target membranes 64, 65 . However, H230A virus undergoes apparently normal conformational changes upon exposure to low pH, including heterodimer dissociation and fusion-loop exposure, cholesterol-dependent target-membrane insertion, and formation of the E1 homotrimer. Recent work indicates that exogenous domain III blocks class II membrane fusion and infection by binding to the fusion protein during the low-pH-induced conformational change 92 . cache = ./cache/cord-341129-eo0vjcmk.txt txt = ./txt/cord-341129-eo0vjcmk.txt === reduce.pl bib === id = cord-334511-lx9608vy author = Emwas, Abdul-Hamid title = NMR as a “Gold Standard” Method in Drug Design and Discovery date = 2020-10-09 pages = extension = .txt mime = text/plain words = 29224 sentences = 1507 flesch = 47 summary = The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . Clearly, combining virtual screening with NMR-based methods is advantageous in studying how ligands (drugs) bind and interact with targets (proteins) of interest. The interactions between targets (proteins) and ligands (small molecules) can be analyzed independently of the biological systems by using 'cell-based' NMR drug design approaches. cache = ./cache/cord-334511-lx9608vy.txt txt = ./txt/cord-334511-lx9608vy.txt === reduce.pl bib === id = cord-336119-8g37xsys author = Nimgampalle, Mallikarjuna title = Screening of Chloroquine, Hydroxychloroquine and its derivatives for their binding affinity to multiple SARS-CoV-2 protein drug targets date = 2020-06-24 pages = extension = .txt mime = text/plain words = 5464 sentences = 283 flesch = 50 summary = Our current study also shows that some of the chemically synthesized Chloroquine derivatives can also potentially inhibit various SARS-CoV-2 viral proteins by binding to them and concomitantly effectively disrupting the active site of these proteins. By using in-silico molecular docking studies, the binding potential of Chloroquine and its derivatives with different SARS-CoV-2 proteins involved in viral replication was evaluated. Based on the recent reports, some of the essential regulatory proteins and enzymes associated with the pathogenesis of SARS-CoV-2 were selected as drug targets such as the Spike glycoprotein that enables virus internalization, RNA dependent RNA polymerase that supports replication of viral genetic material, Chimeric RBD (Receptor binding domain) that interacts with the ACE 2, Main protease responsible for cleaving the viral polypeptide, Non-structural Protein3, Nonstructural Protein 10, Non-structural Protein 9 (Replicase Table 3 . cache = ./cache/cord-336119-8g37xsys.txt txt = ./txt/cord-336119-8g37xsys.txt === reduce.pl bib === id = cord-336364-2ust3qoq author = Artigas, Laura title = In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm date = 2020-10-02 pages = extension = .txt mime = text/plain words = 5858 sentences = 295 flesch = 45 summary = title: In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm This has provided 3 sets of proteins related with the infection process: 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lungcells infection set, and 3) acute respiratory distress (ARD) set. According to the findings by GUILDify, we confirm the effect of the combination of pirfenidone and melatonin in the entry points of the SARS-CoV-2 infection, specifically the neighbours of furin and GRP-78, and some proteins associated with ARD. 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lung-cells infection set, and 3) acute respiratory distress (ARD) set that is composed of 6 subsets (Alveolar macrophages, Monocytes, Neutrophils, Intermediate phase ARD, Late phase ARD and ARD cytokine storm). cache = ./cache/cord-336364-2ust3qoq.txt txt = ./txt/cord-336364-2ust3qoq.txt === reduce.pl bib === id = cord-342634-4ouhdjsr author = Semrad, Katharina title = Proteins with RNA Chaperone Activity: A World of Diverse Proteins with a Common Task—Impediment of RNA Misfolding date = 2010-12-26 pages = extension = .txt mime = text/plain words = 7141 sentences = 399 flesch = 52 summary = In brief, the group of proteins with RNA chaperone activity includes proteins that, first, open up misfolded structures without requirement of ATP and that, second, are dispensable once the RNA has been folded. coli showed that 1/3 of the tested proteins possesses strong RNA chaperone activity in vitro in the trans-splicing assay [21] . E. coli contains nine members of the csp family and CspA, the major cold-shock protein and CspE were identified to interact non-specifically with RNA molecules and to possess nucleic acid melting activities [44] [45] [46] . Later, a detailed study on possible functions of Ro RNPs, which are Ro ribonucleoprotein complexes, composed of a small noncoding cytoplasmic RNA, termed Y RNA and its protein partners was conducted: besides the permanently associated proteins Ro60 and La, subpopulations of Ro-RNPs also contain hnRNP I and hnRNP K, both of which exhibited strong RNA chaperone activity in vitro in the transsplicing and the cis-splicing assay [22] . cache = ./cache/cord-342634-4ouhdjsr.txt txt = ./txt/cord-342634-4ouhdjsr.txt === reduce.pl bib === id = cord-348360-20eq5meh author = Esposito, Dominic title = Optimizing high-yield production of SARS-CoV-2 soluble spike trimers for serology assays date = 2020-06-04 pages = extension = .txt mime = text/plain words = 3438 sentences = 158 flesch = 49 summary = To improve the yield of spike protein and support the high demand for antigens in serology assays, we investigated several recombinant protein expression variables by altering the incubation temperature, harvest time, chromatography strategy, and final protein manipulation. Thus, the work presented here is intended to provide a robust method for those wishing to reliably produce SARS CoV-2 spike protein in quantities sufficient for serology assays, structural biology, or simply to better understand some of the production variables affecting the yield. Nevertheless, the approaches outlined here allowed us to improve the production yield of spike protein significantly by modifying cell culture temperature and harvest time, as well as improving the purification process. To produce SARS-CoV-2 antigens for the development of serology assays, we initially followed standard procedures for secreted protein production: transfection using the manufacturer's protocols, expression at 37°C, harvest at three days post-transfection, tangential flow filtration of the culture supernatant, immobilized metal ion chromatography with linear gradient elution, and size exclusion chromatography. cache = ./cache/cord-348360-20eq5meh.txt txt = ./txt/cord-348360-20eq5meh.txt === reduce.pl bib === id = cord-354050-kcn67stj author = Shi, Guoli title = More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins date = 2017-11-21 pages = extension = .txt mime = text/plain words = 6846 sentences = 313 flesch = 36 summary = Most of what we know about the antiviral activities of IFITM proteins results from work using IAV and vesicular stomatitis virus (VSV), which perform pH-dependent fusion reactions in endosomes to gain access to the cell interior [22] . As the primary determinant for virus-cell attachment and the subsequent fusion reaction, the viral envelope glycoprotein (Env) was suspected to play an important role in whether or not HIV-1 and related lentiviruses are subject to inhibition by IFITM proteins. In addition to restricting virus entry, recent findings indicate that IFITM proteins perform antiviral functions impacting late stages of the HIV-1 life cycle. This antiviral activity is enhanced upon expression of an IFITM3 mutant that is defective for endocytosis, indicating that restriction of HIV-1 virion infectivity is performed at the plasma membrane [5] . Nonetheless, the recent identification of Env variants that are resistant to the IFITM3-mediated restriction of virion infectivity confirms this viral protein as an important determinant. cache = ./cache/cord-354050-kcn67stj.txt txt = ./txt/cord-354050-kcn67stj.txt === reduce.pl bib === id = cord-352371-t54zftal author = Kumar, Ravindra title = Prediction of endoplasmic reticulum resident proteins using fragmented amino acid composition and support vector machine date = 2017-09-04 pages = extension = .txt mime = text/plain words = 6606 sentences = 343 flesch = 54 summary = RESULTS: In this study, we have reported a novel support vector machine based method for predicting endoplasmic reticulum resident proteins, named as ERPred. But these have some shortcomings like (i) among the above mentioned predictors, none were designed specifically to predict ERRPs; (ii) datasets used for training for prediction model were very old; (iii) subcellular locations were determined for a particular organism or groups (plant/animal/viral); (iv) many of them do not provide webserver/standalone software for scientific purpose and if some of them does so, they are not in working condition. Using standalone version of ScanProsite (Gattiker, Gasteiger & Bairoch, 2002) , out of 124 proteins of training dataset, we were able to find ER retention signal ([KRHQSA]-[DENQ]-E-L) in only 66 proteins, which shows that signal sequence is not present in all ERRPs. This shows that signal based approach may not be appropriate for complete ERRP repertoire prediction of any proteome. cache = ./cache/cord-352371-t54zftal.txt txt = ./txt/cord-352371-t54zftal.txt === reduce.pl bib === id = cord-350935-p6euuop3 author = Doğan, Tunca title = CROssBAR: Comprehensive Resource of Biomedical Relations with Deep Learning Applications and Knowledge Graph Representations date = 2020-09-15 pages = extension = .txt mime = text/plain words = 7066 sentences = 298 flesch = 45 summary = We aimed to address this issue by constructing a new biological and biomedical data resource, CROssBAR, a comprehensive system that integrates large-scale biomedical data from various resources and store them in a new NoSQL database, enrich these data with deep-learning-based prediction of relations between numerous biomedical entities, rigorously analyse the enriched data to obtain biologically meaningful modules and display them to users via easy-to-interpret, interactive and heterogenous knowledge graph (KG) representations within an open access, user-friendly and online web-service at https://crossbar.kansil.org. In this project, we aimed to address the current shortcomings by developing a comprehensive open access biomedical system entitled CROssBAR via integrating various biological databases to each other, inferring the missing relations between existing data points, and constructing informative knowledge graphs based on specific biomedical components/terms such as a disease/phenotype, biological process, gene/protein and drug/compound, or specific combinations of them. cache = ./cache/cord-350935-p6euuop3.txt txt = ./txt/cord-350935-p6euuop3.txt === reduce.pl bib === id = cord-341378-pw60qx7c author = Armstrong, John title = Sequence and topology of a model intracellular membrane protein, E1 glycoprotein, from a coronavirus date = 1984 pages = extension = .txt mime = text/plain words = 1578 sentences = 88 flesch = 55 summary = In combination with a previous study of its assembly into the endoplasmic reticulum membrane(9), the sequence reveals several unusual features of the protein which may be related to its intracellular localization. In the eukaryotic cell, both secreted and plasma membrane proteins are synthesized at the endoplasmic reticulum, then transported, via the Golgi complex, to the ceU surface 1 -4. Here we present the primary structure of the protein, determined by analysis of eDNA clones prepared from viral mRNA. In combination with a previous stu'!} of its assembly into the endoplasmic reticulum membrane , the sequence reveals several unusual features of the protein which may be related to its intracellular localization. Thus, the El glycoprotein is potentially a convenient model for studying those features of a membrane protein that determine its arrest at a particular destination on the membrane transport pathway. cache = ./cache/cord-341378-pw60qx7c.txt txt = ./txt/cord-341378-pw60qx7c.txt === reduce.pl bib === id = cord-339091-3xk2w0d2 author = Flower, Darren R title = Computer aided selection of candidate vaccine antigens date = 2010-11-03 pages = extension = .txt mime = text/plain words = 10669 sentences = 558 flesch = 40 summary = The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. Initially, the pathogenic genome is scanned for "open reading frames" or ORFs. Once all ORFs have been identified, proteins are selected on the basis that they will be accessible to immune system surveillance, usually using some form of informatic-based prediction methodology or, more likely, set of methdologies. We shall below examine three key approaches: subcellular location prediction, sequence similarity, and empirical statistical approaches, typified by VaxiJen. For a protein to be accessible to surveillance by the immune system, it is often assumed to be physically external to the microbial organism or at least present on its surface rather than being sequestered away far from the roving eye of the immune system. cache = ./cache/cord-339091-3xk2w0d2.txt txt = ./txt/cord-339091-3xk2w0d2.txt === reduce.pl bib === id = cord-355327-d3gcfepx author = Fan, Samuel W title = Conformational changes in redox pairs of protein structures date = 2009-08-01 pages = extension = .txt mime = text/plain words = 9859 sentences = 544 flesch = 47 summary = Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. These groups were: proteins that oxidize disulfides following expulsion of metals such as Zn; proteins that exhibited major reorganization or ''morphing'' of portions of the polypeptide backbone in association with disulfide redox-activity; proteins that exhibited order/disorder transitions; and proteins that exhibited changes in quaternary structure. Twenty-nine Redox Pair protein clusters with intermolecular disulfide bonds exhibit changes in quaternary structure upon oxidation/reduction. We were previously aware of two instances where subdomain morphing of proteins has been associated with reversible disulfide reduction: a redox-controlled structural reorganization of the ion channel CLIC1 proposed to regulate its insertion into membranes, 18 and sequential oxidation of the transcription factor OxyR in response to oxidative stress which modulates its quaternary structure and DNA-binding properties. cache = ./cache/cord-355327-d3gcfepx.txt txt = ./txt/cord-355327-d3gcfepx.txt === reduce.pl bib === id = cord-342118-fsmuqktd author = Dyakov, Ilya N. title = FN3 protein fragment containing two type III fibronectin domains from B. longum GT15 binds to human tumor necrosis factor alpha in vitro date = 2020-08-06 pages = extension = .txt mime = text/plain words = 2445 sentences = 150 flesch = 57 summary = Previously, based on the analysis of the genomes of 34 species of bifidobacteria, we 233 identified and characterized a species-specific cluster of PFNA genes, which consists of To develop a sandwich ELISA assay that would allow us to check the ability of the 298 recombinant FN3 protein to bind human cytokines, we raised polyclonal antibodies 299 specific to the recombinant FN3 protein. The resulting affinity 302 purified and concentrated preparation contained 1 mg of FN3-specific rabbit polyclonal 303 antibodies per 1 mL and was highly active -specific interaction with the FN3 protein 304 was detected even after 1:820000 dilution. To exclude the possibility of blockage of the cytokine-binding motif of the FN3 335 protein and its nonspecific adsorption onto the solid surface, we employed ELISA 336 scheme 3 described in the materials and methods section: The FN3-specific rabbit 337 polyclonal antibodies were first adsorbed onto the solid surface after which the FN3 338 protein was added as a "second layer". cache = ./cache/cord-342118-fsmuqktd.txt txt = ./txt/cord-342118-fsmuqktd.txt === reduce.pl bib === id = cord-343791-0vykwml5 author = Hainline, Kelly M. title = Progress towards the clinical translation of bio-inspired peptide and protein assemblies date = 2017-11-08 pages = extension = .txt mime = text/plain words = 7314 sentences = 416 flesch = 42 summary = These include spherical assemblies such as virus-like particles, designed protein nanoparticles, and peptide amphiphiles (Figure 1) ; and elongated structures such as β-sheet nanofibers, fiber-forming peptide amphiphiles, and filamentous phage (Figure 2) . [17, 18] Owing to their lack of a viral genome, VLP-based vaccines circumvent some risks associated Supramolecular materials composed of proteins and peptides have been receiving considerable attention toward a range of diseases and conditions from vaccines to drug delivery. [19] As alternatives to these previous platforms, VLPs were developed to display an array of epitopes that mimic the surface of native viruses more effectively than subunit or peptide vaccines, thus improving their immunogenic properties. Whereas synthetic peptides are usually not sufficiently immunogenic and require adjuvants, the Burkhard group has developed a self-assembling protein nanoparticle platform that displays both B and T cell epitopes to produce a vaccine with self-adjuvanting qualities. cache = ./cache/cord-343791-0vykwml5.txt txt = ./txt/cord-343791-0vykwml5.txt === reduce.pl bib === id = cord-352172-g0jiaenw author = Stoevesandt, Oda title = Protein microarrays: high-throughput tools for proteomics date = 2014-01-09 pages = extension = .txt mime = text/plain words = 7464 sentences = 373 flesch = 32 summary = While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. Protein microarray technology has rapidly developed into one of the most active areas in biotechnology today, and is being increasingly applied for the high-throughput discovery of molecular interactions, profiling of protein expression and monitoring of protein modifications. While genome sequencing and annotations provide comprehensive information on protein-encoding genes, and DNA arrays analyze gene expression at the mRNA level, these technologies need to be complemented by functional proteomic studies in order to better understand protein activities, expression levels and interactions at the system level. A reverse-phase micro array approach has been successfully applied to discover distinct pathway-activation differences among breast cancer cell lines, demonstrating the use of array-based ana lysis for multiple pharmacodynamic biomarkers responding to targeted kinase inhibitors [108] . cache = ./cache/cord-352172-g0jiaenw.txt txt = ./txt/cord-352172-g0jiaenw.txt === reduce.pl bib === id = cord-355913-fhvt1ht1 author = Burrell, Christopher J. title = Virus Replication date = 2016-11-11 pages = extension = .txt mime = text/plain words = 9861 sentences = 405 flesch = 42 summary = Little is known about what determines whether a given picornavirus positive-sense RNA molecule will be directed (1) to a replication complex (a structure bound to smooth endoplasmic reticulum), where it serves as template for transcription by RNA-dependent RNA polymerase into negative-sense RNA, or (2) to a ribosome, where it serves as mRNA for translation into protein, or (3) to a procapsid, with which it associates to form a virion. In the case of positive-sense single-stranded RNA viruses, the incoming RNA genome can bind directly to ribosomes and be translated in full or in part without the need for any prior transcription; all other forms of incoming viral RNA must first be transcribed to produce mRNA, in order to begin the process of expression of the infecting viral genome. cache = ./cache/cord-355913-fhvt1ht1.txt txt = ./txt/cord-355913-fhvt1ht1.txt === reduce.pl bib === id = cord-337158-0iw2kcaf author = Tiernan, Hannah title = ATR-FTIR spectroscopy and spectroscopic imaging for the analysis of biopharmaceuticals date = 2020-06-22 pages = extension = .txt mime = text/plain words = 7405 sentences = 425 flesch = 38 summary = Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy is a label-free, non-destructive technique that can be applied to a vast range of biological applications, from imaging cancer tissues and live cells, to determining protein content and secondary structure composition. This characterisation commonly involves the use of techniques such as liquid chromatography tandem mass spectrometry (LC-MS-MS) to monitor changes in mass, 16 high pressure liquid chromatography (HPLC) to determine impurity profiles of samples, 17 and infrared spectroscopy (IR) to identify impurities and compare biosimilars to the original, 'reference drugs'. 75 ATR-FTIR spectroscopy has also been used extensively to study proteins, in particular biopharmaceuticals, and exciting research has shown the potential applications of it to investigate and monitor changes effectively in PTMs and secondary structures. For example, Grosshans et al used in-line FTIR spectroscopy, along with partial least squares (PLS) analysis, as an effective process analytical tool (PAT) for preparative protein chromatography, they found it to be useful to distinguish and selectively identify proteins based on their secondary structure. cache = ./cache/cord-337158-0iw2kcaf.txt txt = ./txt/cord-337158-0iw2kcaf.txt === reduce.pl bib === id = cord-341564-fvuwick5 author = Qi, Zhao-Hui title = Novel Method of 3-Dimensional Graphical Representation for Proteins and Its Application date = 2018-06-12 pages = extension = .txt mime = text/plain words = 2647 sentences = 178 flesch = 54 summary = From these, we can see that physicochemical properties are widely applied with graphical representation of protein sequences by these researchers and their results seem well. In this article, we propose a 3-dimensional (3D) graphic representation of protein sequences based on 10 physicochemical properties [17] [18] [19] [20] [21] of amino acids and the BLOSUM62 matrix. In this article, we propose a 3-dimensional (3D) graphic representation of protein sequences based on 10 physicochemical properties [17] [18] [19] [20] [21] of amino acids and the BLOSUM62 matrix. Therefore, to mine essential information from a protein sequence, we propose an effective graphical method combining physicochemical properties of amino acids and the BLOSUM62 matrix. An efficient numerical method for protein sequences similarity analysis based on a new two-dimensional graphical representation F-Curve, a graphical representation of protein sequences for similarity analysis based on physicochemical properties of amino acids cache = ./cache/cord-341564-fvuwick5.txt txt = ./txt/cord-341564-fvuwick5.txt === reduce.pl bib === id = cord-355477-7xd93aqv author = SATIJA, NAMITA title = The Molecular Biology of SARS Coronavirus date = 2007-04-23 pages = extension = .txt mime = text/plain words = 4946 sentences = 279 flesch = 52 summary = abstract: Severe acute respiratory syndrome (SARS) is the first emerging infectious disease of the 21st century that has been highly transmissible and fatal and was caused by a previously unknown coronavirus (SARS‐CoV). Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways Assembly of severe acute respiratory syndrome coronavirus RNA packaging signal into virus-like particles is nucleocapsid dependent Recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein forms a dimer through its C-terminal domain Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells cache = ./cache/cord-355477-7xd93aqv.txt txt = ./txt/cord-355477-7xd93aqv.txt === reduce.pl bib === id = cord-347714-vxxhglx7 author = Abitogun, Folagbade title = COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding date = 2020-10-14 pages = extension = .txt mime = text/plain words = 3707 sentences = 191 flesch = 44 summary = (10, 11) The structure of the spike glycoprotein of the virus is also an extended similarity with SARS-CoV, (4) which together with COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding other proteins of the virus are candidates for vaccine development and are being explored in different settings due to the active roles of the proteins in the infectivity of the virus. (18) However studies have shown that full length spike protein vaccines for SARS-CoV may lead to antibody mediated disease enhancement causing inflammatory and liver damage in animal models (19, 20) which is why in this manuscript, we applied immuno-informatics "in silico" approaches to identify potential CD8+ cytotoxic T Cell epitopes from proteins of SARS-CoV-2, SARS-CoV and MERS-CoV. Multi-epitope Based Peptide Vaccine Design Using Three Structural Proteins (S, E, and M) of SARS-CoV-2: An In Silico Approach cache = ./cache/cord-347714-vxxhglx7.txt txt = ./txt/cord-347714-vxxhglx7.txt === reduce.pl bib === id = cord-349774-898tmq14 author = Zhang, Haiyang title = Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein date = 2020-06-16 pages = extension = .txt mime = text/plain words = 3172 sentences = 188 flesch = 52 summary = title: Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein Here, we report for the first time that the 11S proteasomal activator PA28γ regulates the intracellular abundance of the SARS-CoV-2 N protein (nCoV N). These results suggest that PA28γ binding is important in regulating 20S proteasome activity, which in turn regulates levels of the critical nCoV N nucleocapsid protein of SARS-CoV-2, furthering our understanding of the pathogenesis of COVID-19. The SARS-CoV-2 nucleocapsid protein (hereafter, referred to as nCoV N) accounts for the largest proportion of viral structure proteins and is the most abundant protein in virus-infected cells. PA28γ could be critical for degrading the SARS-CoV-19 nCoV N protein in the nucleus as part of the 20S proteasome, which acts to degrade proteins in a ubiquitin-independent manner, such as seen in the hepatitis C virus (HCV) core protein [11] . Interactions of SARS Coronavirus Nucleocapsid Protein with the host cell proteasome subunit p42 cache = ./cache/cord-349774-898tmq14.txt txt = ./txt/cord-349774-898tmq14.txt === reduce.pl bib === id = cord-346314-o9fjpqaj author = Jarboui, Mohamed Ali title = Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus date = 2012-11-15 pages = extension = .txt mime = text/plain words = 10004 sentences = 521 flesch = 36 summary = Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. Following the detailed annotation of the quantitative abundance changes in the nucleolar protein composition upon Tat expression, we focussed on the Tat-affected cellular complexes and signalling pathways associated with ribosome biogenesis, spliceosome, molecular chaperones, DNA replication and repair and metabolism and discuss their potential involvement in HIV-1 pathogenesis. In this study, we investigated the quantitative changes in the nucleolar proteome of Jurkat T cells constitutively expressing HIV-1 Tat (86aa) versus their Tat-negative counterpart, using stable isotope labelling with amino acids in cell culture (SILAC) technology, followed by ESI tandem mass spectrometry and implemented the experimental approach described in Figure 1A . cache = ./cache/cord-346314-o9fjpqaj.txt txt = ./txt/cord-346314-o9fjpqaj.txt === reduce.pl bib === id = cord-345712-gmzue6lj author = Palazzo, Luca title = ADP‐ribosylation: new facets of an ancient modification date = 2017-04-26 pages = extension = .txt mime = text/plain words = 6641 sentences = 389 flesch = 42 summary = Altogether, ADPribosylation is a widespread modification that controls a vast number of cellular processes, including DNA damage repair, transcription, cell-cycle progression, cell division, unfolded protein response, aging, nitrogen fixation, microbial pathogenicity, cell death and many others [7, 14, [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] . As a consequence, macrodomain-containing proteins are involved in a diverse set of cellular functions, such as chromatin remodelling and DNA-damage repair, oxidative stress response, metabolic processes and pathogenic mechanisms [3,5,10-13,30,37, 53, 54, [59] [60] [61] . Studies looking either at the genomic context of ADPribosylating systems or their evolution in bacteria suggest that ADP-ribosylation might be involved in the regulation of many crucial cellular processes including bacterial persistence, oxidative stress response and adaptation to the host environment in general [5, 9, 49, 154] . cache = ./cache/cord-345712-gmzue6lj.txt txt = ./txt/cord-345712-gmzue6lj.txt === reduce.pl bib === id = cord-341701-zropd3mo author = Adhikari, Subash title = A high-stringency blueprint of the human proteome date = 2020-10-16 pages = extension = .txt mime = text/plain words = 10138 sentences = 533 flesch = 33 summary = During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. • Be a focal point for life sciences researchers, pathologists, clinicians and industry communities seeking to translate and leverage proteomic and proteogenomic data to improve human health through: (i) greater understanding of the molecular mechanisms of common and rare diseases, (ii) identification of pathophysiological changes to generate disease and wellness diagnostic biomarkers, and (iii) development of new effective and safe personalized therapeutics. The HPP Ab Resource Pillar, ostensibly led by the Human Protein Atlas (HPA; www.proteinatlas.org), was initiated in 2003 and uses Ab-based strategies to analyse spatio-temporal aspects of the proteome 39 . Community encouragement to identify biological data that complement high-stringency MS strategies to accelerate discovery and understanding of human proteome PE2,3,4 missing proteins. cache = ./cache/cord-341701-zropd3mo.txt txt = ./txt/cord-341701-zropd3mo.txt === reduce.pl bib === id = cord-347661-q9lgliph author = Zevenhoven-Dobbe, Jessika C. title = Production of Monospecific Rabbit Antisera Recognizing Nidovirus Proteins date = 2007-11-28 pages = extension = .txt mime = text/plain words = 6866 sentences = 343 flesch = 53 summary = The use as antigens of either synthetic peptides (coupled to a carrier protein) or proteins expressed in Escherichia coli is described, and detailed protocols for immunization and preparation of test bleeds are provided. Furthermore, in the context of specific research questions, polyclonal antisera may sometimes even be preferred over monoclonal antibodies since they contain a mixture of immunoglobulin molecules, derived from different B-cell lines in the immunized animal, often recognizing multiple epitopes of the target protein. The antiserum used here was raised against a domain in the C-terminal region of pp1a of the arterivirus EAV (8) and recognizes a large set of processing intermediates and end products, which are indicated by arrowheads: (A) Western blot analysis: EAV-and mock-infected cell lysates were prepared at 8 h postinfection, run on an SDS-polyacrylamide gel, blotted to PVDF membrane, and incubated with the postimmune serum at a 1:1000 dilution. cache = ./cache/cord-347661-q9lgliph.txt txt = ./txt/cord-347661-q9lgliph.txt === reduce.pl bib === id = cord-342756-rgm9ffpk author = Senger, Mario Roberto title = COVID-19: molecular targets, drug repurposing and new avenues for drug discovery date = 2020-10-02 pages = extension = .txt mime = text/plain words = 16108 sentences = 1024 flesch = 51 summary = Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. In the following topic, we will review SARS-CoV-2 structure and mechanism of infection in order to discuss molecular targets from the virus or its human host that are being considered for drug repurposing and perhaps future development of new drugs. (128) Its role as a functional receptor of SARS-CoV-2 S protein in host cells makes this protein a potential drug target to treat COVID-19. (138) TMPRSS2 has a major role in SARS-CoV-2 cell entry and replication, and thus represents an interesting therapeutic target since its inhibitors could potentially block virus infection in its initial stages. (199) A robust preclinical drug discovery pipeline comprising in vitro, and in vivo models of SARS-CoV-2 infection is particularly important to identify new antivirals for human COVID-19 treatment. cache = ./cache/cord-342756-rgm9ffpk.txt txt = ./txt/cord-342756-rgm9ffpk.txt === reduce.pl bib === id = cord-354030-8tfg881h author = Dong, Rong title = Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches date = 2020-07-28 pages = extension = .txt mime = text/plain words = 7983 sentences = 442 flesch = 52 summary = The realm of immunoinformatics tools considers the mechanism of the host immune response to yield additional methodologies in the design of vaccine against diseases are cost-effective and convenient, as in silico predictions can reduce the number of experiments needed (13, 14) . In this present, we employed immunoinformatics to predict multiple immunogenic proteins from the SARS-CoV-2 proteome and thereby design a multi-epitope vaccine. developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . A vaccine based on the spike protein could induce antibodies to block SARS-COV-2 binding and fusion or neutralize virus infection (18) , as well as induce harmful immune responses that cause liver damage (19) . To design an effective vaccine, we selected the SARS-CoV-2 protein through the above-mentioned methods for epitope prediction. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach cache = ./cache/cord-354030-8tfg881h.txt txt = ./txt/cord-354030-8tfg881h.txt === reduce.pl bib === id = cord-346965-0oq2n0af author = Liu, Zhi-Ping title = Bridging protein local structures and protein functions date = 2008-04-18 pages = extension = .txt mime = text/plain words = 14491 sentences = 810 flesch = 44 summary = The characteristics between interface and noninterface portions of a protein surface, such as sequence conservation, proportions of amino acids, secondary structure, solvent accessibility and side-chain conformational entropy, are often used to distinguish the specificity of local structures relating to protein binding function. The method relies on a simplified representation of the chemical groups found in amino acid side-chains to identify functional sites from a single protein structure and a number of its sequence homologs. (2006) improved previous approaches by combining two known measures of 'functionality' in proteins, i.e. cleft volume and residue conservation, to develop a method for identifying the location of ligand-binding pockets in proteins. (2006) applied an SVM method to predict DNA-binding sites using the features including amino acid sequence, profile of evolutionary conservation of sequence positions, and low-resolution structural information. (2006) developed a method to predict both protein-protein binding site location and interface type (obligate or non-obligate) using a Bayesian network in combination with surface patch analysis. cache = ./cache/cord-346965-0oq2n0af.txt txt = ./txt/cord-346965-0oq2n0af.txt === reduce.pl bib === id = cord-352481-iq3wor3w author = Postic, Guillaume title = An information gain-based approach for evaluating protein structure models date = 2020-08-18 pages = extension = .txt mime = text/plain words = 6518 sentences = 328 flesch = 52 summary = Although these statistical potentials are not to be confused with their physics-based counterparts of the same name—i.e. PMFs obtained by molecular dynamics simulations—their particular success in assessing the native-like character of protein structure predictions has lead authors to consider the computed scores as approximations of the free energy. In this article, we present a conceptually new method for ranking protein structure models by quality, which is (i) independent of any physics-based explanation and (ii) relevant to statistics and to a general definition of information gain. As a proof of concept, we have built two scoring functions, respectively based on the new and the PMF equations, and compared their performance at ranking predicted structures of proteins by their quality. Using the reference dataset 3DRobot (n=60,200 structures) [35] , we show that the scoring function built with our new formalism is more accurate than statistical PMFs, based on three types of performance evaluation. cache = ./cache/cord-352481-iq3wor3w.txt txt = ./txt/cord-352481-iq3wor3w.txt === reduce.pl bib === id = cord-356064-q56jnhss author = Bartel, Sebastian title = Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides date = 2011-08-01 pages = extension = .txt mime = text/plain words = 6164 sentences = 314 flesch = 45 summary = title: Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides In this report the proteome of HEK293 cells infected with Vaccinia Virus strain IHD-W was analyzed by 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS in a bottom-up approach. Derivatization of peptides with 4-sulfophenyl isothiocyanate (SPITC) carried out on ZipTipμ-C18 columns enabled protein identification via the peptides' primary sequence, providing improved s/n ratios as well as signal intensities of the PSD spectra. The E3L gene product has been identified in HEK 293 cells infected with active VACV IHD-W, which is in correlation to proteome analysis of VACV virions that indicate that the putative double-stranded RNA binding protein (D-1) is not present in the virion but is expressed in the early replication phase. Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides cache = ./cache/cord-356064-q56jnhss.txt txt = ./txt/cord-356064-q56jnhss.txt === reduce.pl bib === id = cord-346916-jj4l9ydl author = Girardi, Erika title = Roadblocks and fast tracks: How RNA binding proteins affect the viral RNA journey in the cell date = 2020-08-23 pages = extension = .txt mime = text/plain words = 13119 sentences = 728 flesch = 45 summary = Moreover, despite the molecular mimicry set by RNA viruses to resemble cellular mRNAs and escape host recognition, the viral nucleic acid still needs to embark on a long journey through a hostile cell environment and must overcome the obstacles put in place by the host antiviral system in order to be translated and replicated. Another example, is the zinc-finger antiviral protein (ZAP), which binds vRNAs containing a ZAP response element (ZRE) and induces RNA degradation via interaction of its N-terminal domain with host decay machinery mediated [75] (Fig. 1 ). In fact, IRES elements present in the genome of different families of RNA viruses lack overall conserved features [146, 147] .The classification of viral IRESs in four types stems from their structural organization, their respective dependence on sets of translation initiation factors, and whether they use scanning or instead directly recruit ribosomes to the start codon [148] (Fig. 2) . cache = ./cache/cord-346916-jj4l9ydl.txt txt = ./txt/cord-346916-jj4l9ydl.txt === reduce.pl bib === id = cord-355924-8sk9al0n author = Allam, Loubna title = Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules date = 2020-10-21 pages = extension = .txt mime = text/plain words = 4753 sentences = 288 flesch = 52 summary = Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. For this purpose, a targeted analysis of the expression of candidate genes involved in SARS-CoV-2 infection confirmed the presence of the GRP78 protein in vitro in epithelial cells of the human respiratory tract and lung tissue. In this direction, our study focused on the repositioning of approved drugs as well as the investigation of other bioactive compounds that may prevent the penetration of SARS-CoV-2 into host cells by targeting the region of GRP78 that is required for the interaction with the Spike protein of the virus. Inhibition of the interaction between the spike protein SARS-CoV-2 and the receptor by blocking the GRP78 is a strategy interesting to identify drugs that decrease the rate of viral infection. cache = ./cache/cord-355924-8sk9al0n.txt txt = ./txt/cord-355924-8sk9al0n.txt === reduce.pl bib === id = cord-348972-r94fhpe0 author = Gussow, Ayal B. title = Machine-learning approach expands the repertoire of anti-CRISPR protein families date = 2020-07-29 pages = extension = .txt mime = text/plain words = 9653 sentences = 505 flesch = 54 summary = The most striking and obvious common feature of the Acrs is their small size (weighted mean Acr length: 104 aa, Table 1 ), and the tendency to form sets of small proteins that are encoded by co-directional and closely spaced genes in (pro)virus genomes (hereafter directons; Fig. 1 , Table 1 ). As genes encoding Acrs tend to form small directons, we sought to estimate a heuristic maximum threshold for the mean directon size in a candidate family that would enrich our protein set for true Acrs. The initial set consisted of 232,616 clusters and was first filtered for clusters that included at least one member with an HTH-domain-containing protein encoded downstream, and at least one member from a self-targeting genome, two hallmark Acr characteristics 20 . cache = ./cache/cord-348972-r94fhpe0.txt txt = ./txt/cord-348972-r94fhpe0.txt === reduce.pl bib === id = cord-351559-az4pgi9k author = Turjya, Rafeed Rahman title = Perversely expressed long noncoding RNAs can alter host response and viral proliferation in SARS-CoV-2 infection date = 2020-06-29 pages = extension = .txt mime = text/plain words = 2438 sentences = 173 flesch = 48 summary = Regulatory roles of long non-coding RNAs (lncRNAs) during viral infection and associated antagonism of host antiviral immune responses has become more evident in last decade. To elucidate possible functions of lncRNAs in the COVID-19 pathobiology, we have utilized RNA-seq dataset of SARS-CoV-2 infected lung epithelial cells. By network enrichment analysis we find that these lncRNAs can directly interact with differentially expressed protein-coding genes ADAR, EDN1, KYNU, MALL, TLR2 and YWHAG; and also AKAP8L, EXOSC5, GDF15, HECTD1, LARP4B, LARP7, MIPOL1, UPF1, MOV10 and PRKAR2A, host genes that interact with SARS-CoV-2 proteins. Conclusions Our investigation determines that deregulated lncRNAs in SARS-CoV-2 infection are involved in viral proliferation, cellular survival, and immune response, ultimately determining disease outcome and this information could drive the search for novel RNA therapeutics as a treatment option. cache = ./cache/cord-351559-az4pgi9k.txt txt = ./txt/cord-351559-az4pgi9k.txt === reduce.pl bib === id = cord-355377-b0rcg3rt author = van der Vlag, R. title = Analytical Methods in Protein-Templated Dynamic Combinatorial Chemistry date = 2017-06-29 pages = extension = .txt mime = text/plain words = 9842 sentences = 518 flesch = 53 summary = Protein-templated dynamic combinatorial chemistry (DCC) has emerged as a powerful method to identify new inhibitors given that it enables the protein to select its own best binder(s) from a library of interconverting compounds. Both DCLs showed a very clear amplification of acylhydrazones: t-butylphenyl and thiophenyl acylhydrazones 4-5c and 4-5g were amplified in presence of hGST P1-1 and SjGST, Scheme 3 Generation of acylhydrazone-based dynamic combinatorial libraries of (A) aldehydes 4 or 6 and hydrazides 5a-j. The protein concentration can be very low, but 1 H-waterLOGSY 21 can be limited by the exchange kinetics of the reversibly formed protein-ligand complexes and might still suffer from overlapping signals, especially for large DCLs. In 2013, the same group introduced a competition-based 1 H-NMR method to screen binders for human 2-oxoglutarate (2OG)dependent oxygenases. cache = ./cache/cord-355377-b0rcg3rt.txt txt = ./txt/cord-355377-b0rcg3rt.txt === reduce.pl bib === id = cord-354547-eomm1sl5 author = Wang, Jibin title = Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding date = 2009-03-16 pages = extension = .txt mime = text/plain words = 6319 sentences = 295 flesch = 51 summary = title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding In this study, we report that interaction between coronavirus membrane protein (M) and actin with functional implication in facilitating virion assembly and budding. Similarly, analysis of cells expressing the M protein either on its own or together with the Myc-tagged actin by Western blot with anti-M polyclonal antibodies showed the detection of the full-length glycosylated (two upper bands) and unglycosylated (25 kDa) forms of the M protein (Fig. 2, lanes 5 and 6) . In cells transfected with both wild type and MD5 constructs with or without IBV infection, detection of similar amounts of M protein was observed (Fig. 5b, top two panels, lanes 1 and 2) , suggesting that both constructs were expressed at similar efficiencies. cache = ./cache/cord-354547-eomm1sl5.txt txt = ./txt/cord-354547-eomm1sl5.txt === reduce.pl bib === id = cord-354950-kmpbdvof author = Demurtas, Olivia C. title = Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS date = 2016-02-05 pages = extension = .txt mime = text/plain words = 8651 sentences = 406 flesch = 51 summary = Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. In addition, the WHO guidelines for SARS diagnosis, developed during the outbreak in 2003, suggested the use of N-based ELISA for specific IgG detection as confirmatory test of SARS-CoV infection (World Health Organization [WHO] , 2003 SARS: Laboratory diagnostic tests) due to the ability of the host to mount an early antibody response against the N protein (Che et al., 2004) . As the plant-derived recombinant M protein, the M RLV was also specifically recognized by the mouse anti-M pAb ( Figure 6C ) that had previously validated by Immunofluorescence Antibody Assay (IFA) in SARS CoV infected Vero cells (Carattoli et al., 2005) . cache = ./cache/cord-354950-kmpbdvof.txt txt = ./txt/cord-354950-kmpbdvof.txt === reduce.pl bib === id = cord-347710-ff64y6ef author = Wan, Qianya title = Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date = 2020-07-13 pages = extension = .txt mime = text/plain words = 36567 sentences = 2487 flesch = 46 summary = hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. 6, 13 It is well known that Hsp90 not only interacts and contributes to RNA polymerase assembly and nuclear import of some (−) ssRNA viruses (e.g., PB2 of influenza virus), but plays crucial roles in the folding process of viral capsid proteins and virion assemblies as well. 17, 18 As a critical component of cellular protein surveillance, the ATP-dependent molecular chaperone protects cells from damage caused by stress and takes part in a number of folding processes, including folding of newly synthesized polypeptides, recognition and refolding of misfolded or aggregated proteins, solubilization or degradation of proteins, transporting proteins, assembly or disassembly of oligomeric protein complexes, and the regulation of certain natively folded proteins. cache = ./cache/cord-347710-ff64y6ef.txt txt = ./txt/cord-347710-ff64y6ef.txt ===== Reducing email addresses cord-013046-r6dtiu97 cord-004584-bcw90f5b cord-004400-li1sc47z cord-014597-66vd2mdu cord-001835-0s7ok4uw cord-004534-jqm1hxps cord-034191-qqb2knmo cord-196265-mvnkkcow cord-022955-vy0qgtll cord-008777-i2reanan 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cord-354547-eomm1sl5 cord-334511-lx9608vy cord-348972-r94fhpe0 cord-354950-kmpbdvof cord-346965-0oq2n0af cord-346916-jj4l9ydl cord-355377-b0rcg3rt cord-342756-rgm9ffpk cord-347710-ff64y6ef cord-031907-ilhr3iu5 cord-022940-atbjwpo5 Creating transaction Updating pos table Building ./etc/reader.txt cord-022940-atbjwpo5 cord-347710-ff64y6ef cord-001835-0s7ok4uw cord-023209-un2ysc2v cord-004948-ad3i9wgj cord-023208-w99gc5nx number of items: 541 sum of words: 5,751,766 average size in words: 13,013 average readability score: 46 nouns: protein; proteins; cells; cell; virus; expression; membrane; activity; analysis; structure; gene; results; sequence; study; infection; acid; role; host; receptor; data; studies; peptide; domain; system; type; disease; dna; interaction; peptides; patients; interactions; viruses; response; function; surface; amino; residues; production; levels; replication; model; coronavirus; mice; methods; effect; effects; activation; formation; development; fusion verbs: using; showed; binding; based; induced; find; containing; identified; include; increases; suggesting; associated; involved; expressing; compared; requires; provided; determined; mediated; indicated; known; follows; developed; revealed; observed; lead; produced; form; regulating; result; performing; obtained; demonstrated; reduced; targeted; inhibited; cause; investigating; study; detected; reported; derived; predict; described; allow; interact; encoding; activating; generated; related adjectives: viral; human; different; specific; high; molecular; structural; cellular; new; important; several; immune; non; functional; small; many; dependent; novel; similar; like; single; anti; low; large; potential; present; recombinant; first; various; higher; significant; biological; major; active; multiple; possible; clinical; nuclear; respiratory; complex; free; positive; acute; essential; severe; therapeutic; bacterial; key; experimental; intracellular adverbs: also; however; well; therefore; highly; respectively; significantly; recently; previously; furthermore; even; moreover; still; directly; together; often; currently; interestingly; specifically; first; finally; now; mainly; especially; yet; rather; less; particularly; far; subsequently; usually; thereby; much; strongly; approximately; relatively; potentially; generally; indeed; widely; additionally; already; similarly; hence; fully; probably; successfully; almost; completely; clearly pronouns: we; it; their; its; our; they; i; them; us; his; itself; one; he; themselves; you; your; her; my; she; mrnas; me; nsp10; ourselves; nsp15; ifitm3; him; s; ashcs; p~; imagej; e3s; c328; s230; rss1gfp; mine; u; mg; iga+; grasp55; egfp; yourself; wtgfp; svlps; rab8; orf16; oneself; isg15-/-bmdm; interleukin-15; igg4; iga1 proper nouns: SARS; RNA; C; CoV-2; Fig; S; M; CoV; T; N; MS; ER; Golgi; II; B; University; A; Protein; HIV-1; IFN; mRNA; PCR; E.; ACE2; K; S.; DNA; pH; NMR; Table; HIV; mg; D; COVID-19; MHC; L; F; ELISA; C.; M.; HCV; ATP; Coronavirus; S1; CD4; G; Institute; PEDV; SP; I keywords: protein; sars; cell; rna; virus; dna; structure; sequence; golgi; gene; vaccine; study; peptide; membrane; expression; human; ace2; university; covid-19; cov-2; viral; result; plant; acid; pcr; interaction; hiv-1; activity; drug; mhc; nmr; high; epitope; receptor; institute; ifn; atp; antibody; increase; hcv; pedv; patient; method; lipid; ibv; host; elisa; effect; disease; autophagy one topic; one dimension: protein file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667425/ titles(s): Multiplexed Nucleic Acid Programmable Protein Arrays three topics; one dimension: protein; protein; cells file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134330/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131717/, https://api.elsevier.com/content/article/pii/S0065277606920069 titles(s): ECB12: 12th European Congess on Biotechnology | Regulation of Protein Synthesis in Virus-Infected Animal Cells | Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions five topics; three dimensions: protein proteins using; protein virus proteins; cells cell protein; cells cell protein; patients protein serum file(s): https://doi.org/10.3390/molecules25204597, https://www.sciencedirect.com/science/article/pii/S0065352705640067, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941590/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102153/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103196/ titles(s): NMR as a “Gold Standard” Method in Drug Design and Discovery | Molecular Interactions in the Assembly of Coronaviruses | Critical physiological and pathological functions of Forkhead Box O tumor suppressors | Übersicht Über neue ernährungswissenschaftliche Publikationen | 40th Annual Meeting of the GTH (Gesellschaft für Thrombose- und Hämostaseforschung) Type: cord title: keyword-protein-cord date: 2021-05-25 time: 16:08 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:protein ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-302514-rstvf3mc author: Abbas, Wasim title: The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections date: 2015-04-07 words: 5138.0 sentences: 283.0 pages: flesch: 38.0 cache: ./cache/cord-302514-rstvf3mc.txt txt: ./txt/cord-302514-rstvf3mc.txt summary: Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer, and lung cancer. Overexpression of eEF1A2 protein up-regulates overall PI4K activity and cellular phosphatidylinositol 4-phosphate (PI4P) generation in human cells. In addition, high-resolution analysis of genomic aberration by metaphase and comparative genomic hybridization array identify the involvement of the 20q region, suggesting the potential role of eEF1A2 as a candidate tumor gene in lung cancer cell lines (41) . eEF1A2 interacts directly with Prx-1 and protects the cells from stress-induced apoptosis by the down-regulation of caspase-3 and caspase-8 activation parallel to increased expression of the pro-survival factor Akt (76, 77) . Elongation factor 1 alpha interacts with phospho-Akt in breast cancer cells and regulates their proliferation, survival and motility Expression profile of eukaryotic translation factors in human cancer tissues and cell lines abstract: Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer, and lung cancer. eEF1A1 modulates cytoskeleton, exhibits chaperone-like activity and also controls cell proliferation and cell death. In contrast, eEF1A2 protein favors oncogenesis as shown by the fact that overexpression of eEF1A2 leads to cellular transformation and gives rise to tumors in nude mice. The eEF1A2 protein stimulates the phospholipid signaling and activates the Akt-dependent cell migration and actin remodeling that ultimately favors tumorigenesis. In contrast, inactivation of eEF1A proteins leads to immunodeficiency, neural and muscular defects, and favors apoptosis. Finally, eEF1A proteins interact with several viral proteins resulting in enhanced viral replication, decreased apoptosis, and increased cellular transformation. This review summarizes the recent findings on eEF1A proteins indicating that eEF1A proteins play a critical role in numerous human diseases through enhancement of oncogenesis, blockade of apoptosis, and increased viral pathogenesis. url: https://doi.org/10.3389/fonc.2015.00075 doi: 10.3389/fonc.2015.00075 id: cord-274056-9t3kneoo author: Abd Elwahaab, Marwa A. title: A Statistical Similarity/Dissimilarity Analysis of Protein Sequences Based on a Novel Group Representative Vector date: 2019-05-08 words: 3314.0 sentences: 251.0 pages: flesch: 59.0 cache: ./cache/cord-274056-9t3kneoo.txt txt: ./txt/cord-274056-9t3kneoo.txt summary: title: A Statistical Similarity/Dissimilarity Analysis of Protein Sequences Based on a Novel Group Representative Vector For beta globin protein sequences, seven species are selected in our sample set: human, chimpanzee, gorilla, mouse, rat, gallus, and opossum, as illustrated in Table 1 . The similarity/dissimilarity vectors that are corresponding to beta globin, ND5, and spike protein sequences are illustrated in Tables 9, 10, and 11, respectively, based on the two methods discussed before. The results in Table 10 show that both the magnitude ( 5 ) and the angle ( 5 ) can measure similarity/dissimilarity degree well among ND5 protein sequences as shown in Figure 2 . The similarity/dissimilarity analysis among the seven beta globin sequences measured according to ( 5 ) is illustrated in Table 12 and shown in Figure 4 . The similarity/dissimilarity analysis among the beta globin sequences measured according to (GR spike ) is illustrated in Table 14 and shown in Figure 6 . abstract: Similarity/dissimilarity analysis is a key way of understanding the biology of an organism by knowing the origin of the new genes/sequences. Sequence data are grouped in terms of biological relationships. The number of sequences related to any group is susceptible to be increased every day. All the present alignment-free methods approve the utility of their approaches by producing a similarity/dissimilarity matrix. Although this matrix is clear, it measures the degree of similarity among sequences individually. In our work, a representative of each of three groups of protein sequences is introduced. A similarity/dissimilarity vector is evaluated instead of the ordinary similarity/dissimilarity matrix based on the group representative. The approach is applied on three selected groups of protein sequences: beta globin, NADH dehydrogenase subunit 5 (ND5), and spike protein sequences. A cross-grouping comparison is produced to ensure the singularity of each group. A qualitative comparison between our approach, previous articles, and the phylogenetic tree of these protein sequences proved the utility of our approach. url: https://doi.org/10.1155/2019/8702968 doi: 10.1155/2019/8702968 id: cord-347714-vxxhglx7 author: Abitogun, Folagbade title: COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding date: 2020-10-14 words: 3707.0 sentences: 191.0 pages: flesch: 44.0 cache: ./cache/cord-347714-vxxhglx7.txt txt: ./txt/cord-347714-vxxhglx7.txt summary: (10, 11) The structure of the spike glycoprotein of the virus is also an extended similarity with SARS-CoV, (4) which together with COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding other proteins of the virus are candidates for vaccine development and are being explored in different settings due to the active roles of the proteins in the infectivity of the virus. (18) However studies have shown that full length spike protein vaccines for SARS-CoV may lead to antibody mediated disease enhancement causing inflammatory and liver damage in animal models (19, 20) which is why in this manuscript, we applied immuno-informatics "in silico" approaches to identify potential CD8+ cytotoxic T Cell epitopes from proteins of SARS-CoV-2, SARS-CoV and MERS-CoV. Multi-epitope Based Peptide Vaccine Design Using Three Structural Proteins (S, E, and M) of SARS-CoV-2: An In Silico Approach abstract: The COVID19 pandemic has resulted in 1,092,342 deaths as of 14th October 2020, indicating the urgent need for a vaccine. This study highlights novel protein sequences generated by shot gun sequencing protocols that could serve as potential antigens in the development of novel subunit vaccines and through a stringent inclusion criterion, we characterized these protein sequences and predicted their 3D structures. We found distinctly antigenic sequences from the SARS-CoV-2 that have led to identification of 4 proteins that demonstrate an advantageous binding with Human leukocyte antigen-1 molecules. Results show how previously unexplored proteins may serve as better candidates for subunit vaccine development due to their high stability and immunogenicity, reinforce by their HLA-1 binding propensities and low global binding energies. This study thus takes a unique approach towards furthering the development of vaccines by employing multiple consensus strategies involved in immuno-informatics technique. url: https://doi.org/10.1101/2020.10.14.339689 doi: 10.1101/2020.10.14.339689 id: cord-327934-hjimlb6i author: Acar, Delphine D. title: Identification of peptide domains involved in the subcellular localization of the feline coronavirus 3b protein date: 2019-10-01 words: 6784.0 sentences: 352.0 pages: flesch: 44.0 cache: ./cache/cord-327934-hjimlb6i.txt txt: ./txt/cord-327934-hjimlb6i.txt summary: Transfection of different cell types with FCoV 3b fused to enhanced green fluorescent protein (EGFP) or 3×FLAG confirmed localization of FCoV 3b in the mitochondria and nucleoli. Transport of larger proteins to the nucleus, however, is an ATP-dependent active process driven by nuclear localization signals (NLSs), which are typically characterized by clusters of basic amino acids (reviewed in [38] [39] [40] [41] [42] ). The nucleocapsid proteins of several members of the order Nidovirales, such as porcine reproductive and respiratory syndrome virus (PRRSV, family Arteriviridae) [70, [77] [78] [79] [80] , transmissible gastroenteritis virus (TGEV) [81] , mouse hepatitis virus (MHV) [81, 82] and infectious bronchitis virus (IBV) [82] [83] [84] [85] (family Coronaviridae), also target the nucleolus and have been shown to incorporate one or more potential NLSs. Similarly, the SARS-CoV 3b protein was predicted to have two overlapping NLSs, a pat4 and bipartite motif, that were shown to be associated with nuclear (nucleolar) localization [27] . abstract: Feline coronavirus (FCoV) has been identified as the aetiological agent of feline infectious peritonitis (FIP), a highly fatal systemic disease in cats. FCoV open reading frame 3 (ORF3) encodes accessory proteins 3a, 3b and 3 c. The FCoV 3b accessory protein consists of 72 amino acid residues and localizes to nucleoli and mitochondria. The present work focused on peptide domains within FCoV 3b that drive its intracellular trafficking. Transfection of different cell types with FCoV 3b fused to enhanced green fluorescent protein (EGFP) or 3×FLAG confirmed localization of FCoV 3b in the mitochondria and nucleoli. Using serial truncated mutants, we showed that nucleolar accumulation is controlled by a joint nucleolar and nuclear localization signal (NoLS/NLS) in which the identified overlapping pat4 motifs (residues 53–57) play a critical role. Mutational analysis also revealed that mitochondrial translocation is mediated by N-terminal residues 10–35, in which a Tom20 recognition motif (residues 13–17) and two other overlapping hexamers (residues 24–30) associated with mitochondrial targeting were identified. In addition, a second Tom20 recognition motif was identified further downstream (residues 61–65), although the mitochondrial translocation evoked by these residues seemed less efficient as a diffuse cytoplasmic distribution was also observed. Assessing the spatiotemporal distribution of FCoV 3b did not provide convincing evidence of dynamic shuttling behaviour between the nucleoli and the mitochondria. url: https://www.ncbi.nlm.nih.gov/pubmed/31483243/ doi: 10.1099/jgv.0.001321 id: cord-341701-zropd3mo author: Adhikari, Subash title: A high-stringency blueprint of the human proteome date: 2020-10-16 words: 10138.0 sentences: 533.0 pages: flesch: 33.0 cache: ./cache/cord-341701-zropd3mo.txt txt: ./txt/cord-341701-zropd3mo.txt summary: During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. • Be a focal point for life sciences researchers, pathologists, clinicians and industry communities seeking to translate and leverage proteomic and proteogenomic data to improve human health through: (i) greater understanding of the molecular mechanisms of common and rare diseases, (ii) identification of pathophysiological changes to generate disease and wellness diagnostic biomarkers, and (iii) development of new effective and safe personalized therapeutics. The HPP Ab Resource Pillar, ostensibly led by the Human Protein Atlas (HPA; www.proteinatlas.org), was initiated in 2003 and uses Ab-based strategies to analyse spatio-temporal aspects of the proteome 39 . Community encouragement to identify biological data that complement high-stringency MS strategies to accelerate discovery and understanding of human proteome PE2,3,4 missing proteins. abstract: The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases. url: https://doi.org/10.1038/s41467-020-19045-9 doi: 10.1038/s41467-020-19045-9 id: cord-325230-3kg4oe4g author: Agol, Vadim I. title: Viral security proteins: counteracting host defences date: 2010-11-09 words: 8716.0 sentences: 426.0 pages: flesch: 41.0 cache: ./cache/cord-325230-3kg4oe4g.txt txt: ./txt/cord-325230-3kg4oe4g.txt summary: These proteins include: capsid proteins; an RNA-dependent RNA polymerase (3D pol ); a protein (VPg, or 3B) that serves as a primer for the initiation of RNA synthesis; an ATPase with a conserved superfamily 3 helicase motif (2C ATPase ) and an essential but poorly defined role in viral RNA replication; a chymotrypsin-like protease (3C pro ), which, as the mature protein or as a precursor, is a major factor in polyprotein processing; two hydrophobic membrane-binding proteins (2B and 3A) that participate in the generation of a virus-friendly environment; and, flanking the precursor of the capsid proteins, one or two highly variable proteins (L and 2A), the structure and functions of which are the subject of this Review. abstract: Interactions with host defences are key aspects of viral infection. Various viral proteins perform counter-defensive functions, but a distinct class, called security proteins, is dedicated specifically to counteracting host defences. Here, the properties of the picornavirus security proteins L and 2A are discussed. These proteins have well-defined positions in the viral polyprotein, flanking the capsid precursor, but they are structurally and biochemically unrelated. Here, we consider the impact of these two proteins, as well as that of a third security protein, L(*), on viral reproduction, pathogenicity and evolution. The concept of security proteins could serve as a paradigm for the dedicated counter-defensive proteins of other viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro2452) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1038/nrmicro2452 doi: 10.1038/nrmicro2452 id: cord-333089-ufyzqgqk author: Aguilar-Pineda, Jorge Alberto title: Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry date: 2020-07-29 words: 6957.0 sentences: 359.0 pages: flesch: 51.0 cache: ./cache/cord-333089-ufyzqgqk.txt txt: ./txt/cord-333089-ufyzqgqk.txt summary: Based on the structural complementarity and steric impediments between the S protein and human ACE2 (hACE2) protein membranes, we mapped the glycosylation sites of both models [21] [22] [23] [24] and performed molecular dynamics simulations (MDS) by 250 ns to stabilize the glycosylated SARS-CoV2 spike (S) and hACE2 complex (suppl. Given the possibility that occupancy at glycosylated residues or S-RBD binding sites by estrogens could modify the affinity of the SARS-CoV2 virus and alter entry into the cell thereby reducing infectivity, we sought to further examine these interactions using a range of complementary experimental approaches (see Table S1 ). In an effort to explore the potential protective effects of female sex hormones against SARS-CoV-2 infection, we examined the impact of estradiol (17β-diol) and a dietary-derived phytoestrogen (S-equol) on hACE2 structure and protein expression by a combination of in silico modeling, in vitro, and in vivo analysis. abstract: Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further observed that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV2 thereby blocking its entry into cells. In a mouse model, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19. url: https://doi.org/10.1101/2020.07.29.227249 doi: 10.1101/2020.07.29.227249 id: cord-258624-041cf99j author: Ahmad, Sajjad title: Design of a Novel Multi Epitope-Based Vaccine for Pandemic Coronavirus Disease (COVID-19) by Vaccinomics and Probable Prevention Strategy against Avenging Zoonotics date: 2020-05-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The emergence and rapid expansion of the coronavirus disease (COVID-19) require the development of effective countermeasures especially a vaccine to provide active acquired immunity against the virus. This study presented a comprehensive vaccinomics approach applied to the complete protein data published so far in the National Center for Biotechnological Information (NCBI) coronavirus data hub. We identified non-structural protein 8 (Nsp8), 3C-like proteinase, and spike glycoprotein as potential targets for immune responses to COVID-19. Epitopes prediction illustrated both B-cell and T-cell epitopes associated with the mentioned proteins. The shared B and T-cell epitopes: DRDAAMQRK and QARSEDKRA of Nsp8, EDMLNPNYEDL and EFTPFDVVR of 3C-like proteinase, and VNNSYECDIPI of the spike glycoprotein are regions of high potential interest and have a high likelihood of being recognized by the human immune system. The vaccine construct of the epitopes shows stimulation of robust primary immune responses and high level of interferon gamma. Also, the construct has the best conformation with respect to the tested innate immune receptors involving vigorous molecular mechanics and solvation energy. Designing of vaccination strategies that target immune response focusing on these conserved epitopes could generate immunity that not only provide cross protection across Betacoronaviruses but additionally resistant to virus evolution. url: https://doi.org/10.1016/j.ejps.2020.105387 doi: 10.1016/j.ejps.2020.105387 id: cord-103528-3tib5o1m author: Ahmed, Asad title: DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity date: 2020-09-28 words: 3798.0 sentences: 242.0 pages: flesch: 54.0 cache: ./cache/cord-103528-3tib5o1m.txt txt: ./txt/cord-103528-3tib5o1m.txt summary: title: DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity Here, we have incorporated Convolutional Neural Networks that find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies towards a diverse set of ligands. Initial raw data database created contained protein structures in PDB format, protein sequences in FASTA format, ligand in SDF format and binding affinity values of corresponding protein-ligand pairs for 5464 complexes. We propose a deep-learning based approach to predict ligand (eg., drug)-target binding affinity using only structures of target protein (PDB format) and ligand (SDF format) as inputs. We have trained two models to predict the binding affinity between protein and ligand in a given complex. We have constructed a novel dataset that represents a diverse set of ligands and using a novel deep learning based approach we have achieved significant improvement in prediction of binding affinity of protein-ligand complexes. abstract: Protein-ligand binding prediction has extensive biological significance. Binding affinity helps in understanding the degree of protein-ligand interactions and has wide protein applications. Protein-ligand docking using virtual screening and molecular dynamic simulations are required to predict the binding affinity of a ligand to its cognate receptor. In order to perform such analyses, it requires intense computational power and it becomes impossible to cover the entire chemical space of small molecules. It has been aided by a shift towards using Machine Learning-based methodologies that aids in binding prediction using regression. Recent developments using deep learning has enabled us to make sense of massive amounts of complex datasets. Herein, the ability of the model to “learn” intrinsic patterns in a complex plane of data is the strength of the approach. Here, we have incorporated Convolutional Neural Networks that find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies towards a diverse set of ligands. The models were trained and validated using a detailed methodology for feature extraction. We have also tested DEELIG on protein complexes relevant to the current public health scenario. Our approach to network construction and training on protein-ligand dataset prepared in-house has provided significantly better results than previously existing methods in the field. url: https://doi.org/10.1101/2020.09.28.316224 doi: 10.1101/2020.09.28.316224 id: cord-290445-vb53bih9 author: Ahmed, Shiek SSJ title: Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery date: 2020-04-23 words: 3793.0 sentences: 208.0 pages: flesch: 42.0 cache: ./cache/cord-290445-vb53bih9.txt txt: ./txt/cord-290445-vb53bih9.txt summary: Secondly, the viral replication machinery network from SET-B with 332 seed proteins extended to 1486 neighboring proteins with 11438 interacting edges which representing the mechanism attributed to evasion of the SARS-CoV2 genome into the host. Similarly, the viral replication machinery network was acquired with 1522 proteins with 9747 interacting edges showing the complex SARS-CoV-2 mechanism in the human lungs. These common molecules represent the inter-connecting mechanism involved in the transcription machinery, immune response, cell growth and/or maintenance, transport, metabolism, protein metabolism, cell communication and signal transduction that activated upon virus binding and has been subsequently utilized for viral replication process (S5 Table) Also mapping with other viral infection dataset, 50 hub proteins of the replication machinery network have noticed in influenza virus infection (S4 Table) , which suggests SARS-CoV2 and influenza may have a similar mode of host infection machinery [17] . The molecular pathways of interconnecting protein hubs could be the intermediate phase that connects the receptor activation mechanism and viral replication process (Fig 10) . abstract: We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. We constructed two independent lung protein interactome to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from both interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins of viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five interconnecting cascades between hubs of both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2. url: https://doi.org/10.1101/2020.04.20.050138 doi: 10.1101/2020.04.20.050138 id: cord-016442-3su3x6ed author: Aiking, Harry title: Transition Feasibility and Implications for Stakeholders date: 2006 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120718/ doi: 10.1007/1-4020-4842-4_7 id: cord-338485-4zqeq1se author: Aiking, Harry title: The next protein transition() date: 2018-07-27 words: 6836.0 sentences: 344.0 pages: flesch: 49.0 cache: ./cache/cord-338485-4zqeq1se.txt txt: ./txt/cord-338485-4zqeq1se.txt summary: With respect to sustainability, this is none too early, for there is a growing consensus that animal protein has disproportionate environmental impacts, particularly when produced in intensive production systems employing massive use of feed crops (Aiking, 2014; McMichael, Powles, Butler, & Uauy, 2007; Smil, 2001; Steinfeld et al., 2006; Westhoek et al., 2011) . Animal protein products such as meat and dairy are important to them from an economic perspective, but when employing intensive production systems these are wasteful of plant protein from an environmental point of view and inherently, therefore, wasteful of the resources required to grow feed crops, such as land, water, phosphate and fuel. Increase awareness of the impacts of animal-based protein on the environment, the urgency of this issue and the availability of solutions, but take into account that science-based health and sustainability arguments in favour of a diet change do not sufficiently reach consumers or are too difficult for them to comprehend (de Boer & Aiking, 2017) . abstract: BACKGROUND: Meeting the UN Sustainable Development Goals requires a relatively rapid transition towards a circular economy. Therefore, a multidisciplinary perspective is required to sketch why a transition from diets based primarily on animal proteins towards diets based primarily on plant proteins products is extremely urgent for both food security and sustainability. SCOPE AND APPROACH: This review starts out by identifying ecological, economic and social aspects of sustainable food consumption. Subsequently, it is argued how protein supply is underlying and linking the top-3 of anthropogenic impacts based on the planetary boundaries concept, i.e. 1) biodiversity loss, 2) nitrogen cycle acceleration, and 3) carbon cycle acceleration (resulting in climate change). These environmental impacts associated with current Western food consumption need to be reduced urgently. In order to address the inefficiencies inherent to current dietary patterns, therefore, a ranked list of more sustainable options is proposed, based on their order of magnitude. Addressing consumers, industry, and governmental stakeholders plus cultural aspects, challenges and options are sketched. KEY FINDINGS AND CONCLUSIONS: Clearly, a dietary transition from primarily animal towards plant protein products is required. Fortunately, new dietary guidelines are increasingly taking sustainability into account and the contours of a diet transition are slowly emerging. url: https://www.sciencedirect.com/science/article/pii/S0924224418301213 doi: 10.1016/j.tifs.2018.07.008 id: cord-319563-9lwr6k8p author: Aitekenov, Sultan title: Review: Detection and quantification of proteins in human urine date: 2020-10-14 words: 10099.0 sentences: 611.0 pages: flesch: 40.0 cache: ./cache/cord-319563-9lwr6k8p.txt txt: ./txt/cord-319563-9lwr6k8p.txt summary: This review focuses on the instrumental quantification (electrophoresis, chromatography, immunoassays, mass spectrometry, fluorescence spectroscopy, the infrared spectroscopy, and Raman spectroscopy) of proteins (the most of all albumin) in human urine matrix. Among the reasons that make urine challenging for researchers to analyze are: urine matrix is complex, it consists of various inorganic and organic compounds, from low-molar mass molecules to polymers; urine could contain cells, such as blood cells, or bacteria, which changes the composition of urine in time rapidly; an analytical method for diagnosis of proteinuria should cover protein presence in urine in a wide range from 0.01 mg/ml to 10 mg/ml. focuses on urinary proteins as potential biomarkers for mainly urine diseases, and capillary electrophoresis coupled mass spectroscopy as an instrumental method [33] . In this review, we focused on instrumental determination of abundant proteins in urine by electrophoresis, chromatography, mass spectrometry, immunoassay, fluorescence, IR, and Raman spectroscopy. abstract: Extensive medical research showed that patients, with high protein concentration in urine, have various kinds of kidney diseases, referred to as proteinuria. Urinary protein biomarkers are useful for diagnosis of many health conditions – kidney and cardio vascular diseases, cancers, diabetes, infections. This review focuses on the instrumental quantification (electrophoresis, chromatography, immunoassays, mass spectrometry, fluorescence spectroscopy, the infrared spectroscopy, and Raman spectroscopy) of proteins (the most of all albumin) in human urine matrix. Different techniques provide unique information on what constituents of the urine are. Due to complex nature of urine, a separation step by electrophoresis or chromatography are often used for proteomics study of urine. Mass spectrometry is a powerful tool for the discovery and the analysis of biomarkers in urine, however, costs of the analysis are high, especially for quantitative analysis. Immunoassays, which often come with fluorescence detection, are major qualitative and quantitative tools in clinical analysis. While Infrared and Raman spectroscopies do not give extensive information about urine, they could become important tools for the routine clinical diagnostics of kidney problems, due to rapidness and low-cost. Thus, it is important to review all the applicable techniques and methods related to urine analysis. In this review, a brief overview of each technique’s principle is introduced. Where applicable, research papers about protein determination in urine are summarized with the main figures of merits, such as the limit of detection, the detectable range, recovery and accuracy, when available. url: https://www.sciencedirect.com/science/article/pii/S0039914020310092?v=s5 doi: 10.1016/j.talanta.2020.121718 id: cord-034191-qqb2knmo author: Alayi, Tchilabalo D. title: Tandem Mass Tag-Based Serum Proteome Profiling for Biomarker Discovery in Young Duchenne Muscular Dystrophy Boys date: 2020-10-06 words: 8942.0 sentences: 439.0 pages: flesch: 48.0 cache: ./cache/cord-034191-qqb2knmo.txt txt: ./txt/cord-034191-qqb2knmo.txt summary: In this study, we sought to optimize and standardize a serum processing workflow in combination with tandem mass tag (TMT) multiplexing strategy to systematically survey the serum proteome of young untreated DMD boys and agematched healthy controls and identify biomarkers associated in the early stages of the disease. Serum samples from 4 year-old glucocorticoid naive DMD patients (n = 9) and age-matched healthy controls (n = 9) were processed for proteome profiling using our standardized multiplexing TMT-based mass spectrometry method described above. As expected, a large number of identified biomarkers (50%) that were found to be elevated in sera of these young DMD boys relative to the healthy controls were of muscle origin based on Gene Ontology molecular function annotations ( Figure S2 ) and information collected using Mass Spectrometry Data Analysis tools. abstract: [Image: see text] Blood-accessible molecular biomarkers are becoming highly attractive tools to assess disease progression and response to therapies in Duchenne muscular dystrophy (DMD) especially in very young patients for whom other outcome measures remain subjective and challenging. In this study, we have standardized a highly specific and reproducible multiplexing mass spectrometry method using the tandem mass tag (TMT) strategy in combination with depletion of abundant proteins from serum and high-pH reversed-phase peptide fractionation. Differential proteome profiling of 4 year-old DMD boys (n = 9) and age-matched healthy controls (n = 9) identified 38 elevated and 50 decreased serum proteins (adjusted P < 0.05, FDR <0.05) in the DMD group relative to the healthy control group. As expected, we confirmed previously reported biomarkers but also identified novel biomarkers. These included novel muscle injury-associated biomarkers such as telethonin, smoothelin-like protein 1, cofilin-1, and plectin, additional muscle-specific enzymes such as UTP–glucose-1-phosphate uridylyltransferase, aspartate aminotransferase, pyruvate kinase PKM, lactotransferrin, tissue alpha-l-fucosidase, pantetheinase, and ficolin-1, and some pro-inflammatory and cell adhesion-associated biomarkers such as leukosialin, macrophage receptor MARCO, vitronectin, galectin-3-binding protein, and ProSAAS. The workflow including serum depletion, sample processing, and mass spectrometry analysis was found to be reproducible and stable over time with CV < 20%. Furthermore, the method was found to be superior in terms of specificity compared to other multiplexing affinity-based methods. These findings demonstrate the specificity and reliability of TMT-based mass spectrometry methods in detection and identification of serum biomarkers in presymptomatic young DMD patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581259/ doi: 10.1021/acsomega.0c03206 id: cord-294125-v2dr4hm0 author: Albert, Manuel title: ISG15, a Small Molecule with Huge Implications: Regulation of Mitochondrial Homeostasis date: 2018-11-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viruses are responsible for the majority of infectious diseases, from the common cold to HIV/AIDS or hemorrhagic fevers, the latter with devastating effects on the human population. Accordingly, the development of efficient antiviral therapies is a major goal and a challenge for the scientific community, as we are still far from understanding the molecular mechanisms that operate after virus infection. Interferon-stimulated gene 15 (ISG15) plays an important antiviral role during viral infection. ISG15 catalyzes a ubiquitin-like post-translational modification termed ISGylation, involving the conjugation of ISG15 molecules to de novo synthesized viral or cellular proteins, which regulates their stability and function. Numerous biomedically relevant viruses are targets of ISG15, as well as proteins involved in antiviral immunity. Beyond their role as cellular powerhouses, mitochondria are multifunctional organelles that act as signaling hubs in antiviral responses. In this review, we give an overview of the biological consequences of ISGylation for virus infection and host defense. We also compare several published proteomic studies to identify and classify potential mitochondrial ISGylation targets. Finally, based on our recent observations, we discuss the essential functions of mitochondria in the antiviral response and examine the role of ISG15 in the regulation of mitochondrial processes, specifically OXPHOS and mitophagy. url: https://www.ncbi.nlm.nih.gov/pubmed/30428561/ doi: 10.3390/v10110629 id: cord-319780-rfj9t99r author: Alexander, S.P.H. title: A rational roadmap for SARS‐CoV‐2/COVID‐19 pharmacotherapeutic research and development. IUPHAR Review 29 date: 2020-05-01 words: 15196.0 sentences: 814.0 pages: flesch: 47.0 cache: ./cache/cord-319780-rfj9t99r.txt txt: ./txt/cord-319780-rfj9t99r.txt summary: Analysis of the co-crystal structure suggested that the SARS spike protein binds to the active site of angiotensin converting enzyme 2 (ACE2, Li et al., 2005) . A truncated version of human recombinant ACE2, lacking the transmembrane domain, mitigated against SARS-CoV infection of cells (Li et al., 2003) and has been used in animal models to reduce symptoms of severe acute lung failure , diabetic nephropathy (Oudit et al., 2010) and cardiac hypertrophy and fibrosis . A recent cryo-EM structure suggested that ACE2 and B 0 AT1/SLC6A19 form a heterodimer which pairs up through interfaces between the two ACE2 partners (Figure 1) , with the RBD of SARS-CoV-2 spike protein binding to the peptidase active site of ACE2 suggesting that B 0 AT1/SLC6A19 may facilitate entry of the novel coronavirus. Tumor necrosis factor- convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) abstract: In this review, we identify opportunities for drug discovery in the treatment of COVID‐19 and in so doing, provide a rational roadmap whereby pharmacology and pharmacologists can mitigate against the global pandemic. We assess the scope for targetting key host and viral targets in the mid‐term, by first screening these targets against drugs already licensed; an agenda for drug re‐purposing, which should allow rapid translation to clinical trials. A simultaneous, multi‐pronged approach using conventional drug discovery methodologies aimed at discovering novel chemical and biological means targetting a short‐list of host and viral entities should extend the arsenal of anti‐SARS‐CoV‐2 agents. This longer‐term strategy would provide a deeper pool of drug choices for future‐proofing against acquired drug resistance. Second, there will be further viral threats, which will inevitably evade existing vaccines. This will require a coherent therapeutic strategy which pharmacology and pharmacologists are best placed to provide. url: https://www.ncbi.nlm.nih.gov/pubmed/32358833/ doi: 10.1111/bph.15094 id: cord-355924-8sk9al0n author: Allam, Loubna title: Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules date: 2020-10-21 words: 4753.0 sentences: 288.0 pages: flesch: 52.0 cache: ./cache/cord-355924-8sk9al0n.txt txt: ./txt/cord-355924-8sk9al0n.txt summary: Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. For this purpose, a targeted analysis of the expression of candidate genes involved in SARS-CoV-2 infection confirmed the presence of the GRP78 protein in vitro in epithelial cells of the human respiratory tract and lung tissue. In this direction, our study focused on the repositioning of approved drugs as well as the investigation of other bioactive compounds that may prevent the penetration of SARS-CoV-2 into host cells by targeting the region of GRP78 that is required for the interaction with the Spike protein of the virus. Inhibition of the interaction between the spike protein SARS-CoV-2 and the receptor by blocking the GRP78 is a strategy interesting to identify drugs that decrease the rate of viral infection. abstract: The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies. To this end, we aimed to explore novel inhibitor compounds that can stop replication or decrease the viral load of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is currently no approved treatment. Besides using the angiotensin-converting enzyme (ACE2) receptor as a main gate, the CoV-2 can bind to the glucose-regulating protein 78 (GRP78) receptor to get into the cells to start an infection. Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. These inhibitors were discovered through an approach of in silico screening of available databases of bioactive peptides and polyphenolic compounds and the analysis of their docking modes. This process led to the selection of 9 compounds with optimal binding affinities to the target sites. The peptides (satpdb18674, satpdb18446, satpdb12488, satpdb14438, and satpdb28899) act on regions III and IV of the viral Spike protein and on its binding sites in GRP78. However, 4 polyphenols such as epigallocatechin gallate (EGCG), homoeriodictyol, isorhamnetin, and curcumin interact, in addition to the Spike protein and its binding sites in GRP78, with the ATPase domain of GRP78. Our work demonstrates that there are at least 2 approaches to block the spread of SARS-CoV-2 by preventing its fusion with the host cells via GRP78. url: https://doi.org/10.1177/1177932220965505 doi: 10.1177/1177932220965505 id: cord-281552-zfjy3m3i author: Alsaadi, Entedar A. J. title: Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus date: 2020-09-22 words: 4781.0 sentences: 205.0 pages: flesch: 49.0 cache: ./cache/cord-281552-zfjy3m3i.txt txt: ./txt/cord-281552-zfjy3m3i.txt summary: Here, we test E-derived peptides for membrane binding activity in vitro and confirm those identified as positive in the context of the full length protein expressed in two different cell types. Relative densitometry of the HSP and LSP bands revealed significant differences among the mutants with regard to their localisation to the different membrane fractions of E expressing insect cells ( Figure 5B ) and confirmed a role for the amphipathic MHV CoV E 50-64 peptide in membrane interaction. An amphipathic helix, EPTM, detected in the post-TM region of E, was suggested by bioinformatics analysis and assessed for direct membrane interaction in vitro by binding to GUVs. For comparison, the predicted E protein TM domain, ETM, and an established membrane active peptide from the influenza M2 protein were also included. Following expression of the complete E protein with mutations in the same identified peptide, altered membrane binding in two distinct cell types, mammalian and insect, was apparent. abstract: Coronaviruses (CoVs) are enveloped, positive sense, single strand RNA viruses that cause respiratory, intestinal and neurological diseases in mammals and birds. Following replication, CoVs assemble on intracellular membranes including the endoplasmic reticulum Golgi intermediate compartment (ERGIC) where the envelope protein (E) functions in virus assembly and release. In consequence, E potentially contains membrane-modifying peptides. To search for such peptides, the E coding sequence of Mouse Hepatitis Virus (MHV) was inspected for its amino acid conservation, proximity to the membrane and/or predicted amphipathic helices. Peptides identified in silico were synthesized and tested for membrane-modifying activity in the presence of giant unilamellar vesicles (GUVs) consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), sphingomyelin and cholesterol. To confirm the presence of membrane binding peptides identified in the context of a full-length E protein, the wild type and a number of mutants in the putative membrane binding peptide were expressed in Lenti-X-293T mammalian and insect cells, and the distribution of E antigen within the expressing cell was assessed. Our data identify a role for the post-transmembrane region of MHV E in membrane binding. url: https://www.ncbi.nlm.nih.gov/pubmed/32971895/ doi: 10.3390/v12091054 id: cord-004672-0lf5j8lo author: Anderson, Kevin title: Structural and physiological properties of mengovirus: Avirulent, hemagglutination-defective mutants express altered alpha (1 D) proteins and are adsorption-defective date: 1987 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Structural and physiological properties of two mutants of mengovirus, 205 and 280, were compared to those of wild-type virus to understand the molecular basis of changes exhibited in their biological function. Two dimensional gel electrophoresis of wild-type and mutant structural proteins revealed alterations in the isoelectric character of the alpha (1 D) protein of both mutant 205 and 280. These data suggest that alterations in the alpha (1 D) protein may be responsible for the phenotypic changes by the mutants. A delay in detectable virus-specified protein synthesis was exhibited in mutant-infected cells in comparison to wild-type. The amount of RNA synthesized in mutant- and revertant-infected cells was less than that synthesized in wild-type infected cells. Changes in virus-specified macro-molecular synthesis in mutant and revertant-infected cells reflected a decrease in the ability of the viruses to attach to cells. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086560/ doi: 10.1007/bf01313891 id: cord-312489-ywep0c08 author: Andoh, Kiyohiko title: Decreased neutralizing antigenicity in IBV S1 protein expressed from mammalian cells date: 2015-10-02 words: 5039.0 sentences: 246.0 pages: flesch: 43.0 cache: ./cache/cord-312489-ywep0c08.txt txt: ./txt/cord-312489-ywep0c08.txt summary: We evaluated the antigenicity of recombinant infectious bronchitis virus (IBV) S1 protein expressed in mammalian cells. Native S1 ELISA detected similar titers in the sera of animals immunized with recombinant S1 protein compared to those in sera of chickens immunized with inactivated virus (Fig. 6b ) (Control experiments (data not shown) demonstrated that mock and unvaccinated control groups did not differ from each other in VN and ELISA tests of anti-S1 activity.) These results indicated that while recombinant S1 protein retained antigenicity (the ability to induce antibodies against S1 protein), the resulting antibodies was decreased its neutralizing activity, in contrast to those induced by inactivated virus. The S1 glycoprotein but not the N or M proteins of avian infectious bronchitis virus induces protection in vaccinated chickens Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus abstract: We evaluated the antigenicity of recombinant infectious bronchitis virus (IBV) S1 protein expressed in mammalian cells. Recombinant S1 was expressed as a secreted protein fused with a trimerization motif peptide, then purified using Ni Sepharose. The purified protein was analyzed by Western blotting, mixed with oil adjuvant, and administered to 29-day-old specific-pathogen-free chickens. Six weeks after immunization, anti-IBV neutralizing titer and anti-S1 ELISA titer were determined; immunized chickens then were inoculated with IBV via the trachea and ciliary activity was observed. Results showed that the recombinant S1 protein was highly glycosylated, and the neutralizing antigenicity of recombinant S1 protein was lower than that of inactivated virus. However, anti-S1 ELISA indicated that the recombinant S1 protein induced antibodies against S1. These results suggest that the recombinant S1 may retain non-neutralizing epitopes but have unnatural glycosylation pattern and conformation, resulting in lacking neutralizing conformational epitopes. In conclusion, the neutralizing antigenicity of recombinant S1 protein expressed from mammalian cells was decreased, and was not sufficient to induce neutralizing antibodies. url: https://www.sciencedirect.com/science/article/pii/S0168170215002841 doi: 10.1016/j.virusres.2015.06.019 id: cord-010260-8lnpujip author: Anthonsen, Henrik W. title: The blind watchmaker and rational protein engineering date: 1994-08-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In the present review some scientific areas of key importance for protein engineering are discussed, such as problems involved in deducting protein sequence from DNA sequence (due to posttranscriptional editing, splicing and posttranslational modifications), modelling of protein structures by homology, NMR of large proteins (including probing the molecular surface with relaxation agents), simulation of protein structures by molecular dynamics and simulation of electrostatic effects in proteins (including pH-dependent effects). It is argued that all of these areas could be of key importance in most protein engineering projects, because they give access to increased and often unique information. In the last part of the review some potential areas for future applications of protein engineering approaches are discussed, such as non-conventional media, de novo design and nanotechnology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173218/ doi: 10.1016/0168-1656(94)90152-x id: cord-291210-ghjseynl author: Arbely, Eyal title: A Highly Unusual Palindromic Transmembrane Helical Hairpin Formed by SARS Coronavirus E Protein date: 2004-08-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The agent responsible for the recent severe acute respiratory syndrome (SARS) outbreak is a previously unidentified coronavirus. While there is a wealth of epidemiological studies, little if any molecular characterization of SARS coronavirus (SCoV) proteins has been carried out. Here we describe the molecular characterization of SCoV E protein, a critical component of the virus responsible for virion envelope morphogenesis. We conclusively show that SCoV E protein contains an unusually short, palindromic transmembrane helical hairpin around a previously unidentified pseudo-center of symmetry, a structural feature which seems to be unique to SCoV. The hairpin deforms lipid bilayers by way of increasing their curvature, providing for the first time a molecular explanation of E protein's pivotal role in viral budding. The molecular understanding of this critical component of SCoV may represent the beginning of a concerted effort aimed at inhibiting its function, and consequently, viral infectivity. url: https://www.ncbi.nlm.nih.gov/pubmed/15288785/ doi: 10.1016/j.jmb.2004.06.044 id: cord-272467-8heg5iql author: Armstrong, John title: Expression of coronavirus E1 and rotavirus VP10 membrane proteins from synthetic RNA date: 2004-02-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Some viruses acquire their envelopes by budding through internal membranes of their host cell. We have expressed the cloned cDNA for glycoproteins from two such viruses, the E1 protein of coronavirus, which buds in the Golgi region, and VP10 protein of rotavirus, which assembles in the endoplasmic reticulum. Messenger RNA was prepared from both cDNAs by using SP6 polymerase and either translated in vitro or injected into cultured CV1 cells or Xenopus oocytes. In CV1 cells, the El protein was localised to the Golgi region and VP10 protein to the endoplasmic reticulum. In Xenopus oocytes, the E1 protein acquired post‐translational modifications indistinguishable from the sialylated, O‐linked sugars found on viral protein, while the VP10 protein acquired endoglycosidase‐H‐sensitive N‐linked sugars, consistent with their localisation to the Golgi complex and endoplasmic reticulum, respectively. Thus the two proteins provide models with which to study targeting to each of these intracellular compartments. When the RNAs were expressed in matured, meiotic oocytes, the VP10 protein was modified as before, but the E1 protein was processed to a much lesser extent than in interphase oocytes, consistent with a cessation of vesicular transport during cell division. url: https://www.ncbi.nlm.nih.gov/pubmed/2448319/ doi: 10.1002/jcb.240350206 id: cord-341378-pw60qx7c author: Armstrong, John title: Sequence and topology of a model intracellular membrane protein, E1 glycoprotein, from a coronavirus date: 1984 words: 1578.0 sentences: 88.0 pages: flesch: 55.0 cache: ./cache/cord-341378-pw60qx7c.txt txt: ./txt/cord-341378-pw60qx7c.txt summary: In combination with a previous study of its assembly into the endoplasmic reticulum membrane(9), the sequence reveals several unusual features of the protein which may be related to its intracellular localization. In the eukaryotic cell, both secreted and plasma membrane proteins are synthesized at the endoplasmic reticulum, then transported, via the Golgi complex, to the ceU surface 1 -4. Here we present the primary structure of the protein, determined by analysis of eDNA clones prepared from viral mRNA. In combination with a previous stu''!} of its assembly into the endoplasmic reticulum membrane , the sequence reveals several unusual features of the protein which may be related to its intracellular localization. Thus, the El glycoprotein is potentially a convenient model for studying those features of a membrane protein that determine its arrest at a particular destination on the membrane transport pathway. abstract: In the eukaryotic cell, both secreted and plasma membrane proteins are synthesized at the endoplasmic reticulum, then transported, via the Golgi complex, to the cell surface(1–4). Each of the compartments of this transport pathway carries out particular metabolic functions(5–8), and therefore presumably contains a distinct complement of membrane proteins. Thus, mechanisms must exist for localizing such proteins to their respective destinations. However, a major obstacle to the study of such mechanisms is that the isolation and detailed analysis of such internal membrane proteins pose formidable technical problems. We have therefore used the E1 glycoprotein from coronavirus MHV-A59 as a viral model for this class of protein. Here we present the primary structure of the protein, determined by analysis of cDNA clones prepared from viral mRNA. In combination with a previous study of its assembly into the endoplasmic reticulum membrane(9), the sequence reveals several unusual features of the protein which may be related to its intracellular localization. url: https://www.ncbi.nlm.nih.gov/pubmed/6325918/ doi: 10.1038/308751a0 id: cord-336364-2ust3qoq author: Artigas, Laura title: In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm date: 2020-10-02 words: 5858.0 sentences: 295.0 pages: flesch: 45.0 cache: ./cache/cord-336364-2ust3qoq.txt txt: ./txt/cord-336364-2ust3qoq.txt summary: title: In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm This has provided 3 sets of proteins related with the infection process: 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lungcells infection set, and 3) acute respiratory distress (ARD) set. According to the findings by GUILDify, we confirm the effect of the combination of pirfenidone and melatonin in the entry points of the SARS-CoV-2 infection, specifically the neighbours of furin and GRP-78, and some proteins associated with ARD. 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lung-cells infection set, and 3) acute respiratory distress (ARD) set that is composed of 6 subsets (Alveolar macrophages, Monocytes, Neutrophils, Intermediate phase ARD, Late phase ARD and ARD cytokine storm). abstract: From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches. The drug combination of pirfenidone and melatonin has been identified as a candidate treatment that may contribute to reduce the virus infection. Starting from different drug targets the effect of the drugs converges on human proteins with a known role in SARS-CoV-2 infection cycle. Simultaneously, GUILDify v2.0 web server has been used as an alternative method to corroborate the effect of pirfenidone and melatonin against the infection of SARS-CoV-2. We have also predicted a potential therapeutic effect of the drug combination over the respiratory associated pathology, thus tackling at the same time two important issues in COVID-19. These evidences, together with the fact that from a medical point of view both drugs are considered safe and can be combined with the current standard of care treatments for COVID-19 makes this combination very attractive for treating patients at stage II, non-severe symptomatic patients with the presence of virus and those patients who are at risk of developing severe pulmonary complications. url: https://doi.org/10.1371/journal.pone.0240149 doi: 10.1371/journal.pone.0240149 id: cord-009959-erh8ggh3 author: BENTLEY, WILLIAM E. title: Development of an Efficient Bioprocess for Poultry Vaccines Using High‐density Insect Cell Culture date: 2006-12-17 words: 5803.0 sentences: 325.0 pages: flesch: 50.0 cache: ./cache/cord-009959-erh8ggh3.txt txt: ./txt/cord-009959-erh8ggh3.txt summary: Several general articles, manuals, and review articles have been published that describe both the expression system''" and novel process engineering aspects.%" In this work, we subdivide the entire bioprocess into three key areas: (1) metabolism of infected cells and specific heterologous protein yield; (2) bioreactor configuration and high cell density continuous culture; and (3) integration of expression and product separation. Caron el al." restored recombinant protein production at higher cell density by renewing the medium at the time of infection. High-level recombinant protein production in bioreactors using the baculovirus insect cell expression system Quantification of cell culture factors affecting recombinant protein yields in baculovirus-infected insect cells Effects of oxygen/glucose/glutamine feeding on insect cell baculovirus protein expression: A study on epoxide hydroxylase production Ecdysteroids increase the yield of recombinant protein produced in baculovirus insect cell expression system A continuous flow bioreactor system for the production of recombinant proteins using the insect cell-baculovirus expression system abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167613/ doi: 10.1111/j.1749-6632.1994.tb44387.x id: cord-000257-ampip7od author: Bagowski, Christoph P title: The Nature of Protein Domain Evolution: Shaping the Interaction Network date: 2010-08-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The proteomes that make up the collection of proteins in contemporary organisms evolved through recombination and duplication of a limited set of domains. These protein domains are essentially the main components of globular proteins and are the most principal level at which protein function and protein interactions can be understood. An important aspect of domain evolution is their atomic structure and biochemical function, which are both specified by the information in the amino acid sequence. Changes in this information may bring about new folds, functions and protein architectures. With the present and still increasing wealth of sequences and annotation data brought about by genomics, new evolutionary relationships are constantly being revealed, unknown structures modeled and phylogenies inferred. Such investigations not only help predict the function of newly discovered proteins, but also assist in mapping unforeseen pathways of evolution and reveal crucial, co-evolving inter- and intra-molecular interactions. In turn this will help us describe how protein domains shaped cellular interaction networks and the dynamics with which they are regulated in the cell. Additionally, these studies can be used for the design of new and optimized protein domains for therapy. In this review, we aim to describe the basic concepts of protein domain evolution and illustrate recent developments in molecular evolution that have provided valuable new insights in the field of comparative genomics and protein interaction networks. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945003/ doi: 10.2174/138920210791616725 id: cord-303494-tofch4j7 author: Bai, Juan title: Identification of VP1 peptides diagnostic of encephalomyocarditis virus from swine date: 2014-12-30 words: 3854.0 sentences: 198.0 pages: flesch: 57.0 cache: ./cache/cord-303494-tofch4j7.txt txt: ./txt/cord-303494-tofch4j7.txt summary: In order to map the minimal sequences of the epitopes recognized by McAbs, the series of truncated recombinant proteins were used in Western blot was to identify the reactivity of each of 10 anti-VP1 McAbs. The results showed that McAbs (6E11, 7A7 and 7C9) could reacted with fragments (F11, F9 and F3) containing the six amino acids V(2)ENAEK(7), but not reacted with the fragments with the deletion of any one of the six amino acids (F10, F7 and F8). Meanwhile, those purified truncated fragment proteins were used as the antigens in ELISA to detect the levels of those McAbs. The results showed that the OD 450 values of McAbs (6E11, 7A7 and 7C9) in F1, F3, F9 and F11 groups were significantly higher than those in F6, F7, F8 and F10 (p < 0.01) ( Figure 4A ). abstract: BACKGROUND: Encephalomyocarditis virus (EMCV) can cause myocarditis, respiratory failure, reproductive failure, and sudden death in pre-weaned piglets, which has been isolated in China. EMCV VP1 protein was one of the most important structural proteins and played an important role in the protective immunity. In this study, 10 monoclonal antibodies (McAbs) against EMCV VP1 were screened and identified. RESULTS: Epitope mapping results indicated that McAbs (6E11, 7A7, 7C9) specifically recognized the linear epitopes V(2)ENAEK(7), McAbs (1D1, 2A2, 5A1, 5A11, 5G1) recognized the epitope F(19)VAQPVY(25), and McAbs 1G8 and 3A9 recognized P(42)IGAFTVK(49). Protein sequence alignment of VP1 with 16 EMCV isolates indicated that the epitope F(19)VAQPVY(25) was conserved in all the reference strains. The epitopes P(42)IGAFTVK(49) and V(2)ENAEK(7) only had 1 or 2 variable amino acid among the reference strains. The 3D model analysis results showed that these epitopes presented as spheres were shown within the context of the complete particle. CONCLUSIONS: In this study, ten McAbs against EMCV VP1 were developed and three B-cells epitopes (2-7aa, 19-25aa and 42-49aa) were defined in VP1. All the results herein will promote the future investigations into the function of VP1 of EMCV and development of diagnostic methods of EMCV. url: https://doi.org/10.1186/s12985-014-0226-8 doi: 10.1186/s12985-014-0226-8 id: cord-256340-w4z5avld author: Bailer, SM title: Connecting viral with cellular interactomes date: 2009-07-24 words: 3649.0 sentences: 167.0 pages: flesch: 38.0 cache: ./cache/cord-256340-w4z5avld.txt txt: ./txt/cord-256340-w4z5avld.txt summary: Genome-scale screens for intraviral and virus–host protein interactions and the analysis of literature-curated datasets are able to provide a novel, comprehensive perspective of viruses, and virus-infected cells. Until now, large-scale interaction screens were predominantly performed with the yeast-two-hybrid (Y2H) system; however, alternative high-throughput technologies detecting binary protein interactions or protein complexes have been developed. The Y2H system as the standard assay for the evaluation of interactomes Essentially all high-throughput approaches to identify binary protein interactions on a genome-scale currently rely on the Gal4-based yeast-two-hybrid (Y2H) system ( Figure 1 ) developed in 1989 [1] . Despite certain limitations the Y2H system is used by the majority of groups because of its enormous efficacy and the data discussed in this review are all based on Y2H screens as all currently published large-scale studies on intraviral or virus-host protein interactions are based on them. More recent approaches on intraviral interactomes include several members of the herpesvirus family [15 ,16 ,19 Scheme of HSV-1 virus particle with protein interactions detected in a genome-wide Y2H screen. abstract: Genome-scale screens for intraviral and virus–host protein interactions and the analysis of literature-curated datasets are able to provide a novel, comprehensive perspective of viruses, and virus-infected cells. Until now, large-scale interaction screens were predominantly performed with the yeast-two-hybrid (Y2H) system; however, alternative high-throughput technologies detecting binary protein interactions or protein complexes have been developed. Although many of the previous studies suffer from a rather poor validation of the results and few biological implications, these technologies potentially lead to a plethora of novel hypotheses. Here, we will give an overview of current approaches and their technical limitations, present recent examples and novel developments. url: https://doi.org/10.1016/j.mib.2009.06.004 doi: 10.1016/j.mib.2009.06.004 id: cord-319754-5isw53wl author: Balgoma, David title: Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update date: 2020-08-31 words: 12092.0 sentences: 541.0 pages: flesch: 41.0 cache: ./cache/cord-319754-5isw53wl.txt txt: ./txt/cord-319754-5isw53wl.txt summary: Some viruses may use different entry mechanisms, this feature being likely dependent upon the membrane lipid composition of the host cell they infect as well as the particular cell surface factor attachment used. The question regarding whether the lipid-raft domains may serve as platforms to concentrate the proteins required for viral entry and, even though some evidence exists, to activate signaling pathways inside the host cell still remains unsolved. More recently, a Ca 2+ -dependent pathway of infection by the Rubella virus (RuV, Rubivirus family, Togaviridae) was demonstrated to proceed through direct binding of the fusion loop in the viral E1 protein to SM/cholesterol-enriched membranes [49] . More recently, a Ca 2+ -dependent pathway of infection by the Rubella virus (RuV, Rubivirus family, Togaviridae) was demonstrated to proceed through direct binding of the fusion loop in the viral E1 protein to SM/cholesterol-enriched membranes [49] . abstract: The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focused on the function of proteins. Here, we review the role of cholesterol and other lipids in ssRNA+ infection. url: https://www.ncbi.nlm.nih.gov/pubmed/32878290/ doi: 10.3390/metabo10090356 id: cord-342189-ya05m58o author: Banerjee, Abhik K. title: SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses date: 2020-10-08 words: 11469.0 sentences: 647.0 pages: flesch: 55.0 cache: ./cache/cord-342189-ya05m58o.txt txt: ./txt/cord-342189-ya05m58o.txt summary: Here, we comprehensively define the interactions between each SARS-CoV-2 protein and human RNAs. We show that 10 viral proteins form highly specific interactions with mRNAs or ncRNAs, including those involved in progressive steps of host cell protein production. We show J o u r n a l P r e -p r o o f 5 that NSP16 binds to the mRNA recognition domains of the U1 and U2 RNA components of the spliceosome and acts to suppress global mRNA splicing in SARS-CoV-2-infected human cells. We identified several pathogenic functions of SARS-CoV-2 in human cells -including global inhibition of host mRNA splicing, protein translation, and membrane protein trafficking -and described the molecular mechanisms by which the virus acts to disrupt these essential cell processes. abstract: SARS-CoV-2 is a recently identified coronavirus that causes the respiratory disease known as COVID-19. Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the Signal Recognition Particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses. url: https://api.elsevier.com/content/article/pii/S0092867420313106 doi: 10.1016/j.cell.2020.10.004 id: cord-356064-q56jnhss author: Bartel, Sebastian title: Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides date: 2011-08-01 words: 6164.0 sentences: 314.0 pages: flesch: 45.0 cache: ./cache/cord-356064-q56jnhss.txt txt: ./txt/cord-356064-q56jnhss.txt summary: title: Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides In this report the proteome of HEK293 cells infected with Vaccinia Virus strain IHD-W was analyzed by 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS in a bottom-up approach. Derivatization of peptides with 4-sulfophenyl isothiocyanate (SPITC) carried out on ZipTipμ-C18 columns enabled protein identification via the peptides'' primary sequence, providing improved s/n ratios as well as signal intensities of the PSD spectra. The E3L gene product has been identified in HEK 293 cells infected with active VACV IHD-W, which is in correlation to proteome analysis of VACV virions that indicate that the putative double-stranded RNA binding protein (D-1) is not present in the virion but is expressed in the early replication phase. Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides abstract: BACKGROUND: Despite the successful eradication of smallpox by the WHO-led vaccination programme, pox virus infections remain a considerable health threat. The possible use of smallpox as a bioterrorism agent as well as the continuous occurrence of zoonotic pox virus infections document the relevance to deepen the understanding for virus host interactions. Since the permissiveness of pox infections is independent of hosts surface receptors, but correlates with the ability of the virus to infiltrate the antiviral host response, it directly depends on the hosts proteome set. In this report the proteome of HEK293 cells infected with Vaccinia Virus strain IHD-W was analyzed by 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS in a bottom-up approach. RESULTS: The cellular and viral proteomes of VACV IHD-W infected HEK293 cells, UV-inactivated VACV IHD-W-treated as well as non-infected cells were compared. Derivatization of peptides with 4-sulfophenyl isothiocyanate (SPITC) carried out on ZipTipμ-C18 columns enabled protein identification via the peptides' primary sequence, providing improved s/n ratios as well as signal intensities of the PSD spectra. The expression of more than 24 human proteins was modulated by the viral infection. Effects of UV-inactivated and infectious viruses on the hosts' proteome concerning energy metabolism and proteins associated with gene expression and protein-biosynthesis were quite similar. These effects might therefore be attributed to virus entry and virion proteins. However, the modulation of proteins involved in apoptosis was clearly correlated to infectious viruses. CONCLUSIONS: The proteome analysis of infected cells provides insight into apoptosis modulation, regulation of cellular gene expression and the regulation of energy metabolism. The confidence of protein identifications was clearly improved by the peptides' derivatization with SPITC on a solid phase support. Some of the identified proteins have not been described in the context of poxvirus infections before and need to be further characterised to identify their meaning for apoptosis modulation and pathogenesis. url: https://doi.org/10.1186/1743-422x-8-380 doi: 10.1186/1743-422x-8-380 id: cord-262043-66qle52a author: Basit, Abdul title: Truncated human angiotensin converting enzyme 2; a potential inhibitor of SARS-CoV-2 spike glycoprotein and potent COVID-19 therapeutic agent date: 2020-05-20 words: 4866.0 sentences: 275.0 pages: flesch: 55.0 cache: ./cache/cord-262043-66qle52a.txt txt: ./txt/cord-262043-66qle52a.txt summary: Spike (S) glycoprotein is the structural protein of SARS-CoV-2 located on the envelope surface, involve in interaction with angiotensin converting enzyme 2 (ACE2), a cell surface receptor, followed by entry into the host cell. The protein-protein docking and molecular dynamic simulation showed that tACE2 has higher binding affinity for RBD and form more stabilized complex with RBD than the intact ACE2. We designed a truncated version (tACE2) of ACE2 receptor covering the binding residues and performed protein-protein docking and molecular dynamic simulations to analyze its binding affinity for RBD and complex stability. Based on the HADDOCK score and the docking RMSD value, the docked complexes of ACE2 and tACE2 with RBD were analyzed for binding affinity DG (kcal mol À1 ) and stability using protein binding energy prediction (PRODIGY) server (Xue et al., 2016) . abstract: The current pandemic of Covid-19 caused by SARS-CoV-2 is continued to spread globally and no potential drug or vaccine against it is available. Spike (S) glycoprotein is the structural protein of SARS-CoV-2 located on the envelope surface, involve in interaction with angiotensin converting enzyme 2 (ACE2), a cell surface receptor, followed by entry into the host cell. Thereby, blocking the S glycoprotein through potential inhibitor may interfere its interaction with ACE2 and impede its entry into the host cell. Here, we present a truncated version of human ACE2 (tACE2), comprising the N terminus region of the intact ACE2 from amino acid position 21-119, involved in binding with receptor binding domain (RBD) of SARS-CoV-2. We analyzed the in-silico potential of tACE2 to compete with intact ACE2 for binding with RBD. The protein-protein docking and molecular dynamic simulation showed that tACE2 has higher binding affinity for RBD and form more stabilized complex with RBD than the intact ACE2. Furthermore, prediction of tACE2 soluble expression in E. coli makes it a suitable candidate to be targeted for Covid-19 therapeutics. This is the first MD simulation based findings to provide a high affinity protein inhibitor for SARS-CoV-2 S glycoprotein, an important target for drug designing against this unprecedented challenge. Communicated by Ramaswamy H. Sarma url: https://doi.org/10.1080/07391102.2020.1768150 doi: 10.1080/07391102.2020.1768150 id: cord-330337-d41imvo7 author: Basu, Souradip title: Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins date: 2020-10-20 words: 6428.0 sentences: 311.0 pages: flesch: 52.0 cache: ./cache/cord-330337-d41imvo7.txt txt: ./txt/cord-330337-d41imvo7.txt summary: Our observations and analysis direct us to identify that all the major mutations have a negative impact in context of stability of the viral proteins under study and the mutant proteins suffer both structural and functional alterations as a result of the mutations. The secondary structure of the wild type and the mutant proteins along with their degree of disordered residues and accessible surface area was predicted using the primary sequence of the protein. Each of the seven proteins were assigned a score of either ''-1'' or ''0'', for each of the four computational tools used for epitope prediction, where ''-1'' corresponds to any change in number or binding efficacy of antigenic determinants, that may have surfaced because of mutation and ''0'' corresponds to no changes between wild type and mutant forms. I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure abstract: The SARS-CoV-2 is a positive stranded RNA virus with a genome size of ~29.9 kilobase pairs which spans 29 open reading frames. Studies have revealed that the genome encodes about 16 non-structural proteins (nsp), four structural proteins, and six or seven accessory proteins. Based on prevalent knowledge on SARS-CoV and other coronaviruses, functions have been assigned for majority of the proteins. While, researchers across the globe are engrossed in identifying a potential pharmacological intervention to control the viral outbreak, none of the work has come up with new antiviral drugs or vaccines yet. One possible approach that has shown some positive results is by treating infected patients with the plasma collected from convalescent COVID-19 patients. Several vaccines around the world have entered their final trial phase in humans and we expect that these will in time be available for application to worldwide population to combat the disease. In this work we analyse the effect of prevalent mutations in the major pathogenesis related proteins of SARS-COV2 and attempt to pinpoint the effects of those mutations on the structural stability of the proteins. Our observations and analysis direct us to identify that all the major mutations have a negative impact in context of stability of the viral proteins under study and the mutant proteins suffer both structural and functional alterations as a result of the mutations. Our binary scoring scheme identifies L84S mutation in ORF8 as the most disruptive of the mutations under study. We believe that, the virus is under the influence of an evolutionary phenomenon similar to Muller’s ratchet where the continuous accumulation of these mutations is making the virus less virulent which may also explain the reduction in fatality rates worldwide. url: https://doi.org/10.1101/2020.10.20.347021 doi: 10.1101/2020.10.20.347021 id: cord-018265-twp33bb6 author: Becker, Pablo D. title: Community-acquired pneumonia: paving the way towards new vaccination concepts date: 2007 words: 14121.0 sentences: 697.0 pages: flesch: 36.0 cache: ./cache/cord-018265-twp33bb6.txt txt: ./txt/cord-018265-twp33bb6.txt summary: A live vaccine based on a master virus strain developed at the Institute of Applied Microbiology (Austria) by growing wild influenza virus in Vero cells at 25°C was also demonstrated to be safe, well-tolerated and immunogenic after intranasal immunization in young adults [18]. Candidate vaccines should be able to replicate and induce a protective immune response in young infants, even in the presence of maternally acquired antibodies. This demonstrates that antibodies play a major role in protection against this disease, whereas T-cell immunity targeted to internal viral proteins appears to contribute to clearance. The second generation of PS-based conjugate vaccines stimulates stronger antibody responses, even in infants, young children and immune deficient individuals, as well as immunological memory. The resulting proteins are then used to perform immunological and/or functional studies to select the most promising candidates (e.g., able to induce the production of microbicidal or neutralizing antibodies, capacity to confer protective immunity). abstract: Despite the availability of antimicrobial agents and vaccines, community-acquired pneumonia remains a serious problem. Severe forms tend to occur in very young children and among the elderly, since their immune competence is eroded by immaturity and immune senescence, respectively. The main etiologic agents differ according to patient age and geographic area. Streptococcus pneumoniae, Haemophilus influenzae, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV-3) are the most important pathogens in children, whereas influenza viruses are the leading cause of fatal pneumonia in the elderly. Effective vaccines are available against some of these organisms. However, there are still many agents against which vaccines are not available or the existent ones are suboptimal. To tackle this problem, empiric approaches are now being systematically replaced by rational vaccine design. This is facilitated by the growing knowledge in the fields of immunology, microbial pathogenesis and host response to infection, as well as by the availability of sophisticated strategies for antigen selection, potent immune modulators and efficient antigen delivery systems. Thus, a new generation of vaccines with improved safety and efficacy profiles compared to old and new agents is emerging. In this chapter, an overview is provided about currently available and new vaccination concepts. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123104/ doi: 10.1007/978-3-7643-7563-8_10 id: cord-300418-s4wt5gim author: Bedford, Lynn title: Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets date: 2010-12-10 words: 13080.0 sentences: 640.0 pages: flesch: 37.0 cache: ./cache/cord-300418-s4wt5gim.txt txt: ./txt/cord-300418-s4wt5gim.txt summary: In this Review, we first provide an overview of the enzyme classes in the UPS and UBL pathways that represent potential therapeutic targets, highlighting considerations that are important for drug discovery and recent progress in the development of small-molecule inhibitors. Studies using NF-κB-dependent human cancer models have demonstrated increased levels of the CRL1β TRCP substrate pIκBα and inhibition of NF-κB activity and apoptosis 116, 117 , suggesting the feasibility of NAE inhibition for the treatment of disease that is associated with constitutively active NF-κB signalling 112 The recent discovery of the importance of linear ubiquitin chains in NF-κB activation extends the complexity of the regulation of the system. As expected, ubiquitin-dependent processes, including the degradation of ubiquitylated proteins by the 26S proteasome, by autophagy and in the endosome-lysosome pathway, have central roles in neuronal development, homeostasis and disease. abstract: The ubiquitin–proteasome system (UPS) and ubiquitin-like protein (UBL) conjugation pathways are integral to cellular protein homeostasis. The growing recognition of the fundamental importance of these pathways to normal cell function and in disease has prompted an in-depth search for small-molecule inhibitors that selectively block the function of these pathways. However, our limited understanding of the molecular mechanisms and biological consequences of UBL conjugation is a significant hurdle to identifying drug-like inhibitors of enzyme targets within these pathways. Here, we highlight recent advances in understanding the role of some of these enzymes and how these new insights may be the key to developing novel therapeutics for diseases including immuno-inflammatory disorders, cancer, infectious diseases, cardiovascular disease and neurodegenerative disorders. url: https://www.ncbi.nlm.nih.gov/pubmed/21151032/ doi: 10.1038/nrd3321 id: cord-319614-4qi59pbz author: Benej, Martin title: Quantitative Proteomics Reveal Peroxiredoxin Perturbation Upon Persistent Lymphocytic Choriomeningitis Virus Infection in Human Cells date: 2019-10-25 words: 8900.0 sentences: 479.0 pages: flesch: 45.0 cache: ./cache/cord-319614-4qi59pbz.txt txt: ./txt/cord-319614-4qi59pbz.txt summary: Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. Increased levels of ROS were accompanied by changes in the pattern of telomere restriction fragments (TRFs) in infected cells and mediated activation of hypoxia-inducible transcription factor-1 (HIF-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. These data suggest that LCMV maintains its replication in persistently infected cells by regulating redox signaling through modulation of local levels of H 2 O 2 and subsequent activation of cellular processes that it uses for its own benefit. Notably, the treatment with antioxidants also resulted in reduced levels of viral NP in HeLa, as well as in A549 LCMV-infected cells, suggesting a link between ROS-dependent signaling and virus replication (Figures 7B,D and Supplementary Figure S2B ). abstract: Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. In order to shed more light on these processes, two-dimensional differential in-gel electrophoresis (2D-DIGE) and MALDI-TOF tandem mass spectrometry were used to determine the proteome response of the HeLa cell line to persistent LCMV infection. Quantitative analysis revealed 24 differentially abundant proteins. Functional analysis showed that LCMV-responsive proteins were primarily involved in metabolism, stress, and the defense response. Among identified proteins, we discovered significant changes for peroxiredoxins, a family of antioxidant enzymes. Decreased amount of these antioxidant proteins correlated with elevation of reactive oxygen species (ROS) in infected cells. Increased levels of ROS were accompanied by changes in the pattern of telomere restriction fragments (TRFs) in infected cells and mediated activation of hypoxia-inducible transcription factor-1 (HIF-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Moreover, treatment with antioxidants resulted in reduced levels of viral nucleoprotein, indicating a connection between ROS-dependent signaling and viral replication. url: https://www.ncbi.nlm.nih.gov/pubmed/31708904/ doi: 10.3389/fmicb.2019.02438 id: cord-274366-t138l6px author: Benetti, Elisa title: ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population date: 2020-07-17 words: 4525.0 sentences: 247.0 pages: flesch: 49.0 cache: ./cache/cord-274366-t138l6px.txt txt: ./txt/cord-274366-t138l6px.txt summary: Taking advantage of the Network of Italian Genomes (NIG), a consortium established to generate a public database (NIG-db) containing aggregate variant frequencies data for the Italian population (http://www.nig.cineca.it/), here we describe the genetic variation of ACE2 in the Italian population, one of the newly affected countries by the SARS-CoV-2 outbreak causing COVID-19. In order to shed light on the role of ACE2 variants on interindividual variability and susceptibility to COVID-19 in Italian population we performed WES analysis on a cohort of 131 patients and 258 controls who agreed in participating to the study (see "Materials and methods"). These variants which surround residual essentials for the SARS-CoV-2 spike protein binding were predicted to likely affect the cleavage-dependent virion intake, such as the polymorphic c.2158A>G p.(Asn720Asp) (allele frequency 0.011) which lies four amino acids from the cleavage sequence of TMPRSS2 or to have a substantial impact on protein structure and spike protein interaction by MD simulation (Fig. 3a) . abstract: In December 2019, an initial cluster of interstitial bilateral pneumonia emerged in Wuhan, China. A human-to-human transmission was assumed and a previously unrecognized entity, termed coronavirus disease-19 (COVID-19) due to a novel coronavirus (SARS-CoV-2) was described. The infection has rapidly spread out all over the world and Italy has been the first European country experiencing the endemic wave with unexpected clinical severity in comparison with Asian countries. It has been shown that SARS-CoV-2 utilizes angiotensin converting enzyme 2 (ACE2) as host receptor and host proteases for cell surface binding and internalization. Thus, a predisposing genetic background can give reason for interindividual disease susceptibility and/or severity. Taking advantage of the Network of Italian Genomes (NIG), here we mined whole-exome sequencing data of 6930 Italian control individuals from five different centers looking for ACE2 variants. A number of variants with a potential impact on protein stability were identified. Among these, three more common missense changes, p.(Asn720Asp), p.(Lys26Arg), and p.(Gly211Arg) were predicted to interfere with protein structure and stabilization. Rare variants likely interfering with the internalization process, namely p.(Leu351Val) and p.(Pro389His), predicted to interfere with SARS-CoV-2 spike protein binding, were also observed. Comparison of ACE2 WES data between a cohort of 131 patients and 258 controls allowed identifying a statistically significant (P value < 0.029) higher allelic variability in controls compared with patients. These findings suggest that a predisposing genetic background may contribute to the observed interindividual clinical variability associated with COVID-19, allowing an evidence-based risk assessment leading to personalized preventive measures and therapeutic options. url: https://www.ncbi.nlm.nih.gov/pubmed/32681121/ doi: 10.1038/s41431-020-0691-z id: cord-314746-1o0rf0ii author: Bergasa-Caceres, Fernando title: Interdiction of Protein Folding for Therapeutic Drug Development in SARS CoV-2 date: 2020-08-10 words: 5038.0 sentences: 304.0 pages: flesch: 56.0 cache: ./cache/cord-314746-1o0rf0ii.txt txt: ./txt/cord-314746-1o0rf0ii.txt summary: [Image: see text] In this article, we predict the folding initiation events of the ribose phosphatase domain of protein Nsp3 and the receptor binding domain of the spike protein from the severe acute respiratory syndrome (SARS) coronavirus-2. The identification of the primary contacts along the folding pathway of viral proteins constitutes an important result for at least two reasons: (a) the sequences of the specific segments involved in the primary contacts provide a template to specify candidate peptide drugs of inhibitory effect with the maximum possible contact affinity to compete with the natural folding mechanism; and (b) it provides insight for further investigation into the subsequent folding steps leading to a fully functional viral protein, potentially providing for additional FITRs. The fact that the primary contact is defined by the interaction between two well defined amino acid sequences suggests that a strategy to develop FITR-based therapeutic drugs could be one utilizing trial peptide drugs as suggested above. abstract: [Image: see text] In this article, we predict the folding initiation events of the ribose phosphatase domain of protein Nsp3 and the receptor binding domain of the spike protein from the severe acute respiratory syndrome (SARS) coronavirus-2. The calculations employ the sequential collapse model and the crystal structures to identify the segments involved in the initial contact formation events of both viral proteins. The initial contact locations may provide good targets for therapeutic drug development. The proposed strategy is based on a drug binding to the contact location, thereby aiming to prevent protein folding. Peptides are suggested as a natural choice for such protein folding interdiction drugs. url: https://www.ncbi.nlm.nih.gov/pubmed/32790379/ doi: 10.1021/acs.jpcb.0c03716 id: cord-103320-2rpr7aph author: Bhandari, Bikash K. title: Solubility-Weighted Index: fast and accurate prediction of protein solubility date: 2020-03-26 words: 4889.0 sentences: 333.0 pages: flesch: 50.0 cache: ./cache/cord-103320-2rpr7aph.txt txt: ./txt/cord-103320-2rpr7aph.txt summary: Results We have discovered that global structural flexibility, which can be modeled by normalised B-factors, accurately predicts the solubility of 12,216 recombinant proteins expressed in Escherichia coli. Protein solubility, at least in part, depends upon extrinsic factors such as ionic strength, temperature and pH, as well as intrinsic factors-the physicochemical properties of the protein sequence and structure, including molecular weight, amino acid composition, hydrophobicity, aromaticity, isoelectric point, structural propensities and the polarity of surface residues (Wilkinson and Harrison 1991; Chiti et al. 2003 ) Among these sets of B-factors, sequence composition scoring using the most recently published set of normalised B-factors produced the highest AUC score ( To improve the prediction accuracy of solubility, we iteratively refined the weights of amino acid residues using the Nelder-Mead optimisation algorithm (Nelder and Mead 1965) . To understand the properties of soluble and insoluble proteins, we determined the enrichment of amino acid residues in the PSI:Biology targets relative to the eSOL sequences (see Methods). abstract: Motivation Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can therefore be purified. Results We have discovered that global structural flexibility, which can be modeled by normalised B-factors, accurately predicts the solubility of 12,216 recombinant proteins expressed in Escherichia coli. We have optimised B-factors, and derived a new set of values for solubility scoring that further improves prediction accuracy. We call this new predictor the ‘Solubility-Weighted Index’ (SWI). Importantly, SWI outperforms many existing protein solubility prediction tools. Furthermore, we have developed ‘SoDoPE’ (Soluble Domain for Protein Expression), a web interface that allows users to choose a protein region of interest for predicting and maximising both protein expression and solubility. Availability The SoDoPE web server and source code are freely available at https://tisigner.com/sodope and https://github.com/Gardner-BinfLab/TISIGNER-ReactJS, respectively. The code and data for reproducing our analysis can be found at https://github.com/Gardner-BinfLab/SoDoPE_paper2020. url: https://doi.org/10.1101/2020.02.15.951012 doi: 10.1101/2020.02.15.951012 id: cord-323358-05bk91lm author: Bhaskar, Sathyamoorthy title: Engineering protein nanocages as carriers for biomedical applications date: 2017-04-07 words: 9541.0 sentences: 557.0 pages: flesch: 39.0 cache: ./cache/cord-323358-05bk91lm.txt txt: ./txt/cord-323358-05bk91lm.txt summary: We review natural and synthetic protein nanocages that have been modified using chemical and genetic engineering techniques to impart non-natural functions that are responsive to the complex cellular microenvironment of malignant cells while delivering molecular cargos with improved efficiencies and minimal toxicity. 1, 3 Examples of naturederived nanocarriers include protein nanocages such as viruses, ferritin and many others that are formed by the self-assembly of protein subunits, resulting in a cage-like structure. 8 In this review, we focus on natural and synthetic protein scaffolds engineered with specific functional groups to impart non-native functions, including aiding the delivery of active molecules through targeting of malignant cells and overcoming cellular barriers. 3 In addition to cell targeting ability and gene delivery efficiency, these protein-based multifaceted systems have highly ordered spatial configurations, and the stability and functionality of these materials have already been established through intensive research with advances in understanding virus infection, replication and assembly pathways. abstract: Protein nanocages have been explored as potential carriers in biomedicine. Formed by the self-assembly of protein subunits, the caged structure has three surfaces that can be engineered: the interior, the exterior and the intersubunit. Therapeutic and diagnostic molecules have been loaded in the interior of nanocages, while their external surfaces have been engineered to enhance their biocompatibility and targeting abilities. Modifications of the intersubunit interactions have been shown to modulate the self-assembly profile with implications for tuning the molecular release. We review natural and synthetic protein nanocages that have been modified using chemical and genetic engineering techniques to impart non-natural functions that are responsive to the complex cellular microenvironment of malignant cells while delivering molecular cargos with improved efficiencies and minimal toxicity. url: https://doi.org/10.1038/am.2016.128 doi: 10.1038/am.2016.128 id: cord-252536-gfx4cq03 author: Bieniossek, Christoph title: MultiBac: expanding the research toolbox for multiprotein complexes date: 2011-12-07 words: 7120.0 sentences: 354.0 pages: flesch: 39.0 cache: ./cache/cord-252536-gfx4cq03.txt txt: ./txt/cord-252536-gfx4cq03.txt summary: It consists of an array of small synthetic DNA plasmids, an engineered baculovirus genome derived from the Autographa californica nuclear polyhedrosis virus (AcNPV; see Glossary) that is used to infect cells of the caterpillar Spodoptera frugiperda, and a set of protocols detailing every step from gene insertion into the plasmids to production of protein complexes in cultured insect cells [19, 20] . Donors and acceptors contain a resistance marker, a short imperfect inverted repeat (LoxP), an expression cassette consisting of a baculoviral promoter (p10 or polh), a DNA segment for inserting heterologous genes, and an efficient signal for eukaryotic polyadenylation (Figure 1a ). Two outstanding examples of the utility of MultiBac are the elegant production of the entire anaphase promoting complex, APC/Ca large (1.1 MDa) 13-subunit multiprotein assembly that regulates defined cell cycle transitions [34] and the recent crystal structure elucidation of the Mediator head modulea transcription factor complex that is essential for the expression of class II genes in eukaryotes [35] . abstract: Protein complexes composed of many subunits carry out most essential processes in cells and, therefore, have become the focus of intense research. However, deciphering the structure and function of these multiprotein assemblies imposes the challenging task of producing them in sufficient quality and quantity. To overcome this bottleneck, powerful recombinant expression technologies are being developed. In this review, we describe the use of one of these technologies, MultiBac, a baculovirus expression vector system that is particularly tailored for the production of eukaryotic multiprotein complexes. Among other applications, MultiBac has been used to produce many important proteins and their complexes for their structural characterization, revealing fundamental cellular mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/22154230/ doi: 10.1016/j.tibs.2011.10.005 id: cord-000012-p56v8wi1 author: Bigot, Yves title: Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis date: 2008-09-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Female endoparasitic ichneumonid wasps inject virus-like particles into their caterpillar hosts to suppress immunity. These particles are classified as ichnovirus virions and resemble ascovirus virions, which are also transmitted by parasitic wasps and attack caterpillars. Ascoviruses replicate DNA and produce virions. Polydnavirus DNA consists of wasp DNA replicated by the wasp from its genome, which also directs particle synthesis. Structural similarities between ascovirus and ichnovirus particles and the biology of their transmission suggest that ichnoviruses evolved from ascoviruses, although molecular evidence for this hypothesis is lacking. RESULTS: Here we show that a family of unique pox-D5 NTPase proteins in the Glypta fumiferanae ichnovirus are related to three Diadromus pulchellus ascovirus proteins encoded by ORFs 90, 91 and 93. A new alignment technique also shows that two proteins from a related ichnovirus are orthologs of other ascovirus virion proteins. CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. We also discuss the limits of this evidence through complementary studies, which revealed that passive lateral transfer of viral genes among polydnaviral, bacterial, and wasp genomes may have occurred repeatedly through an intimate coupling of both recombination and replication of viral genomes during evolution. The impact of passive lateral transfers on evolutionary relationships between polydnaviruses and viruses with large double-stranded genomes is considered in the context of the theory of symbiogenesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567993/ doi: 10.1186/1471-2148-8-253 id: cord-318551-c1qr27lg author: Boguszewska‐Chachulska, Anna M. title: Rna Viruses Redirect Host Factors to Better Amplify Their Genome date: 2005-12-29 words: 10673.0 sentences: 511.0 pages: flesch: 44.0 cache: ./cache/cord-318551-c1qr27lg.txt txt: ./txt/cord-318551-c1qr27lg.txt summary: (Adapted with permission from Pasternak et al., 2001.) Transcription of segmented (À) strand RNA viruses such as the Orthomyxoviridae, Arenaviridae, Bunyaviridae, and Tenuiviruses requires a primer to initiate synthesis of the mRNAs. This is achieved by cap-snatching in which the replicase complex, or a protein thereof, binds to the 5 0 region of cell mRNAs, cleaves off the cap together with generally 7-15 nucleotides from the 5 0 end of the cell mRNA, and uses this fragment as a primer to initiate synthesis of the viral mRNAs (Bouloy et al., 1978; Nguyen and Haenni, 2003) . (1996) PV, poliovirus; MHV, mouse hepatitis virus; WNV, West Nile virus; BVDV, bovine viral diarrhea virus; HPIV-3, human parainfluenza virus-3; IG (À), intergenic region in (À) RNA; UTR, untranslated region; Leader RNA (À), 3'' end of (À) RNA; Leader RNA (þ), 5'' end of (þ) RNA; HF, host factor; PCBP, poly(C)-binding protein; PABP, poly(A)-binding protein; hnRNP A1, heterogeneous nuclear ribonucleoprotein A1; PTB, polypyrimidine tract-binding protein; TIA-1, T-cell-activated intracellular antigen; TIAR, TIA-1-related; RHA, RNA helicase A; GAPDH, glyceraldehyde-3-phosphate dehydrogenase. abstract: This chapter provides an updated view of the host factors that are, at present, believed to participate in replication/transcription of RNA viruses. One of the major hurdles faced when attempting to identify host factors specifically involved in viral RNA replication/transcription is how to discriminate these factors from those involved in translation. Several of the host factors shown to affect viral RNA synthesis are factors known to be involved in protein synthesis, for example, translation factors. In addition, some of the factors identified to date appear to influence viral RNA amplification as well as viral protein synthesis, and translation and replication are frequently tightly associated. Several specific host factors actively participating in viral RNA transcription/replication have been identified and the regions of host protein/replicase or host protein/viral RNA interaction have been determined. The chapter centers exclusively on those factors that appear functionally important for viral amplification. It presents a list of the viruses for which a specific host factor associates with the polymerase, affecting viral genome amplification. It also indicates the usually accepted cell function of the factor and the viral polymerase or polymerase subunit to which the host factor binds. url: https://www.sciencedirect.com/science/article/pii/S0065352705650026 doi: 10.1016/s0065-3527(05)65002-6 id: cord-268326-sbz3uk5h author: Bonam, Srinivasa Reddy title: Lysosomes as a therapeutic target date: 2019-09-02 words: 17899.0 sentences: 839.0 pages: flesch: 37.0 cache: ./cache/cord-268326-sbz3uk5h.txt txt: ./txt/cord-268326-sbz3uk5h.txt summary: With a focus on lysosomal dysfunction in autoimmune disorders and neurodegenerative diseases — including lupus, rheumatoid arthritis, multiple sclerosis, Alzheimer disease and Parkinson disease — this Review critically analyses progress and opportunities for therapeutically targeting lysosomal proteins and processes, particularly with small molecules and peptide drugs. Alterations in lysosomal functions, either in the fusion processes involved in the general pathways mentioned above or related to the function of lyso somal enzymes and non enzymatic proteins, can result in broad detrimental effects, including failure to clear potentially toxic cellular waste, inflammation, apopto sis and dysregulation of cellular signalling 8 . abstract: Lysosomes are membrane-bound organelles with roles in processes involved in degrading and recycling cellular waste, cellular signalling and energy metabolism. Defects in genes encoding lysosomal proteins cause lysosomal storage disorders, in which enzyme replacement therapy has proved successful. Growing evidence also implicates roles for lysosomal dysfunction in more common diseases including inflammatory and autoimmune disorders, neurodegenerative diseases, cancer and metabolic disorders. With a focus on lysosomal dysfunction in autoimmune disorders and neurodegenerative diseases — including lupus, rheumatoid arthritis, multiple sclerosis, Alzheimer disease and Parkinson disease — this Review critically analyses progress and opportunities for therapeutically targeting lysosomal proteins and processes, particularly with small molecules and peptide drugs. url: https://doi.org/10.1038/s41573-019-0036-1 doi: 10.1038/s41573-019-0036-1 id: cord-001567-3bw7jbzq author: Borlak, Jürgen title: Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events date: 2015-02-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is on the rise and the sixth most common cancer worldwide. To combat HCC effectively research is directed towards its early detection and the development of targeted therapies. Given the fact that epidermal growth factor (EGF) is an important mitogen for hepatocytes we searched for disease regulated proteins to improve an understanding of the molecular pathogenesis of EGF induced HCC. Disease regulated proteins were studied by 2DE MALDI-TOF/TOF and a transcriptomic approach, by immunohistochemistry and advanced bioinformatics. RESULTS: Mapping of EGF induced liver cancer in a transgenic mouse model identified n = 96 (p < 0.05) significantly regulated proteins of which n = 54 were tumour-specific. To unravel molecular circuits linked to aberrant EGFR signalling diverse computational approaches were employed and this defined n = 7 key nodes using n = 82 disease regulated proteins for network construction. STRING analysis revealed protein-protein interactions of > 70% disease regulated proteins with individual proteins being validated by immunohistochemistry. The disease regulated network proteins were mapped to distinct pathways and bioinformatics provided novel insight into molecular circuits associated with significant changes in either glycolysis and gluconeogenesis, argine and proline metabolism, protein processing in endoplasmic reticulum, Hif- and MAPK signalling, lipoprotein metabolism, platelet activation and hemostatic control as a result of aberrant EGF signalling. The biological significance of the findings was corroborated with gene expression data derived from tumour tissues to evntually define a rationale by which tumours embark on intriguing changes in metabolism that is of utility for an understanding of tumour growth. Moreover, among the EGF tumour specific proteins n = 11 were likewise uniquely expressed in human HCC and for n = 49 proteins regulation in human HCC was confirmed using the publically available Human Protein Atlas depository, therefore demonstrating clinical significance. CONCLUSION: Novel insight into the molecular pathogenesis of EGF induced liver cancer was obtained and among the 37 newly identified proteins several are likely candidates for the development of molecularly targeted therapies and include the nucleoside diphosphate kinase A, bifunctional ATP-dependent dihydroyacetone kinase and phosphatidylethanolamine-binding protein1, the latter being an inhibitor of the Raf-1 kinase. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1312-z) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357185/ doi: 10.1186/s12864-015-1312-z id: cord-325943-3hvy7b7c author: Bouwman, Kim M. title: Guinea Fowl Coronavirus Diversity Has Phenotypic Consequences for Glycan and Tissue Binding date: 2019-05-01 words: 4810.0 sentences: 265.0 pages: flesch: 51.0 cache: ./cache/cord-325943-3hvy7b7c.txt txt: ./txt/cord-325943-3hvy7b7c.txt summary: Glycan array analysis revealed that, in addition to the previously elucidated biantennary di-N-acetyllactosamine (diLacNAc) receptor, viral attachment S1 proteins from GfCoV/2014 and GfCoV/2011 can bind to glycans capped with alpha-2,6-linked sialic acids. Our data indicate that diversity in GfCoV viral attachment proteins results in differences in degrees of affinity for glycan receptors, as well as altered avidity for intestinal tract tissues, which might have consequences for GfCoV tissue tropism and pathogenesis in guinea fowls. Glycan and tissue binding analyses of GfCoV/2011 and GfCoV/2014 recombinant spike S1 proteins revealed that while both proteins had the same specificities, GfCoV/2014 S1 had a much higher affinity toward glycan receptors and tissues of the lower gastrointestinal tract, in agreement with the observed replication of the virus in these tissues from field cases. abstract: Guinea fowl coronavirus (GfCoV) causes fulminating enteritis that can result in a daily death rate of 20% in guinea fowl flocks. Here, we studied GfCoV diversity and evaluated its phenotypic consequences. Over the period of 2014 to 2016, affected guinea fowl flocks were sampled in France, and avian coronavirus presence was confirmed by PCR on intestinal content and immunohistochemistry of intestinal tissue. Sequencing revealed 89% amino acid identity between the viral attachment protein S1 of GfCoV/2014 and that of the previously identified GfCoV/2011. To study the receptor interactions as a determinant for tropism and pathogenicity, recombinant S1 proteins were produced and analyzed by glycan and tissue arrays. Glycan array analysis revealed that, in addition to the previously elucidated biantennary di-N-acetyllactosamine (diLacNAc) receptor, viral attachment S1 proteins from GfCoV/2014 and GfCoV/2011 can bind to glycans capped with alpha-2,6-linked sialic acids. Interestingly, recombinant GfCoV/2014 S1 has an increased affinity for these glycans compared to that of GfCoV/2011 S1, which was in agreement with the increased avidity of GfCoV/2014 S1 for gastrointestinal tract tissues. Enzymatic removal of receptors from tissues before application of spike proteins confirmed the specificity of S1 tissue binding. Overall, we demonstrate that diversity in GfCoV S1 proteins results in differences in glycan and tissue binding properties. IMPORTANCE Avian coronaviruses cause major global problems in the poultry industry. As causative agents of huge economic losses, the detection and understanding of the molecular determinants of viral tropism are of ultimate importance. Here, we set out to study those parameters and obtained in-depth insight into the virus-host interactions of guinea fowl coronavirus (GfCoV). Our data indicate that diversity in GfCoV viral attachment proteins results in differences in degrees of affinity for glycan receptors, as well as altered avidity for intestinal tract tissues, which might have consequences for GfCoV tissue tropism and pathogenesis in guinea fowls. url: https://doi.org/10.1128/jvi.00067-19 doi: 10.1128/jvi.00067-19 id: cord-017866-h5ttoo0z author: Bowman, Grant R. title: Biogenesis of Dense-Core Secretory Granules date: 2010-05-27 words: 13369.0 sentences: 678.0 pages: flesch: 42.0 cache: ./cache/cord-017866-h5ttoo0z.txt txt: ./txt/cord-017866-h5ttoo0z.txt summary: For such regulated exocytosis, the vesicles that carry newly-synthesized protein from the TGN accumulate in the cytoplasm until specific extracellular events trigger their fusion with the plasma membrane, resulting in the release of vesicle contents.f The vesicles involved are called dense-core granules (DCGs), the name reflecting the fact that the contents are so highly condensed that they form a large electron-dense plug in the vesicle lumen. In support of this hypothesis, recent studies have suggested that prohormone convertases 1 and 2, which are responsible for proteolytic cleavageof lumenal proteins during granule maturation, are sorted to ISGs by virtue of C-terminal membrane raft-associated tails, which are by themselves necessary and sufficient for targeting to DCGs,uo 120 Additionally, cytoplasmic signals on some transmembrane proteins appear to play important roles in sorting, but the mechanisms are unknown. abstract: Dense core granules (DCGs) are vesicular organelles derived from outbound traffic through the eukaryotic secretory pathway. As DCGs are formed, the secretory pathway can also give rise to other types of vesicles, such as those bound for endosomes, lysosomes, and the cell surface. DCGs differ from these other vesicular carriers in both content and function, storing highly concentrated cores’ of condensed cargo in vesicles that are stably maintained within the cell until a specific extracellular stimulus causes their fusion with the plasma membrane. These unique features are imparted by the activities of membrane and lumenal proteins that are specifically delivered to the vesicles during synthesis. This chapter will describe the DCG biogenesis pathway, beginning with the sorting of DCG proteins from proteins that are destined for other types of vesicle carriers. In the trans-Golgi network (TGN), sorting occurs as DCG proteins aggregate, causing physical separation from non-DCG proteins. Recent work addresses the nature of interactions that produce these aggregates, as well as potentially important interactions with membranes and membrane proteins. DCG proteins are released from the TGN in vesicles called immature secretory granules (ISGs). The mechanism of ISG formation is largely unclear but is not believed to rely on the assembly of vesicle coats like those observed in other secretory pathways. The required cytosolic factors are now beginning to be identified using in vitro systems with purified cellular components. ISG transformation into a mature fusion-competent, stimulus-dependent DCG occurs as endoproteolytic processing of many DCG proteins causes continued condensation of the lumenal contents. At the same time, proteins that fail to be incorporated into the condensing core are removed by a coat-mediated budding mechanism, which also serves to remove excess membrane and membrane proteins from the maturing vesicle. This chapter will summarize the work leading to our current view of granule synthesis, and will discuss questions that need to be addressed in order to gain a more complete understanding of the pathway. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122546/ doi: 10.1007/978-0-387-93877-6_10 id: cord-003817-k3m72uxw author: Braun, Elisabeth title: Furin‐mediated protein processing in infectious diseases and cancer date: 2019-08-05 words: 9070.0 sentences: 557.0 pages: flesch: 41.0 cache: ./cache/cord-003817-k3m72uxw.txt txt: ./txt/cord-003817-k3m72uxw.txt summary: For example, avirulent Newcastle disease virus (NDV) strains harbour a monobasic cleavage site in their Fusion (F) protein and result only in local infections (mainly in the respiratory tract) since expression of the respective host proteases is limited to a few cell types. Notably, proteolytic processing of Env depends on correct N-linked glycosylation as aberrant carbohydrate side chains may result in subcellular mistrafficking or sequestration of Env. 49 Most likely, HIV-1 takes advantage of the redundancy of several proprotein convertases recognising the polybasic cleavage motif in Env. Furin, PCSK5, PCSK6 and PCSK7 have all been shown to cleave gp160 in cells, albeit with different efficiencies. 59, 60 Notably, a subset of H9N2 lowly pathogenic avian influenza A virus strains also harbour R-S-K-R↓ or R-S-R-R↓ sites that are not only cleaved by trypsin-like proteases, such as TMPRSS2 or HAT, but also by PCSKs. 61 However, their cleavage is only efficient in the presence of very high amounts of furin or upon mutation of a glycosylation site in HA. abstract: Proteolytic cleavage regulates numerous processes in health and disease. One key player is the ubiquitously expressed serine protease furin, which cleaves a plethora of proteins at polybasic recognition motifs. Mammalian substrates of furin include cytokines, hormones, growth factors and receptors. Thus, it is not surprising that aberrant furin activity is associated with a variety of disorders including cancer. Furthermore, the enzymatic activity of furin is exploited by numerous viral and bacterial pathogens, thereby enhancing their virulence and spread. In this review, we describe the physiological and pathophysiological substrates of furin and discuss how dysregulation of a simple proteolytic cleavage event may promote infectious diseases and cancer. One major focus is the role of furin in viral glycoprotein maturation and pathogenicity. We also outline cellular mechanisms regulating the expression and activation of furin and summarise current approaches that target this protease for therapeutic intervention. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682551/ doi: 10.1002/cti2.1073 id: cord-136540-2h2braww author: Buehler, Markus J. title: Liquified protein vibrations, classification and cross-paradigm de novo image generation using deep neural networks date: 2020-04-16 words: 3684.0 sentences: 209.0 pages: flesch: 51.0 cache: ./cache/cord-136540-2h2braww.txt txt: ./txt/cord-136540-2h2braww.txt summary: Here we present a method to transform these molecular vibrations into materialized vibrations of thin water films using acoustic actuators, leading to complex patterns of surface waves, and using the resulting macroscopic images in further processing using deep convolutional neural networks. Specifically, the patterns of water surface waves for each protein structure is used to build training sets for neural networks, aimed to classify and further process the patterns. Once trained, the neural network model is capable of discerning different proteins solely by analyzing the macroscopic surface wave patterns in the water film. This article focuses on a different perspective and reports a distinct, complementary and translational approach, in which we transform these molecular vibrations into vibrations of thin water films using acoustic actuators, leading to visual images of complex materialized patterns of surface waves. We use DeepDream [39] to generate novel images by activating select layers in the deep neural network, based on the model trained against the water surface images. abstract: In recent work we reported the vibrational spectrum of more than 100,000 known protein structures, and a self-consistent sonification method to render the spectrum in the audible range of frequencies (Extreme Mechanics Letters, 2019). Here we present a method to transform these molecular vibrations into materialized vibrations of thin water films using acoustic actuators, leading to complex patterns of surface waves, and using the resulting macroscopic images in further processing using deep convolutional neural networks. Specifically, the patterns of water surface waves for each protein structure is used to build training sets for neural networks, aimed to classify and further process the patterns. Once trained, the neural network model is capable of discerning different proteins solely by analyzing the macroscopic surface wave patterns in the water film. Not only can the method distinguish different types of proteins (e.g. alpha-helix vs hybrids of alpha-helices and beta-sheets), but it is also capable of determining different folding states of the same protein, or the binding events of proteins to ligands. Using the DeepDream algorithm, instances of key features of the deep neural network can be made visible in a range of images, allowing us to explore the inner workings of protein surface wave patter neural networks, as well as the creation of new images by finding and highlighting features of protein molecular spectra in a range of photographic input. The integration of the water-focused realization of cymatics, combined with neural networks and especially generative methods, offer a new direction to realize materiomusical"Inceptionism"as a possible direction in nano-inspired art. The method could have applications for detecting different protein structures, the effect of mutations, or uses in medical imaging and diagnostics, with broad impact in nano-to-macro transitions. url: https://arxiv.org/pdf/2004.07603v1.pdf doi: nan id: cord-171099-d0qr84xg author: Buehler, Markus J. title: Nanomechanical sonification of the 2019-nCoV coronavirus spike protein through a materiomusical approach date: 2020-03-30 words: 4509.0 sentences: 205.0 pages: flesch: 46.0 cache: ./cache/cord-171099-d0qr84xg.txt txt: ./txt/cord-171099-d0qr84xg.txt summary: Presenting musical encoding in two versions one in the amino-acid scale and one based on equal temperament tuning the method allows for expressing protein structures in audible space, offering novel avenues to represent, analyze and design architectural features across lengthand time-scales. We further report a hierarchical frequency spectrum analysis of five distinct protein structures, which offer insights into how genetic mutations, and the binding of the virus spike protein to the human ACE2 cell receptor directly influence the audio. What you hear is a multi-layered algorithmic composition featuring both the vibrational spectrum of the entire protein (expressed in sound and rhythmic elements), the sequence and folding of amino acids that compose the virus spike structure, as well as interwoven melodiesforming counterpoint music -reflecting the complex hierarchical intersecting geometry of the protein. abstract: Proteins are key building blocks of virtually all life, providing the material foundation of spider silk, cells, and hair, but also offering other functions from enzymes to drugs, and pathogens like viruses. Based on a nanomechanical analysis of the structure and motions of atoms and molecules at multiple scales, we report sonified versions of the coronavirus spike protein of the pathogen of COVID-19, 2019-nCoV. The audio signal, created using a novel nanomechanical sonification method, features an overlay of the vibrational signatures of the protein's primary, secondary and higher-order structures. Presenting musical encoding in two versions - one in the amino-acid scale and one based on equal temperament tuning - the method allows for expressing protein structures in audible space, offering novel avenues to represent, analyze and design architectural features across length- and time-scales. We further report a hierarchical frequency spectrum analysis of five distinct protein structures, which offer insights into how genetic mutations, and the binding of the virus spike protein to the human ACE2 cell receptor directly influence the audio. Applications of the approach may include the development of de novo antibodies by designing protein sequences that match, through melodic counterpoints, the binding sites in the spike protein. Other applications of audible coding of matter include material design by manipulating sound, detecting mutations, and offering a way to reach out to broader communities to explain the physics of proteins. It also forms a physics-based compositional technique to create new art, referred to as materiomusic, which is akin to finding a new palette of colors for a painter. Here, the nanomechanical structure of matter, reflected in an oscillatory framework, presents a new palette for sound generation, and can complement or support human creativity. url: https://arxiv.org/pdf/2003.14258v1.pdf doi: nan id: cord-266147-s8rxzm0t author: Burnouf, Thierry title: Modern Plasma Fractionation date: 2007-03-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Protein products fractionated from human plasma are an essential class of therapeutics used, often as the only available option, in the prevention, management, and treatment of life-threatening conditions resulting from trauma, congenital deficiencies, immunologic disorders, or infections. Modern plasma product production technology remains largely based on the ethanol fractionation process, but much has evolved in the last few years to improve product purity, to enhance the recovery of immunoglobulin G, and to isolate new plasma proteins, such as α1-protease inhibitor, von Willebrand factor, and protein C. Because of the human origin of the starting material and the pooling of 10 000 to 50 000 donations required for industrial processing, the major risk associated to plasma products is the transmission of blood-borne infectious agents. A complete set of measures—and, most particularly, the use of dedicated viral inactivation and removal treatments—has been implemented throughout the production chain of fractionated plasma products over the last 20 years to ensure optimal safety, in particular, and not exclusively, against HIV, hepatitis B virus, and hepatitis C virus. In this review, we summarize the practices of the modern plasma fractionation industry from the collection of the raw plasma material to the industrial manufacture of fractionated products. We describe the quality requirements of plasma for fractionation and the various treatments applied for the inactivation and removal of blood-borne infectious agents and provide examples of methods used for the purification of the various classes of plasma protein therapies. We also highlight aspects of the good manufacturing practices and the regulatory environment that govern the whole chain of production. In a regulated and professional environment, fractionated plasma products manufactured by modern processes are certainly among the lowest-risk therapeutic biological products in use today. url: https://www.sciencedirect.com/science/article/pii/S0887796306000940 doi: 10.1016/j.tmrv.2006.11.001 id: cord-355913-fhvt1ht1 author: Burrell, Christopher J. title: Virus Replication date: 2016-11-11 words: 9861.0 sentences: 405.0 pages: flesch: 42.0 cache: ./cache/cord-355913-fhvt1ht1.txt txt: ./txt/cord-355913-fhvt1ht1.txt summary: Little is known about what determines whether a given picornavirus positive-sense RNA molecule will be directed (1) to a replication complex (a structure bound to smooth endoplasmic reticulum), where it serves as template for transcription by RNA-dependent RNA polymerase into negative-sense RNA, or (2) to a ribosome, where it serves as mRNA for translation into protein, or (3) to a procapsid, with which it associates to form a virion. In the case of positive-sense single-stranded RNA viruses, the incoming RNA genome can bind directly to ribosomes and be translated in full or in part without the need for any prior transcription; all other forms of incoming viral RNA must first be transcribed to produce mRNA, in order to begin the process of expression of the infecting viral genome. abstract: Understanding the molecular events accompanying virus replication is essential for the proper understanding and control of all virus diseases. The virus replication cycle generates new viral genomes and proteins in sufficient quantities to ensure propagation of the viral genome; this requires that the extracellular viral genome is protected from enzymatic degradation and can be introduced into further target cells for further rounds of replication. The initial recognition between virus and host is more complex than originally supposed and may involve more than one cellular receptor. A critical first intracellular step is the generation of viral mRNA by one of a limited number of strategies first described by David Baltimore. Lacking ribosomes, viruses have no means of producing protein and are reliant on the host cell for protein synthesis. Viral proteins are often modified by host cell glycosylation during or after virus assembly. Temporal regulation of intracellular events is critical in all but the very simplest of viruses, and some form of suppression of the host innate immune response is common to nearly all human viruses. Infected cells often produce non-infectious particles with incomplete genomes, and these defective interfering particles may play a role in pathogenesis. Understanding these processes will open up a range of targets for the development of novel therapies. url: https://api.elsevier.com/content/article/pii/B9780123751560000047 doi: 10.1016/b978-0-12-375156-0.00004-7 id: cord-018647-bveks6t1 author: Butnariu, Monica title: Plant Nanobionics: Application of Nanobiosensors in Plant Biology date: 2019-10-01 words: 16812.0 sentences: 779.0 pages: flesch: 40.0 cache: ./cache/cord-018647-bveks6t1.txt txt: ./txt/cord-018647-bveks6t1.txt summary: Chemical or biological NBS functions on the principle of signal emission (voltage or electrical, photonic) in response to a chemical reaction involve a chemical or biological receptor, R (macrocyclic ligand, antibody enzyme), that binds to a specific target molecule of a sample to be studied, the analyte, A. Analysis of signals in plant nanobionics aims at processing signals recorded by measurements in order to extract the maximum of useful information for diagnostics and These devices are mostly used in genetic engineering in agriculture, where it is necessary to know the mechanisms of reaction and the affinity of enzymes and microorganisms for different substrates of interest and signaling molecules. The reaction is monitored by an integrated detector (transducer) that measures the stationary or transition states or the final reaction product via the immobilized biocidal product in NBSs. Types of commonly used biocatalysts are enzymes (simple or enzymatic complexes)-most commonly used as recognition systems, cells, microorganisms (bacteria, fungi, eukaryotic cells, or yeasts), cellular organs, or component (cell walls, mitochondria) sections of plant or animal tissues. abstract: Nanobiosensors (NBSs) are a class of chemical sensors which are sensitive to a physical or chemical stimulus (heat, acidity, metabolism transformations) that conveys information about vital processes. NBSs detect physiological signals and convert them into standardized signals, often electrical, to be quantified from analog to digital. NBSs are classified according to the transducer element (electrochemical, piezoelectric, optical, and thermal) in accordance with biorecognition principle (enzyme recognition, affinity immunoassay, whole sensors, DNA). NBSs have varied forms, depending on the degree of interpretation of natural processes in plants. Plant nanobionics uses mathematical models based on qualitative and less quantitative records. NBSs can give information about endogenous concentrations or endogenous fluxes of signaling molecules (phytohormones). The properties of NBSs are temporal and spatial resolution, the ability of being used without significantly interfering with the system. NBSs with the best properties are the optically genetically coded NBSs, but each NBS needs specific development efforts. NBS technologies using antibodies as a recognition domain are generic and tend to be more invasive, and there are examples of their use in plant nanobionics. Through opportunities that develop along with technologies, we hope that more and more NBSs will become available for plant nanobionics. The main advantages of NBSs are short analysis time, low-cost tests and portability, real-time measurements, and remote control. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123577/ doi: 10.1007/978-3-030-16379-2_12 id: cord-333309-21czobqy author: Byun, Hyewon title: ERAD and how viruses exploit it date: 2014-07-03 words: 11735.0 sentences: 630.0 pages: flesch: 45.0 cache: ./cache/cord-333309-21czobqy.txt txt: ./txt/cord-333309-21czobqy.txt summary: Interaction of lectin-type and other chaperones with ERAD substrates allows association with members of the protein disulfide isomerase (PDI) family, which generally are characterized by one or more thioredoxin-like motifs (CXXC; Brodsky and Skach, 2011) . In contrast to the rhomboid proteases, the Derlins lack proteolytic activity, suggesting that these proteins bind to ERAD substrates and target them to E3 ligases for ubiquitination and to p97 for membrane extraction (Brodsky, 2012) . These ubiquitin ligases are members of the cytosolic SCF (S-phase kinase-associated protein 1 (Skp1)-Cullin 1 (Cul1)-F-box) family, where the F-box components of the SCF complex recognize the N-glycans of the retrotranslocated substrate, e.g., Fbs1 and Fbs2 (Yoshida, 2007) . A proteasomal ATPase contributes to dislocation of endoplasmic reticulum-associated degradation (ERAD) substrates The viral E3 ubiquitin ligase mK3 uses the Derlin/p97 endoplasmic reticulum-associated degradation pathway to mediate down-regulation of major histocompatibility complex class I proteins abstract: Endoplasmic reticulum (ER)-associated degradation (ERAD) is a universally important process among eukaryotic cells. ERAD is necessary to preserve cell integrity since the accumulation of defective proteins results in diseases associated with neurological dysfunction, cancer, and infections. This process involves recognition of misfolded or misassembled proteins that have been translated in association with ER membranes. Recognition of ERAD substrates leads to their extraction through the ER membrane (retrotranslocation or dislocation), ubiquitination, and destruction by cytosolic proteasomes. This review focuses on ERAD and its components as well as how viruses use this process to promote their replication and to avoid the immune response. url: https://www.ncbi.nlm.nih.gov/pubmed/25071743/ doi: 10.3389/fmicb.2014.00330 id: cord-297960-4x1j0iqg author: Bösl, Korbinian title: Common Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis date: 2019-10-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape. url: https://doi.org/10.3389/fimmu.2019.02186 doi: 10.3389/fimmu.2019.02186 id: cord-339333-7tpnbr8q author: CHEN, YUXIAN title: Comparative serum proteome expression of the steroid-induced femoral head osteonecrosis in adults date: 2014-11-12 words: 3615.0 sentences: 211.0 pages: flesch: 47.0 cache: ./cache/cord-339333-7tpnbr8q.txt txt: ./txt/cord-339333-7tpnbr8q.txt summary: The differentially-expressed protein spots were subjected to in-gel trypsin digestion followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The purpose of the present study is to find potential biomarkers of the SONFH by using proteomic technology to analyze serum protein profiles in patients with SONFH and the healthy control group. To ensure the reproducibility, accuracy and objectivity of the experiments, the following steps were Differentially-expressed protein spots were identified from the two-dimensional difference gel electrophoresis profiling of human plasma, with a lower abundance in the steroid-induced femoral head osteonecrosis group compared to the control group. In the present study, four proteins (C3, C4, ITIH4 and A2MG) showed lower expression in the serum of patients with SONFH than that of the normal subjects. The present study shows that the expression of C3, C4, ITIH4 and A2MG were significantly altered in patients with SONFH. abstract: Steroid-induced osteonecrosis of the femoral head (SONFH) is a disabling, aseptic and ischemic disease that develops following steroid therapy. The pathogenesis of SONFH is unclear, so the early diagnosis and treatment for this disease is yet to be established. The purpose of the present study was to identify potential biomarkers for SONFH. The differential expression of serum proteins from patients with SONFH and healthy volunteers was analyzed by the proteomics method. The protein samples were labeled and subjected to isoelectric focusing and two-dimensional gel electrophoresis. The resultant protein spots were matched and quantified by an imaging analysis system. The differentially-expressed protein spots were subjected to in-gel trypsin digestion followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Significantly lower levels of complement component 3 (C3), C4, inter-α-trypsin inhibitor heavy chain H4 and α-2-macroglobulin were found in the serum of patients with SONFH. These proteins are reported to be actively involved in intravascular coagulation, apoptosis and reactive oxygen species imbalance, indicating that multiple pathological reactions occur in SONFH and these proteins may serve as potential biomarkers for the diagnosis of SONFH. url: https://www.ncbi.nlm.nih.gov/pubmed/25452779/ doi: 10.3892/etm.2014.2069 id: cord-286219-qcx5ehnh author: Calistri, Arianna title: The Ubiquitin-Conjugating System: Multiple Roles in Viral Replication and Infection date: 2014-05-06 words: 10182.0 sentences: 498.0 pages: flesch: 41.0 cache: ./cache/cord-286219-qcx5ehnh.txt txt: ./txt/cord-286219-qcx5ehnh.txt summary: In this review we will present several examples of the complex interplay that links viruses and the ubiquitin conjugation machinery, with a special focus on the mechanisms evolved by the human immunodeficiency virus to escape from cellular restriction factors and to exit from infected cells. Furthermore, small DNA viruses with known oncogenic activity, such as the human papillomavirus (HPV), adenoviruses and polyomaviruses, take control of the cell cycle by usurping specific cellular Ub ligase complexes to target crucial cell cycle regulators such as p53 and the protein of the retinoblastoma (pRB) for degradation [58] . In addition to this important function, which is likely required for proper trafficking and maturation of the viral envelope glycoproteins, Vpu has been more recently characterized for yet another crucial role, connected with the ability of the virus to evade a specific IFN-1 induced antiviral factor: the B cell stromal factor 2 (BST-2) or tetherin. abstract: Through the combined action of ubiquitinating and deubiquitinating enzymes, conjugation of ubiquitin to a target protein acts as a reversible post-translational modification functionally similar to phosphorylation. Indeed, ubiquitination is more and more recognized as a central process for the fine regulation of many cellular pathways. Due to their nature as obligate intracellular parasites, viruses rely on the most conserved host cell machineries for their own replication. Thus, it is not surprising that members from almost every viral family are challenged by ubiquitin mediated mechanisms in different steps of their life cycle and have evolved in order to by-pass or exploit the cellular ubiquitin conjugating system to maximize their chance to establish a successful infection. In this review we will present several examples of the complex interplay that links viruses and the ubiquitin conjugation machinery, with a special focus on the mechanisms evolved by the human immunodeficiency virus to escape from cellular restriction factors and to exit from infected cells. url: https://doi.org/10.3390/cells3020386 doi: 10.3390/cells3020386 id: cord-314642-oobbdgzh author: Campbell, Allan title: The future of bacteriophage biology date: 2003 words: 5945.0 sentences: 308.0 pages: flesch: 53.0 cache: ./cache/cord-314642-oobbdgzh.txt txt: ./txt/cord-314642-oobbdgzh.txt summary: Several molecules of λ-integrase form an assemblage (the INTASOME) that binds to a specific segment of phage DNA, recruits the bacterial insertion sites into the complex, then makes concerted single-strand cuts in the two DNAs. The strand cutting proceeds through the covalent joining of a 3′ phosphate to a tyrosine of the integrase protein. Further efforts in this direction are desirable, not just for their intrinsic interest but also as models for viruses that infect eukaryotic hosts; for example, it is well documented that members of the coronavirus group, which has attracted attention recently through the emergence of a deadly new human pathogen that causes severe acute respiratory syndrome (SARS), undergo frequent recombination in nature 10, 11 . abstract: After an illustrious history as one of the primary tools that established the foundations of molecular biology, bacteriophage research is now undergoing a renaissance in which the primary focus is on the phages themselves rather than the molecular mechanisms that they explain. Studies of the evolution of phages and their role in natural ecosystems are flourishing. Practical questions, such as how to use phages to combat human diseases that are caused by bacteria, how to eradicate phage pests in the food industry and what role they have in the causation of human diseases, are receiving increased attention. Phages are also useful in the deeper exploration of basic molecular and biophysical questions. url: https://www.ncbi.nlm.nih.gov/pubmed/12776216/ doi: 10.1038/nrg1089 id: cord-272986-ebgusf3o author: Cao, Yipeng title: Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel date: 2020-05-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus (SARS-CoV-2) and represents the causative agent of a potentially fatal disease that is of public health emergency of international concern. Coronaviruses, including SARS-CoV-2, encode an envelope (E) protein, which is a small, hydrophobic membrane protein; the E protein of SARS-CoV-2 has high homology with that of severe acute respiratory syndrome coronavirus. (SARS-CoV) In this study, we provide insights into the function of the SARS-CoV-2 E protein channel and the ion and water permeation mechanisms on the basis of combined in silico methods. Our results suggest that the pentameric E protein promotes the penetration of monovalent ions through the channel. Analysis of the potential mean force (PMF), pore radius and diffusion coefficient reveals that Leu10 and Phe19 are the hydrophobic gates of the channel. In addition, the pore demonstrated a clear wetting/dewetting transition with monovalent cation selectivity under transmembrane voltage, which indicates that it is a hydrophobic voltage-dependent channel. Overall, these results provide structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SARS-CoV-2 E protein channel. url: https://doi.org/10.1101/2020.05.17.099143 doi: 10.1101/2020.05.17.099143 id: cord-325559-di8lljoi author: Cappello, Francesco title: Does SARS-CoV-2 Trigger Stress-Induced Autoimmunity by Molecular Mimicry? A Hypothesis date: 2020-06-29 words: 5204.0 sentences: 298.0 pages: flesch: 44.0 cache: ./cache/cord-325559-di8lljoi.txt txt: ./txt/cord-325559-di8lljoi.txt summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced disease (COVID-19) is a planetary emergency that is urging many research groups to redirect their efforts and to channel their experience towards understanding its pathogenesis. These human epitopes, in turn, can be recognized by circulating antibodies made against crossreactive microbial antigens; these antibodies behave like autoantibodies, causing the destruction of the stressed cells, representing a typical example of pathology caused by molecular mimicry and manifested as autoimmunity [30] . We hypothesize that, at the basis of the generalized activation of the immune system, there are molecular mimicry phenomena: the antibodies produced against the virus could turn into autoantibodies against crossreactive proteins expressed on human cells, causing autoimmunity with cell destruction. We hypothesize that, at the basis of the generalized activation of the immune system, there are molecular mimicry phenomena: the antibodies produced against the virus could turn into autoantibodies against crossreactive proteins expressed on human cells, causing autoimmunity with cell destruction. abstract: Viruses can generate molecular mimicry phenomena within their hosts. Why should severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these? Information in this short review suggests that it might be so and, thus, encourages research aiming at testing this possibility. We propose, as a working hypothesis, that the virus induces antibodies and that some of them crossreact with host’s antigens, thus eliciting autoimmune phenomena with devasting consequences in various tissues and organs. If confirmed, by in vitro and in vivo tests, this could drive researchers to find effective treatments against the virus. url: https://doi.org/10.3390/jcm9072038 doi: 10.3390/jcm9072038 id: cord-000372-wzwpyvll author: Castelló, Alfredo title: The Multifaceted Poliovirus 2A Protease: Regulation of Gene Expression by Picornavirus Proteases date: 2011-04-14 words: 16333.0 sentences: 781.0 pages: flesch: 45.0 cache: ./cache/cord-000372-wzwpyvll.txt txt: ./txt/cord-000372-wzwpyvll.txt summary: These findings are in agreement with the fact that host mRNA transcription takes place in 2A pro -expressing cells when both translation and RNA nuclear export are inhibited, upon cleavage of eIF4G and Nups [17] . In this regard, PV 2A pro has been very useful for examining the requirements for eIF4G to translate different cellular or viral mRNAs. In addition to this, in this paper, we have highlighted the role of PV 2A pro not only in the processing of the poliovirus polyprotein but also in the interaction with the host-cell. In particular, PV 2A pro cleaves cell proteins involved in transcription, pre-mRNA splicing, nucleus/cytoplasm transport and translation, in order to hijack those host functions and to concentrate the cellular resources on the production of the viral progeny. abstract: After entry into animal cells, most viruses hijack essential components involved in gene expression. This is the case of poliovirus, which abrogates cellular translation soon after virus internalization. Abrogation is achieved by cleavage of both eIF4GI and eIF4GII by the viral protease 2A. Apart from the interference of poliovirus with cellular protein synthesis, other gene expression steps such as RNA and protein trafficking between nucleus and cytoplasm are also altered. Poliovirus 2A(pro) is capable of hydrolyzing components of the nuclear pore, thus preventing an efficient antiviral response by the host cell. Here, we compare in detail poliovirus 2A(pro) with other viral proteins (from picornaviruses and unrelated families) as regard to their activity on key host factors that control gene expression. It is possible that future analyses to determine the cellular proteins targeted by 2A(pro) will uncover other cellular functions ablated by poliovirus infection. Further understanding of the cellular proteins hydrolyzed by 2A(pro) will add further insight into the molecular mechanism by which poliovirus and other viruses interact with the host cell. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085340/ doi: 10.1155/2011/369648 id: cord-302490-em1tiz7s author: Cañadas, Olga title: Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis date: 2020-05-25 words: 16675.0 sentences: 733.0 pages: flesch: 32.0 cache: ./cache/cord-302490-em1tiz7s.txt txt: ./txt/cord-302490-em1tiz7s.txt summary: To fulfill this crucial role, alveolar epithelial type II cells (AE2C) secrete pulmonary surfactant, a lipid-protein complex that forms a surface active film at the respiratory interface, allowing its stability and avoiding alveolar collapse during expiration [3, 4] . On the other hand, the structure of surfactant aggregates does not influence its uptake by AMs [169] , and although SP-D is able to bind to the surface of these cells to modulate inflammation, the homeostasis/immune roles of the protein seem to be independently regulated [94] . Surfactant proteins and lipids have been shown to provide immune protection against respiratory pathogens, both directly by limiting inflammation and promoting pathogen clearance, and indirectly by activating molecular and cellular mechanisms that contribute to restore lung homeostasis [15, [181] [182] [183] . Anionic pulmonary surfactant phospholipids inhibit inflammatory responses from alveolar macrophages and U937 cells by binding the lipopolysaccharide-interacting proteins CD14 and MD-2 abstract: Pulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface. url: https://www.ncbi.nlm.nih.gov/pubmed/32466119/ doi: 10.3390/ijms21103708 id: cord-275023-0z219rcy author: Cerofolini, Linda title: Orientation of immobilized antigens on common surfaces by a simple computational model: Exposition of SARS-CoV-2 Spike protein RBD epitopes date: 2020-07-29 words: 3485.0 sentences: 198.0 pages: flesch: 44.0 cache: ./cache/cord-275023-0z219rcy.txt txt: ./txt/cord-275023-0z219rcy.txt summary: title: Orientation of immobilized antigens on common surfaces by a simple computational model: Exposition of SARS-CoV-2 Spike protein RBD epitopes In this manuscript, we apply a simple computational model, based on united-residue modelling, to the prediction of the orientation of the receptor binding domain of the SARS-CoV-2 spike protein on surfaces commonly used in lateral-flow devices. In this manuscript we apply a very simple method based on a unitedresidue modelling of protein-surface interactions, to specifically address the problem of determining the orientation of the SARS-CoV-2 Spike protein Receptor Binding Domain (RBD) on a few prototypical surfaces for biomedical use. In this work, we describe the use of united-residue modelling for the prediction of the orientation of the receptor binding domain of the spike protein of the novel coronavirus SARS-CoV-2, a protein of high immunological relevance at the most commonly used surfaces for the preparation of lateral-flow immunochemical devices. abstract: The possibility of immobilizing a protein with antigenic properties on a solid support offers significant possibilities in the development of immunosensors and vaccine formulations. For both applications, the orientation of the antigen should ensure ready accessibility of the antibodies to the epitope. However, an experimental assessment of the orientational preferences necessarily proceeds through the preparation/isolation of the antigen, the immobilization on different surfaces and one or more biophysical characterization steps. To predict a priori whether favorable orientations can be achieved or not would allow one to select the most promising experimental routes, partly mitigating the time cost towards the final product. In this manuscript, we apply a simple computational model, based on united-residue modelling, to the prediction of the orientation of the receptor binding domain of the SARS-CoV-2 spike protein on surfaces commonly used in lateral-flow devices. These calculations can account for the experimental observation that direct immobilization on gold gives sufficient exposure of the epitope to obtain a response in immunochemical assays. url: https://doi.org/10.1016/j.bpc.2020.106441 doi: 10.1016/j.bpc.2020.106441 id: cord-324325-rmlrhyf2 author: Chan, Wai S title: Coronaviral hypothetical and structural proteins were found in the intestinal surface enterocytes and pneumocytes of severe acute respiratory syndrome (SARS) date: 2005-05-13 words: 3733.0 sentences: 225.0 pages: flesch: 43.0 cache: ./cache/cord-324325-rmlrhyf2.txt txt: ./txt/cord-324325-rmlrhyf2.txt summary: Immunohistochemical studies on different human tissues, including a cohort of nine autopsies, two liver biopsies and intestinal biopsies of SARS patients, further confirmed the existence of coronaviral hypothetical and structural proteins in the cytoplasm of pneumocytes and small intestinal surface enterocytes in SARS patients. In those tissue sections showing positive signals for immunohistochemical staining, we further performed immunohistochemical studies using all other antibodies tested positive in SARS-CoV-infected Vero E6 cells. The cellular distribution of SARS-CoV protein and viral genome in immunohistochemical-positive lung and small intestine sections was further evaluated by immunofluorescence-fluorescence in situ hybridization analysis (Figure 4) . 3 In Vero E6 cells, positive cytoplasmic immunohistochemical signals were detected by Figure 3 Immunohistochemical studies of antipeptide antibody SARS-AbS13a against the nucleocapsid protein on small intestine sections. In addition, in the study of tissue sections, only those cells with viral genome detected by fluorescence in situ hybridization were positive for immunohistochemical stainings for the antipeptide antibodies. abstract: Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease that haunted the world from November 2002 to July 2003. Little is known about the biology and pathophysiology of the novel coronavirus that causes SARS. The tissue and cellular distributions of coronaviral hypothetical and structural proteins in SARS were investigated. Antibodies against the hypothetical (SARS 3a, 3b, 6, 7a and 9b) and structural proteins (envelope, membrane, nucleocapsid and spike) of the coronavirus were generated from predicted antigenic epitopes of each protein. The presence of these proteins were first verified in coronavirus-infected Vero E6 tissue culture model. Immunohistochemical studies on different human tissues, including a cohort of nine autopsies, two liver biopsies and intestinal biopsies of SARS patients, further confirmed the existence of coronaviral hypothetical and structural proteins in the cytoplasm of pneumocytes and small intestinal surface enterocytes in SARS patients. With this vast array of antibodies, no signal was observed in other cell types including those organs in which reverse transcriptase-polymerase chain reactions were reported to be positive. Structural proteins and the functionally undefined hypothetical proteins were expressed in coronavirus-infected cells with distinct expression pattern in different organs in SARS patients. These antipeptide antibodies can be useful for the diagnosis of SARS at the tissue level. url: https://www.ncbi.nlm.nih.gov/pubmed/15920543/ doi: 10.1038/modpathol.3800439 id: cord-000264-o80duxhs author: Chandramouli, Kondethimmanahalli title: Proteomics: Challenges, Techniques and Possibilities to Overcome Biological Sample Complexity date: 2009-12-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Proteomics is the large-scale study of the structure and function of proteins in complex biological sample. Such an approach has the potential value to understand the complex nature of the organism. Current proteomic tools allow large-scale, high-throughput analyses for the detection, identification, and functional investigation of proteome. Advances in protein fractionation and labeling techniques have improved protein identification to include the least abundant proteins. In addition, proteomics has been complemented by the analysis of posttranslational modifications and techniques for the quantitative comparison of different proteomes. However, the major limitation of proteomic investigations remains the complexity of biological structures and physiological processes, rendering the path of exploration paved with various difficulties and pitfalls. The quantity of data that is acquired with new techniques places new challenges on data processing and analysis. This article provides a brief overview of currently available proteomic techniques and their applications, followed by detailed description of advantages and technical challenges. Some solutions to circumvent technical difficulties are proposed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950283/ doi: 10.4061/2009/239204 id: cord-279598-xzionafe author: Chang, Chia-Yu title: Identification of Neutralizing Monoclonal Antibodies Targeting Novel Conformational Epitopes of the Porcine Epidemic Diarrhoea Virus Spike Protein date: 2019-02-21 words: 5378.0 sentences: 267.0 pages: flesch: 53.0 cache: ./cache/cord-279598-xzionafe.txt txt: ./txt/cord-279598-xzionafe.txt summary: title: Identification of Neutralizing Monoclonal Antibodies Targeting Novel Conformational Epitopes of the Porcine Epidemic Diarrhoea Virus Spike Protein However, E10E-1-10, which targets a novel neutralizing epitope as shown with ICC staining, was also capable of binding to the full-length PEDV spike protein as well as truncated PEDV proteins, S 1-639 , S 1-575 , S 1-509 , S 1-501 , and S 1-485 with appropriate dilution effects. Similar to the results obtained by ICC staining, E10E-1-10 showed no binding ability www.nature.com/scientificreports www.nature.com/scientificreports/ toward PEDV S 1-435 by ELISA and therefore, an NmAb targeting a novel epitope of the new variant of PEDV specifically at a.a. 435-485 in the S1 region was confirmed. To further determine whether the binding of neutralizing epitopes require conformational integrity, immunodot blotting was performed by denaturing the various truncated PEDV spike proteins. Cell Attachment Domains of the Porcine Epidemic Diarrhea Virus Spike Protein Are Key Targets of Neutralizing Antibodies abstract: Since 2010, newly identified variants of porcine epidemic diarrhoea virus (PEDV) have caused high mortality in neonatal piglets which has devastated the swine industry. The spike (S) glycoprotein of PEDV contains multiple neutralizing epitopes and is a major target for PEDV neutralization and vaccine development. To understand the antigenicity of the new PEDV variant, we characterized the neutralizing epitopes of a new genotype 2b PEDV isolate from Taiwan, PEDV Pintung 52 (PEDV-PT), by the generation of neutralizing monoclonal antibodies (NmAbs). Two NmAbs, P4B-1, and E10E-1–10 that recognized the ectodomain of the full-length recombinant PEDV S protein and exhibited neutralizing ability against the PEDV-PT virus were selected. Recombinant truncated S proteins were used to identify the target sequences for the NmAbs and P4B-1 was shown to recognize the C-terminus of CO-26K equivalent epitope (COE) at amino acids (a.a.) 575–639 of the PEDV S. Interestingly, E10E-1–10 could recognize a novel neutralizing epitope at a.a. 435–485 within the S1(A) domain of the PEDV S protein, whose importance and function are yet to be determined. Moreover, both NmAbs could not bind to linearized S proteins, indicating that only conformational epitopes are recognized. This data could improve our understanding of the antigenic structures of the PEDV S protein and facilitate future development of novel epitope-based vaccines. url: https://doi.org/10.1038/s41598-019-39844-5 doi: 10.1038/s41598-019-39844-5 id: cord-342639-vf9n2vf9 author: Chang, Chung-ke title: Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging date: 2013-05-23 words: 5386.0 sentences: 243.0 pages: flesch: 42.0 cache: ./cache/cord-342639-vf9n2vf9.txt txt: ./txt/cord-342639-vf9n2vf9.txt summary: For disulfide trapping experiments, we chose mutation sites that would form disulfide linkages based on the crystal packing structures of the SARS-CoV N protein CTD ( Figure 1 ) [9] . Within the crystal asymmetric unit, the SARS-CoV N protein CTD packs as an octamer which stacks to form a helical arrangement with a continuous positively charged surface that could potentially allow the RNA to bind to it through electrostatic interactions ( Fig. 1 ) [9] . By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that SARS-CoV N protein is capable of transient oligomerization in solution through the CTD in the absence of nucleic acids. Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA abstract: The nucleocapsid (N) phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD). A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization. url: https://www.ncbi.nlm.nih.gov/pubmed/23717688/ doi: 10.1371/journal.pone.0065045 id: cord-337825-ujq9mxk7 author: Chen, Bin title: Overview of lethal human coronaviruses date: 2020-06-10 words: 13423.0 sentences: 761.0 pages: flesch: 51.0 cache: ./cache/cord-337825-ujq9mxk7.txt txt: ./txt/cord-337825-ujq9mxk7.txt summary: Coronaviruses are the largest +ssRNA viruses and contain at least 14 ORFs, 16 protein combines with viral RNA to form a nucleocapsid, which is involved in the replication of SARS-CoV and is the most abundant protein in virus-infected cells. MERS-CoV can infect T-cells from human lymphoid organs and causes the peripheral blood inducing apoptosis by intrinsic and extrinsic pathways, thus avoiding host immune response detection method, Nanopore Targeted Sequencing, also has the potential for efficiently detecting viruses in a reasonable time. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine abstract: Coronavirus infections of multiple origins have spread to date worldwide, causing severe respiratory diseases. Seven coronaviruses that infect humans have been identified: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. Among them, SARS-CoV and MERS-CoV caused outbreaks in 2002 and 2012, respectively. SARS-CoV-2 (COVID-19) is the most recently discovered. It has created a severe worldwide outbreak beginning in late 2019, leading to date to over 4 million cases globally. Viruses are genetically simple, yet highly diverse. However, the recent outbreaks of SARS-CoV and MERS-CoV, and the ongoing outbreak of SARS-CoV-2, indicate that there remains a long way to go to identify and develop specific therapeutic treatments. Only after gaining a better understanding of their pathogenic mechanisms can we minimize viral pandemics. This paper mainly focuses on SARS-CoV, MERS-CoV, and SARS-CoV-2. Here, recent studies are summarized and reviewed, with a focus on virus–host interactions, vaccine-based and drug-targeted therapies, and the development of new approaches for clinical diagnosis and treatment. url: https://doi.org/10.1038/s41392-020-0190-2 doi: 10.1038/s41392-020-0190-2 id: cord-330668-7aw17jf8 author: Chen, Cheng-Chang title: ORF8a of SARS-CoV forms an ion channel: Experiments and molecular dynamics simulations date: 2011-02-28 words: 4806.0 sentences: 274.0 pages: flesch: 56.0 cache: ./cache/cord-330668-7aw17jf8.txt txt: ./txt/cord-330668-7aw17jf8.txt summary: The protein is synthesized using solid phase peptide synthesis and reconstituted into artificial lipid bilayers that forms cation-selective ion channels with a main conductance level of 8.9±0.8pS at elevated temperature (38.5°C). Computational modeling studies including multi nanosecond molecular dynamics simulations in a hydrated POPC lipid bilayer are done with a 22 amino acid transmembrane helix to predict a putative homooligomeric helical bundle model. Before embedding low energy models into lipid bilayers two amino acids residues of the protein were added at the N and C termini of each of the helices in each bundle model to account for the consequences of their interaction with the lipid bilayer during the simulation. The idealized monomeric TM helix based on the consensus sequence Leu-3 to Val-20 (Fig. 1A) shows clustering of hydrophilic residues (Thr-8, Ser-11, Ser-14 and Thr-18) on one side suggesting that the four hydrophilic amino acids form the lumen of the pore in a homooligomeric helical bundle channel model. abstract: Abstract ORF8a protein is 39 residues long and contains a single transmembrane domain. The protein is synthesized using solid phase peptide synthesis and reconstituted into artificial lipid bilayers that forms cation-selective ion channels with a main conductance level of 8.9±0.8pS at elevated temperature (38.5°C). Computational modeling studies including multi nanosecond molecular dynamics simulations in a hydrated POPC lipid bilayer are done with a 22 amino acid transmembrane helix to predict a putative homooligomeric helical bundle model. A structural model of a pentameric bundle is proposed with cysteines, serines and threonines facing the pore. url: https://www.ncbi.nlm.nih.gov/pubmed/20708597/ doi: 10.1016/j.bbamem.2010.08.004 id: cord-335310-61wibso4 author: Chen, Hui-Wen title: Synthetic virus-like particles prepared via protein corona formation enable effective vaccination in an avian model of coronavirus infection date: 2016-08-15 words: 5482.0 sentences: 264.0 pages: flesch: 40.0 cache: ./cache/cord-335310-61wibso4.txt txt: ./txt/cord-335310-61wibso4.txt summary: Herein, a facile approach to formulate synthetic virus-like particles (sVLPs) is demonstrated by exploiting the phenomenon of protein corona formation induced by the high-energy surfaces of synthetic nanoparticles. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms in an avian model of coronavirus infection. Comparison to a commercial whole inactivated virus vaccine also showed evidence of superior antiviral protection by the sVLPs. The study demonstrates a simple yet robust method in bridging viral antigens with synthetic nanoparticles for improved vaccine application; it has practical implications in the management of human viral infections as well as in animal agriculture. In the present study, vaccination with the sVLPs resulted in enhanced humoral and cellular immune responses, improving protection against an avian model of coronavirus infection as compared to free protein antigens and a commercial WIV vaccine. abstract: The ongoing battle against current and rising viral infectious threats has prompted increasing effort in the development of vaccine technology. A major thrust in vaccine research focuses on developing formulations with virus-like features towards enhancing antigen presentation and immune processing. Herein, a facile approach to formulate synthetic virus-like particles (sVLPs) is demonstrated by exploiting the phenomenon of protein corona formation induced by the high-energy surfaces of synthetic nanoparticles. Using an avian coronavirus spike protein as a model antigen, sVLPs were prepared by incubating 100 nm gold nanoparticles in a solution containing an optimized concentration of viral proteins. Following removal of free proteins, antigen-laden particles were recovered and showed morphological semblance to natural viral particles under nanoparticle tracking analysis and transmission electron microscopy. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms in an avian model of coronavirus infection. Comparison to a commercial whole inactivated virus vaccine also showed evidence of superior antiviral protection by the sVLPs. The study demonstrates a simple yet robust method in bridging viral antigens with synthetic nanoparticles for improved vaccine application; it has practical implications in the management of human viral infections as well as in animal agriculture. url: https://doi.org/10.1016/j.biomaterials.2016.08.018 doi: 10.1016/j.biomaterials.2016.08.018 id: cord-011602-hzqayt3n author: Chen, Jianlin title: Targeting Intrinsically Disordered Proteins through Dynamic Interactions date: 2020-05-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Intrinsically disordered proteins (IDPs) are over-represented in major disease pathways and have attracted significant interest in understanding if and how they may be targeted using small molecules for therapeutic purposes. While most existing studies have focused on extending the traditional structure-centric drug design strategies and emphasized exploring pre-existing structure features of IDPs for specific binding, several examples have also emerged to suggest that small molecules could achieve specificity in binding IDPs and affect their function through dynamic and transient interactions. These dynamic interactions can modulate the disordered conformational ensemble and often lead to modest compaction to shield functionally important interaction sites. Much work remains to be done on further elucidation of the molecular basis of the dynamic small molecule–IDP interaction and determining how it can be exploited for targeting IDPs in practice. These efforts will rely critically on an integrated experimental and computational framework for disordered protein ensemble characterization. In particular, exciting advances have been made in recent years in enhanced sampling techniques, Graphic Processing Unit (GPU)-computing, and protein force field optimization, which have now allowed rigorous physics-based atomistic simulations to generate reliable structure ensembles for nontrivial IDPs of modest sizes. Such de novo atomistic simulations will play crucial roles in exploring the exciting opportunity of targeting IDPs through dynamic interactions. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277182/ doi: 10.3390/biom10050743 id: cord-313932-f0a1qh7p author: Chen, Peng title: Establishment and validation of a drug-target microarray for SARS-CoV-2 date: 2020-07-21 words: 2483.0 sentences: 148.0 pages: flesch: 49.0 cache: ./cache/cord-313932-f0a1qh7p.txt txt: ./txt/cord-313932-f0a1qh7p.txt summary: Here, we constructed a COVID-19 protein microarray of potential therapy targets, which contains the main drug targets to the SARS-COV-2 virus and the anti-virus, anti-inflammatory cellar targets of the host. For protein target research of traditional Chinese medicine, it is usually carried out through network pharmacology and bioinformatics, for example, by obtaining the main active ingredients of LianhuaQingwen capsule, molecular docking method was used to predict the possible targets [11, 12] . The latest research showed EIF4E2 as an important host interaction protein with virus, potential to be a drug target for COVID-19 [24] . NFkB1-P50 protein is an important target of andrographolide, a traditional Chinese medicine product with immunoregulation function, and their binding site has been widely verified [26] (Figure 3A ). Here, we use the method of network pharmacology molecular docking to predict the binding ability of these two natural products to the protein targets. abstract: COVID-19 has become one of the worst epidemic in the world, currently already more than four million people have been infected, which probably co-exist with human beings, and has a significant impact on the global economy and political order. In the process of fighting against the epidemic in China, the clinical value of a variety of herbal medicines has been recognized and written into the clinical application guide. However, their effective molecular mechanism and potential targets are still not clear. Pathology and pharmacology research will gradually attract attention in the post-epidemic outbreak term. Here, we constructed a COVID-19 protein microarray of potential therapy targets, which contains the main drug targets to the SARS-COV-2 virus and the anti-virus, anti-inflammatory cellar targets of the host. Series of quality controls test has been carried out, which showed that it could be applied for drug target screening of bio-active natural products. The establishment of this microarray will provide a useful tool for the study of the molecular pharmacology of natural products. url: https://doi.org/10.1016/j.bbrc.2020.05.217 doi: 10.1016/j.bbrc.2020.05.217 id: cord-314321-klb8oe9q author: Chen, Serena H. title: Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets date: 2020-04-18 words: 3168.0 sentences: 174.0 pages: flesch: 52.0 cache: ./cache/cord-314321-klb8oe9q.txt txt: ./txt/cord-314321-klb8oe9q.txt summary: Recent experimental structures of the SARS-CoV-2 S protein receptor binding domain (RBD) in complex with ACE2 provide detailed interface information [4] , [6] ; targeting this interface represents an active area of research for therapeutic development [11] . By first comparing the S protein protomer structure of SARS-CoV-2 to those from previous human coronaviruses, we identified distinct clusters for each virus in the 3-D latent space, where representative structures from these clusters highlight their differences in domain flexibility. To further understand the molecular structures of different human coronavirus S proteins and the oligomeric state of SARS-CoV-2 S protein, we deployed a custom-built deep learning architecture, a convolutional variational autoencoder (CVAE), to encode the high dimensional protein structures from the MD simulations into lower dimensional latent spaces. The size of each resulting matrix was also 191 ⇥ 191, and we merged a total of 10,000 distance matrices of the protomer and trimer of SARS-CoV-2 S protein. abstract: The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19. url: https://doi.org/10.1101/2020.04.17.047548 doi: 10.1101/2020.04.17.047548 id: cord-320015-lbr2q4qh author: Chinchar, V. Gregory title: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date: 2011-10-20 words: 9130.0 sentences: 433.0 pages: flesch: 43.0 cache: ./cache/cord-320015-lbr2q4qh.txt txt: ./txt/cord-320015-lbr2q4qh.txt summary: Additional IE and DE proteins include proteins that may play roles in blocking host immune responses such as a virus-encoded, CARD (caspase activation and recruitment domain) motif-containing protein (vCARD), β-hydroxysteroid dehydrogenase (βHSD), and a RNAse III-like protein, catalytic proteins involved in nucleic acid synthesis (Proliferating Cell Nuclear Antigen [PCNA], DNA methyltransferase [DMTase], the large and small subunits of the viral homolog of cellular RNA polymerase II [vPOL-IIα and -IIβ], transcription factor IIS), catalytic proteins that may act to increase dTTP pool sizes and influence host range (deoxyuridine triphosphatase [dUTPase], deoxynucleotide kinase, the large and small subunits of ribonucleotide reductase), and proteins non-essential for replication in vitro, but needed for growth in vivo (the 18K protein) [22] . Lastly, Sample and co-workers observed that KD of the 18K IE protein had no observable effect on viral gene expression or replication in vitro suggesting that, at least in fathead minnow cells, 18K was not required for the production of infectious virions. abstract: Frog virus 3 (FV3) is the best characterized member of the family Iridoviridae. FV3 study has provided insights into the replication of other family members, and has served as a model of viral transcription, genome replication, and virus-mediated host-shutoff. Although the broad outlines of FV3 replication have been elucidated, the precise roles of most viral proteins remain unknown. Current studies using knock down (KD) mediated by antisense morpholino oligonucleotides (asMO) and small, interfering RNAs (siRNA), knock out (KO) following replacement of the targeted gene with a selectable marker by homologous recombination, ectopic viral gene expression, and recombinant viral proteins have enabled researchers to systematically ascertain replicative- and virulence-related gene functions. In addition, the application of molecular tools to ecological studies is providing novel ways for field biologists to identify potential pathogens, quantify infections, and trace the evolution of ecologically important viral species. In this review, we summarize current studies using not only FV3, but also other iridoviruses infecting ectotherms. As described below, general principles ascertained using FV3 served as a model for the family, and studies utilizing other ranaviruses and megalocytiviruses have confirmed and extended our understanding of iridovirus replication. Collectively, these and future efforts will elucidate molecular events in viral replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease. url: https://doi.org/10.3390/v3101959 doi: 10.3390/v3101959 id: cord-014852-6friw2ek author: Chumakov, S. P. title: Organization and regulation of nucleocytoplasmic transport date: 2010-04-24 words: 9153.0 sentences: 496.0 pages: flesch: 50.0 cache: ./cache/cord-014852-6friw2ek.txt txt: ./txt/cord-014852-6friw2ek.txt summary: Nuclear RanGTP is capable of releasing the target protein from an imported complex upon binding with karyo pherins. The main properties that allow karyopherins to ensure efficient nuclear transport are their capabilities of binding with a target protein (directly or through an adaptor) and interacting with Nup or RanGTP [12] . Structural studies of karyopherin β1 in complex with the phenylalanine-glycine (FG) repeat contain ing fragment of yeast Nup showed that the interactions between the two proteins are mostly hydrophobic and involve the phenylalanine residues of Nup. The karyo pherin molecule forms two hydrophobic pockets: between HEAT repeats 5 and 6 and between repeats 6 and 7. NTF2 interacts with RanGDP, which is the main cytoplasmic form of Ran. The NTF2-RanGDP complex is transferred into the nucleus, which is due to the ability of NTF2 to interact with low affinity with FG containing Nup proteins, as karyopherins do. One of the key steps of nuclear transport is the interaction of importins and exportins with the NLS or NES of a target protein. abstract: Separation of DNA replication and transcription, which occur in the nucleus, from protein synthesis, which occurs in the cytoplasm, allows a more precise regulation of these processes. Selective exchange of macromolecules between the two compartments is mediated by proteins of the nuclear pore complex (NPC). Receptor proteins of the karyopherin family interact with NPC components and transfer their cargos between the nucleus and cytoplasm. Nucleocytoplasmic transport pathways are regulated at multiple levels by modulating the expression or function of individual cargoes, transport receptors, or the transport channel. The regulatory levels have increasingly broad effects on the transport pathways and affect a wide range of processes from gene expression to development and differentiation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088953/ doi: 10.1134/s0026893310020020 id: cord-256156-mywhe6w9 author: Clausen, Thomas Mandel title: SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2 date: 2020-09-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain (RBD). Docking studies suggest a heparin/heparan sulfate-binding site adjacent to the ACE2 binding site. Both ACE2 and heparin can bind independently to spike protein in vitro and a ternary complex can be generated using heparin as a scaffold. Electron micrographs of spike protein suggests that heparin enhances the open conformation of the RBD that binds ACE2. On cells, spike protein binding depends on both heparan sulfate and ACE2. Unfractionated heparin, non-anticoagulant heparin, heparin lyases, and lung heparan sulfate potently block spike protein binding and/or infection by pseudotyped virus and authentic SARS-CoV-2 virus. We suggest a model in which viral attachment and infection involves heparan sulfate-dependent enhancement of binding to ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin presents new therapeutic opportunities. url: https://www.ncbi.nlm.nih.gov/pubmed/32970989/ doi: 10.1016/j.cell.2020.09.033 id: cord-222664-4qyrtzhu author: Coban, Mathew title: Attacking COVID-19 Progression using Multi-Drug Therapy for Synergetic Target Engagement date: 2020-07-06 words: 11220.0 sentences: 638.0 pages: flesch: 46.0 cache: ./cache/cord-222664-4qyrtzhu.txt txt: ./txt/cord-222664-4qyrtzhu.txt summary: We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors; S/Ace2, Tmprss2, Cathepsins L and K, and Mpro to prevent binding, membrane fusion and replication of the virus, respectively. Using a computational pipeline that aimed to expeditiously identify lead compounds against COVID-19, we combined compound library preparation, molecular modeling, and structure simulations to generate an ensemble of conformations and increase high quality docking outcomes against two essential SARS-CoV-2 viral proteins and their host protein interactions; S/Ace2, Tmprss2, Cathepsin L and K, and M pro that are known to control both viral binding, entry and virus replication (Fig. 1A) . abstract: COVID-19 is a devastating respiratory and inflammatory illness caused by a new coronavirus that is rapidly spreading throughout the human population. Over the past 6 months, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has already infected over 11.6 million (25% located in United States) and killed more than 540K people around the world. As we face one of the most challenging times in our recent history, there is an urgent need to identify drug candidates that can attack SARS-CoV-2 on multiple fronts. We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors; S/Ace2, Tmprss2, Cathepsins L and K, and Mpro to prevent binding, membrane fusion and replication of the virus, respectively. All together we generated an ensemble of structural conformations that increase high quality docking outcomes to screen over>6 million compounds including all FDA-approved drugs, drugs under clinical trial (>3000) and an additional>30 million selected chemotypes from fragment libraries. Our results yielded an initial set of 350 high value compounds from both new and FDA-approved compounds that can now be tested experimentally in appropriate biological model systems. We anticipate that our results will initiate screening campaigns and accelerate the discovery of COVID-19 treatments. url: https://arxiv.org/pdf/2007.02557v1.pdf doi: nan id: cord-276456-oa6hh7ky author: Collins, R.N. title: 5.14 The Biophysics of Membrane Fusion date: 2012-05-03 words: 9156.0 sentences: 448.0 pages: flesch: 44.0 cache: ./cache/cord-276456-oa6hh7ky.txt txt: ./txt/cord-276456-oa6hh7ky.txt summary: It will be challenging to distinguish between the lipid simply being a scaffold for a multitude of proteins involved with trafficking at the plasma membrane, and having a direct function in the bilayer rearrangements of fusion and fission. 38 The requirements for specific amino acids at certain positions and for a defined length in the fusion peptide have been further supported by the NMR-solved structure of fusion peptide in detergent micelles and in model lipid membranes 43,52 stabilized by a charge-dipole interaction between the N-terminal Gly and the dipole moment of helix 2 54 (Figure 6 ). The energetics and topology of SNARE complex formation may influence local bending of the a-helix at the interfacial region, which in turn could generate local membrane destabilization to aid fusion ( Figure 8) . How conformational changes amongst SNARE proteins and their accessory factors control the thermodynamics and kinetics of docking, lipid mixing and content mixing after membrane fusion remain open questions. abstract: A crucial interplay between protein conformations and lipid membrane energetics emerges as the guiding principle for the regulation and mechanism of membrane fusion in biological systems. As some of the basics of fusion become clear, a myriad of compelling questions come to the fore. Is the interior of the fusion pore protein or lipid? Why is synaptic release so fast? Why is PIP(2) needed for exocytosis? How does fusion peptide insertion lead to fusion of viruses to cell membranes? What role does the TMD play? How can studies on membrane fission contribute to our understanding of membrane fusion? What exactly are SNARE proteins doing? url: https://api.elsevier.com/content/article/pii/B9780123749208005233 doi: 10.1016/b978-0-12-374920-8.00523-3 id: cord-103430-x6zzuu7v author: Contu, Lara title: Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay date: 2020-10-12 words: 8272.0 sentences: 461.0 pages: flesch: 56.0 cache: ./cache/cord-103430-x6zzuu7v.txt txt: ./txt/cord-103430-x6zzuu7v.txt summary: Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus'' hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. Gene ontology (GO) enrichment analyses of protein complexes that could 10 form between the identified host interactors revealed highly significant GO terms related to 11 translation and Nonsense-mediated mRNA Decay (NMD). In addition to ribosomal proteins, many other RNA binding proteins were also 37 identified as having a potential role in SFV replication (Figure 3a (nsP1, nsP2, nsP3-Z, nsP4, capsid and Env) as well as for the merged list (All baits) was also applied. abstract: The positive-sense, single-stranded RNA alphaviruses pose a potential epidemic threat. Understanding the complex interactions between the viral and the host cell proteins is crucial for elucidating the mechanisms underlying successful virus replication strategies and for developing specific antiviral interventions. Here we present the first comprehensive protein-protein interaction map between the proteins of Semliki Forest Virus (SFV), a mosquito-borne member of the alphaviruses, and host cell proteins. Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus’ hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. In addition to observing a general inhibition of NMD about 4 hours post infection, we also demonstrate that transient expression of the SFV capsid protein is sufficient to inhibit NMD in cells, suggesting that the massive production of capsid protein during the SFV reproduction cycle is responsible for NMD inhibition. url: https://doi.org/10.1101/2020.10.12.335497 doi: 10.1101/2020.10.12.335497 id: cord-316273-vo6j8zb0 author: Cosset, François-Loic title: Cell Entry of Enveloped Viruses date: 2011-02-08 words: 23421.0 sentences: 1013.0 pages: flesch: 40.0 cache: ./cache/cord-316273-vo6j8zb0.txt txt: ./txt/cord-316273-vo6j8zb0.txt summary: On the one hand, they acquired a domain to bind to a specific cellular protein, named "receptor." On the other hand, they developed in a different manner, according to the genus of the virus, a function of fusion that allows the destabilization of the membrane and the opening of a pore through which the genetic material will enter the cell. Thus, we need to distinguish cell surface molecules such as heparan sulfate proteoglycans, DC-SIGN, or integrins that can enhance infections by concentrating retroviruses onto cells (Bounou et al., 2002; Geijtenbeek et al., 2000; Jinno-Oue et al., 2001; Mondor et al., 1998; Pohlmann et al., 2001; Saphire et al., 2001) from authentic receptors that induce conformational changes in EnvGP that are a prerequisite for fusion of the viral and cellular membranes. abstract: Enveloped viruses penetrate their cell targets following the merging of their membrane with that of the cell. This fusion process is catalyzed by one or several viral glycoproteins incorporated on the membrane of the virus. These envelope glycoproteins (EnvGP) evolved in order to combine two features. First, they acquired a domain to bind to a specific cellular protein, named “receptor.” Second, they developed, with the help of cellular proteins, a function of finely controlled fusion to optimize the replication and preserve the integrity of the cell, specific to the genus of the virus. Following the activation of the EnvGP either by binding to their receptors and/or sometimes the acid pH of the endosomes, many changes of conformation permit ultimately the action of a specific hydrophobic domain, the fusion peptide, which destabilizes the cell membrane and leads to the opening of the lipidic membrane. The comprehension of these mechanisms is essential to develop medicines of the therapeutic class of entry inhibitor like enfuvirtide (Fuzeon) against human immunodeficiency virus (HIV). In this chapter, we will summarize the different envelope glycoprotein structures that viruses develop to achieve membrane fusion and the entry of the virus. We will describe the different entry pathways and cellular proteins that viruses have subverted to allow infection of the cell and the receptors that are used. Finally, we will illustrate more precisely the recent discoveries that have been made within the field of the entry process, with a focus on the use of pseudoparticles. These pseudoparticles are suitable for high-throughput screenings that help in the development of natural or artificial inhibitors as new therapeutics of the class of entry inhibitors. url: https://doi.org/10.1016/b978-0-12-380860-8.00004-5 doi: 10.1016/b978-0-12-380860-8.00004-5 id: cord-277424-9aimvogs author: Criscitiello, Michael F. title: Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity date: 2019-11-13 words: 12782.0 sentences: 699.0 pages: flesch: 42.0 cache: ./cache/cord-277424-9aimvogs.txt txt: ./txt/cord-277424-9aimvogs.txt summary: In serum, 103 deiminated proteins were overall identified, including key immune and metabolic mediators including complement components, immunoglobulin-based nanobodies, adiponectin and heat shock proteins. Further deiminated proteins identified in llama serum and serumderived EVs by F95 enrichment and LCeMS/MS analysis included key proteins of camelid innate and adaptive immunity, nuclear proteins, as well as proteins involved in metabolic function. Deimination protein candidates identified here in llama serum and EVs, which are involved in immune, nuclear and metabolic functions, are further discussed below, including where appropriate in a comparative context with relevant human diseases. As a structurally analogous immunoglobulin in shark, new antigen receptor (NAR) (Greenberg et al., 1995; Barelle et al., 2009; Flajnik and Dooley, 2009; De Silva et al., 2019) was recently also found to be deiminated (Criscitiello et al., 2019) , our current finding may provide novel insights into function of these immune proteins and be useful for refinement in therapeutic nanobody development. abstract: Peptidylarginine deiminases (PADs) are phylogenetically conserved calcium-dependent enzymes which post-translationally convert arginine into citrulline in target proteins in an irreversible manner, causing functional and structural changes in target proteins. Protein deimination causes generation of neo-epitopes, affects gene regulation and also allows for protein moonlighting. Furthermore, PADs have been found to be a phylogenetically conserved regulator for extracellular vesicle (EVs) release. EVs are found in most body fluids and participate in cellular communication via transfer of cargo proteins and genetic material. In this study, post-translationally deiminated proteins in serum and serum-EVs are described for the first time in camelids, using the llama (Lama glama L. 1758) as a model animal. We report a poly-dispersed population of llama serum EVs, positive for phylogenetically conserved EV-specific markers and characterised by TEM. In serum, 103 deiminated proteins were overall identified, including key immune and metabolic mediators including complement components, immunoglobulin-based nanobodies, adiponectin and heat shock proteins. In serum, 60 deiminated proteins were identified that were not in EVs, and 25 deiminated proteins were found to be unique to EVs, with 43 shared deiminated protein hits between both serum and EVs. Deiminated histone H3, a marker of neutrophil extracellular trap formation, was also detected in llama serum. PAD homologues were identified in llama serum by Western blotting, via cross reaction with human PAD antibodies, and detected at an expected 70 kDa size. This is the first report of deiminated proteins in serum and EVs of a camelid species, highlighting a hitherto unrecognized post-translational modification in key immune and metabolic proteins in camelids, which may be translatable to and inform a range of human metabolic and inflammatory pathologies. url: https://api.elsevier.com/content/article/pii/S0161589019304833 doi: 10.1016/j.molimm.2019.10.017 id: cord-000003-ejv2xln0 author: Crouch, Erika C title: Surfactant protein-D and pulmonary host defense date: 2000-08-25 words: 6799.0 sentences: 330.0 pages: flesch: 38.0 cache: ./cache/cord-000003-ejv2xln0.txt txt: ./txt/cord-000003-ejv2xln0.txt summary: SP-D, a collagenous calcium-dependent lectin (or collectin), binds to surface glycoconjugates expressed by a wide variety of microorganisms, and to oligosaccharides associated with the surface of various complex organic antigens. The phenotype of macrophages isolated from the lungs of SP-D-deficient mice is altered, and there is circumstantial evidence that abnormal oxidant metabolism and/or increased metalloproteinase expression contributes to the development of emphysema. The potential consequences of this interaction include the following: varying degrees of lectin-dependent aggregation (namely, microbial agglutination), enhanced binding of microorganisms or microbial aggregates to their ''receptors'' on host cells, phagocyte activation, and opsonic enhancement of phagocytosis and killing, potentially involving one or more cellular receptors for SP-D. Although the protein has been immunolocalized to alveolar macrophage membranes and distributes together with SP-D in many different human tissues [10 • ,77], it has not yet been shown to mediate the binding of SP-D to these cells or to participate in signal transduction events. abstract: Surfactant protein-D (SP-D) participates in the innate response to inhaled microorganisms and organic antigens, and contributes to immune and inflammatory regulation within the lung. SP-D is synthesized and secreted by alveolar and bronchiolar epithelial cells, but is also expressed by epithelial cells lining various exocrine ducts and the mucosa of the gastrointestinal and genitourinary tracts. SP-D, a collagenous calcium-dependent lectin (or collectin), binds to surface glycoconjugates expressed by a wide variety of microorganisms, and to oligosaccharides associated with the surface of various complex organic antigens. SP-D also specifically interacts with glycoconjugates and other molecules expressed on the surface of macrophages, neutrophils, and lymphocytes. In addition, SP-D binds to specific surfactant-associated lipids and can influence the organization of lipid mixtures containing phosphatidylinositol in vitro. Consistent with these diverse in vitro activities is the observation that SP-D-deficient transgenic mice show abnormal accumulations of surfactant lipids, and respond abnormally to challenge with respiratory viruses and bacterial lipopolysaccharides. The phenotype of macrophages isolated from the lungs of SP-D-deficient mice is altered, and there is circumstantial evidence that abnormal oxidant metabolism and/or increased metalloproteinase expression contributes to the development of emphysema. The expression of SP-D is increased in response to many forms of lung injury, and deficient accumulation of appropriately oligomerized SP-D might contribute to the pathogenesis of a variety of human lung diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC59549/ doi: 10.1186/rr19 id: cord-016126-i7z0tdrk author: Dangi, Mehak title: Advanced In Silico Tools for Designing of Antigenic Epitope as Potential Vaccine Candidates Against Coronavirus date: 2018-10-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Vaccines are the most economical and potent substitute of available medicines to cure various bacterial and viral diseases. Earlier, killed or attenuated pathogens were employed for vaccine development. But in present era, the peptide vaccines are in much trend and are favoured over whole vaccines because of their superiority over conventional vaccines. These vaccines are either based on single proteins or on synthetic peptides including several B-cell and T-cell epitopes. However, the overall mechanism of action remains the same and works by prompting the immune system to activate the specific B-cell- and T-cell-mediated responses against the pathogen. Rino Rappuoli and others have contributed in this field by plotting the design of the most potent and fully computational approach for discovery of potential vaccine candidates which is popular as reverse vaccinology. This is quite an unambiguous advance for vaccine evolution where one begins with the genome information of the pathogen and ends up with the list of certain epitopes after application of multiple bioinformatics tools. This book chapter is an effort to bring this approach of reverse vaccinology into notice of readers using example of coronavirus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120312/ doi: 10.1007/978-981-13-1562-6_15 id: cord-103255-4k13re9y author: Daniell, Henry title: Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants date: 2001-05-01 words: 4362.0 sentences: 205.0 pages: flesch: 42.0 cache: ./cache/cord-103255-4k13re9y.txt txt: ./txt/cord-103255-4k13re9y.txt summary: The production of recombinant proteins in plants has many potential advantages for generating biopharmaceuticals relevant to clinical medicine. In the decade since the expression and assembly of immunoglobulin (Ig) heavy and light chains into functional antibodies was first shown in transgenic tobacco, plants have proven to be versatile production systems for many forms of antibodies. Other advantages of tobacco include its relative ease of genetic manipulation, production of large numbers of seeds (up to a million per plant) and an impending need to explore alternate uses for this hazardous crop. However, the most attractive species for expressing subunit vaccine components should have high levels of soluble protein that is stable during storage; seed crops such as cereals are particularly suitable. Induction of a protective antibody response to foot and mouth disease in mice following oral or parenteral immunization with alfalfa transgenic plants expressing the viral structural protein VP1 abstract: Abstract The use of plants for medicinal purposes dates back thousands of years but genetic engineering of plants to produce desired biopharmaceuticals is much more recent. As the demand for biopharmaceuticals is expected to increase, it would be wise to ensure that they will be available in significantly larger amounts, on a cost-effective basis. Currently, the cost of biopharmaceuticals limits their availability. Plant-derived biopharmaceuticals are cheap to produce and store, easy to scale up for mass production, and safer than those derived from animals. Here, we discuss recent developments in this field and possible environmental concerns. url: https://api.elsevier.com/content/article/pii/S1360138501019227 doi: 10.1016/s1360-1385(01)01922-7 id: cord-354950-kmpbdvof author: Demurtas, Olivia C. title: Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS date: 2016-02-05 words: 8651.0 sentences: 406.0 pages: flesch: 51.0 cache: ./cache/cord-354950-kmpbdvof.txt txt: ./txt/cord-354950-kmpbdvof.txt summary: Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. In addition, the WHO guidelines for SARS diagnosis, developed during the outbreak in 2003, suggested the use of N-based ELISA for specific IgG detection as confirmatory test of SARS-CoV infection (World Health Organization [WHO] , 2003 SARS: Laboratory diagnostic tests) due to the ability of the host to mount an early antibody response against the N protein (Che et al., 2004) . As the plant-derived recombinant M protein, the M RLV was also specifically recognized by the mouse anti-M pAb ( Figure 6C ) that had previously validated by Immunofluorescence Antibody Assay (IFA) in SARS CoV infected Vero cells (Carattoli et al., 2005) . abstract: Severe acute respiratory syndrome (SARS) is a dangerous infection with pandemic potential. It emerged in 2002 and its aetiological agent, the SARS Coronavirus (SARS-CoV), crossed the species barrier to infect humans, showing high morbidity and mortality rates. No vaccines are currently licensed for SARS-CoV and important efforts have been performed during the first outbreak to develop diagnostic tools. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. For the M protein, this is the first description of production in plants, while for plant-derived N protein we demonstrate that it is recognized by sera of patients from the SARS outbreak in Hong Kong in 2003. The availability of recombinant N and M proteins from plants opens the way to further evaluation of their potential utility for the development of diagnostic and protection/therapy tools to be quickly manufactured, at low cost and with minimal risk, to face potential new highly infectious SARS-CoV outbreaks. url: https://www.ncbi.nlm.nih.gov/pubmed/26904039/ doi: 10.3389/fpls.2016.00054 id: cord-303555-mwu72q7w author: Dent, Paul title: Cell Signaling and Translational Developmental Therapeutics date: 2020-10-06 words: 8877.0 sentences: 556.0 pages: flesch: 49.0 cache: ./cache/cord-303555-mwu72q7w.txt txt: ./txt/cord-303555-mwu72q7w.txt summary: Thus, by the mid-to late-1980s a large body of literature existed which argued that signal transduction pathways consisted of a receptor linked to a large GTP-binding protein which in turn regulated an enzyme that generated "second messengers;" the second messengers would then diffuse throughout the cytosol activating cellular processes, predominantly for metabolism. For the EGFR and other subsequently discovered membrane associated tyrosine kinases, e.g. the non-receptor SCR family and the fibroblast growth factor receptor (FGFR) family, understanding how these enzymes signaled into the cell again initially rested on studies using traditional biochemical methods. [71] [72] [73] [74] [75] [76] Contemporaneously with these studies, researchers were determining how receptor tyrosine kinases regulated RAS family small GTP binding proteins, and other groups determining how RAS proteins signaled downstream off the plasma membrane and into the cytosol. abstract: The relationships between drug pharmacodynamics and subsequent changes in cellular signaling processes are complex. Many in vitro cell signaling studies often use drug concentrations above physiologically safe drug levels achievable in a patient's plasma. Drug companies develop agents to inhibit or modify the activities of specific target enzymes, often without a full consideration that their compounds have additional unknown targets. These two negative sequelae, when published together, become impediments against successful developmental therapeutics and translation because this data distorts our understanding of signaling mechanisms and reduces the probability of successfully translating drug-based concepts from the bench to the bedside. This article will discuss cellular signaling in isolation and as it relates to extant single and combined therapeutic drug interventions. This will lead to a hypothetical series standardized sequential approaches describing a rigorous concept to drug development and clinical translation. url: https://www.sciencedirect.com/science/article/pii/B9780128204726000025 doi: 10.1016/b978-0-12-820472-6.00002-5 id: cord-287410-boxxlopy author: Devi, Arpita title: In silico designing of multi-epitope vaccine construct against human coronavirus infections date: 2020-08-10 words: 7189.0 sentences: 446.0 pages: flesch: 60.0 cache: ./cache/cord-287410-boxxlopy.txt txt: ./txt/cord-287410-boxxlopy.txt summary: Band T-cell epitopes of the spike proteins have been predicted and designed into a multi-epitope vaccine construct. To predict the probable immune response of the designed multi-epitope vaccine construct in human immune system, in silico immune simulations were conducted using the C-ImmSim server (http://150.146.2.1/C-IMMSIM/index.php) (Rapin et al., 2010) . C-ImmSim is a novel in silico approach for the study of the mammalian immune system The tool is a combination of a mesoscopic scale simulator of the immune system with machine learning techniques for molecular-level predictions of major histocompatibility complex (MHC)-peptide-binding interactions, linear B-cell epitope discovery, and protein-protein potential estimation. The antigenicity of the vaccine construct including the adjuvant sequence and His-tag was predicted by the VaxiJen 2.0 server to be 0.6452 with a bacteria model at a threshold of 0.4. abstract: Single stranded RNA viruses were known to cause variety of diseases since many years and are gaining much importance due to pandemic after the identification of a novel corona virus (severe acute respiratory syndrome-coronavirus (SARS-CoV-2)). Seven coronaviruses (CoVs) are known to infect humans and they are OC43 CoV, NL63 CoV, HKU1 CoV, Middle East respiratory syndrome, SARS CoV, and SARS CoV-2. Virus replication weakens the immune system of host thereby altering T-cell count and much of interferon response. Although no vaccine or therapeutic treatment has been approved till now for CoV infection, trials of vaccine against SARS CoV-2 are in progress. One of the epitopes used for vaccine production is of the spike protein on the surface of virus. The work focuses on designing of multi-epitope vaccine construct for treatment of seven human CoV infections using the epitopes present on the spike protein of human CoVs. To address this, immuno-informatics techniques have been employed to design multi-epitope vaccine construct. B- and T-cell epitopes of the spike proteins have been predicted and designed into a multi-epitope vaccine construct. The tertiary structure of the vaccine construct along with the adjuvant has been modelled and the physiochemical properties have been predicted. The multi-epitope vaccine construct has antigenic and non-allergenic property. After validation, refinement and disulphide engineering of the vaccine construct, molecular docking with toll-like receptors (TLRs) have been performed. Molecular dynamics simulation in aqueous environment predicted that the vaccine-TLRs complexes were stable. The vaccine construct is predicted to be able to trigger primary immune response in silico. Communicated by Ramaswamy H. Sarma url: https://doi.org/10.1080/07391102.2020.1804460 doi: 10.1080/07391102.2020.1804460 id: cord-298301-p1zj6jg9 author: Dey, Lopamudra title: Machine Learning Techniques for Sequence-based Prediction of Viral-Host Interactions between SARS-CoV-2 and Human Proteins date: 2020-09-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: COVID-19 (Coronavirus Disease-19), a disease caused by the SARS-CoV-2 virus, has been declared as a pandemic by the World Health Organization on March 11, 2020. Over 15 million people have already been affected worldwide by COVID-19, resulting in more than 0.6 million deaths. Protein-protein interactions (PPIs) play a key role in the cellular process of SARS-CoV-2 virus infection in the human body. Recently a study has reported some SARS-CoV-2 proteins that interact with several human proteins while many potential interactions remain to be identified. METHOD: In this article, various machine learning models are built to predict the PPIs between the virus and human proteins that are further validated using biological experiments. The classification models are prepared based on different sequence-based features of human proteins like amino acid composition, pseudo amino acid composition, and conjoint triad. RESULT: We have built an ensemble voting classifier using SVM(Radial), SVM(Polynomial), and Random Forest technique that gives a greater accuracy, precision, specificity, recall, and F1 score compared to all other models used in the work. A total of 1326 potential human target proteins of SARS-CoV-2 have been predicted by the proposed ensemble model and validated using gene ontology and KEGG pathway enrichment analysis. Several repurposable drugs targeting the predicted interactions are also reported. CONCLUSION: This study may encourage the identification of potential targets for more effective anti-COVID drug discovery. url: https://www.sciencedirect.com/science/article/pii/S2319417020301360?v=s5 doi: 10.1016/j.bj.2020.08.003 id: cord-281528-xy8j5jiv author: Di Paola, Luisa title: The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach date: 2020-06-17 words: 6715.0 sentences: 402.0 pages: flesch: 56.0 cache: ./cache/cord-281528-xy8j5jiv.txt txt: ./txt/cord-281528-xy8j5jiv.txt summary: All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein. We also provided biophysical evidence based on the elastic network modeling (ENM) approach, combined with perturbation-response scanning (PRS) 36 that AMRs in both viruses acted as a mediator of intermolecular allostery between the S protein and ACE2. The map of the participation coefficient projected onto the ribbon structure of the SARS-CoV/ACE2 complex ( Figure 1C ) shows an active region (P > 0) in the junction between the fusion peptide and the trimeric bulk phase of the spike protein. abstract: [Image: see text] SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action. The viral entry and associated infectivity stems from the formation of the SARS-CoV-2 spike protein complex with angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein molecule can be used to elucidate the molecular pathways that can be targeted with allosteric drugs to weaken the spike-ACE2 interaction and, thus, reduce viral infectivity. In this study, we present the results of the application of different computational methods aimed at detecting allosteric sites on the SARS-CoV-2 spike protein. The adopted tools consisted of the protein contact networks (PCNs), SEPAS (Affinity by Flexibility), and perturbation response scanning (PRS) based on elastic network modes. All of these methods were applied to the ACE2 complex with both the SARS-CoV2 and SARS-CoV spike proteins. All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein. url: https://doi.org/10.1021/acs.jproteome.0c00273 doi: 10.1021/acs.jproteome.0c00273 id: cord-312332-rwmuucsp author: Dicker, Kate title: The importance of virion-incorporated cellular RNA-Binding Proteins in viral particle assembly and infectivity date: 2020-09-10 words: 9235.0 sentences: 480.0 pages: flesch: 45.0 cache: ./cache/cord-312332-rwmuucsp.txt txt: ./txt/cord-312332-rwmuucsp.txt summary: title: The importance of virion-incorporated cellular RNA-Binding Proteins in viral particle assembly and infectivity Different proteomic studies have identified hundreds of cellular factors within the particles of several RNA viruses [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] , many of which are RBPs. Here, we discuss the ''knowns'' and ''unknowns'' of the roles that virion-incorporated cellular RBPs could play in the assembly of viral particles and the early steps of infection in the new host cell. Many ivRBPs such as annexins, heat shock family proteins (HSP), peptidylprolyl isomerase A (PPIA -also cyclophilin A), eukaryotic translation elongation factors (EEF), heterogeneous nuclear ribonucleoproteins (HNRNP) or poly(rC) binding protein 1 (PCBP1), have been linked to infection in multiple ways (Fig. S2) , and here we show that they are incorporated in the particles of several viruses (Table S1B) . abstract: RNA is a central molecule in RNA virus biology due to its dual function as messenger and genome. However, the small number of proteins encoded by viral genomes is insufficient to enable virus infection. Hence, viruses hijack cellular RNA-binding proteins (RBPs) to aid replication and spread. In this review we discuss the ‘knowns’ and ‘unknowns’ regarding the contribution of host RBPs to the formation of viral particles and the initial steps of infection in the newly infected cell. Through comparison of the virion proteomes of ten different human RNA viruses, we confirm that a pool of cellular RBPs are typically incorporated into viral particles. We describe here illustrative examples supporting the important functions of these RBPs in viral particle formation and infectivity and we propose that the role of host RBPs in these steps can be broader than previously anticipated. Understanding how cellular RBPs regulate virus infection can lead to the discovery of novel therapeutic targets against viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32921578/ doi: 10.1016/j.semcdb.2020.08.002 id: cord-279432-aik5bo6o author: Digard, Paul title: Complex formation between influenza virus polymerase proteins expressed in Xenopus oocytes date: 1989-07-31 words: 4847.0 sentences: 225.0 pages: flesch: 50.0 cache: ./cache/cord-279432-aik5bo6o.txt txt: ./txt/cord-279432-aik5bo6o.txt summary: As seen in virus-infected cells, all three P proteins associated into an immunoprecipitable complex, suggesting that the system has considerable promise for the reconstruction of an active influenza RNA polymerase. In view of the fact that the P proteins must interact with RNA, it seemed possible that the high sedimentation values obtained for individually expressed PBl and PB2 (Fig. 4) and for complexes containing PBl and PB2 could have arisen from the polypeptides binding to RNA present in the lysate. Furthermore, RNase treatment of lysates containing individually expressed PB2 also failed to affect its sedimentation pattern (not shown), suggesting that the heterogeneous size distribution of the P protein complexes is not the result of association with RNA. Here, we have demonstrated the feasibility of producing all three influenza virus polymerase proteins for functional studies by the translation of in vitro transcribed mRNA analogs in Xenopus oocytes. The three influenza virus polymerase (P) proteins not associated with viral nucleocapsids in the infected cell are in the form of a complex abstract: Abstract All three influenza virus polymerase (P) proteins were expressed in Xenopus oocytes from microinjected in vitro transcribed mRNA analogs, with yields of up to 100 ng per oocyte. To examine the functional state of the Xenopus-expressed P proteins, the polypeptides were tested for their ability to form stable complexes with each other. As seen in virus-infected cells, all three P proteins associated into an immunoprecipitable complex, suggesting that the system has considerable promise for the reconstruction of an active influenza RNA polymerase. Examination of the ability of paired combinations of the P proteins to associate indicated that PB1 contained independent binding sites for PB2 and PA, and so probably formed the backbone of the complex. Sedimentation analysis of free and complexed P proteins indicated that PB1 and PB2 did not exist as free monomers, and that similarly, complexes of all three P proteins did not simply consist of one copy of each protein. The heterodisperse sedimentation rate seen for complexes of all three P proteins did not appear to result from their binding to RNA, suggesting the incorporation of additional polypeptides polymerase complex. url: https://www.ncbi.nlm.nih.gov/pubmed/2741339/ doi: 10.1016/0042-6822(89)90523-0 id: cord-260440-e63pgcir author: Dinjaski, Nina title: Smart polyhydroxyalkanoate nanobeads by protein based functionalization date: 2015-02-24 words: 9066.0 sentences: 520.0 pages: flesch: 35.0 cache: ./cache/cord-260440-e63pgcir.txt txt: ./txt/cord-260440-e63pgcir.txt summary: In vivo PHA modification based on peptide functionalization of PHA nano-beads using GAPs for recombinant protein anchoring to the PHA granule or nonspecific binding and in vivo chemical modification through incorporation of functional group in the side chain of the polymer applying metabolic engineering and systems biology approach. 30 The main advantages of this in vitro cell-free system are: i) the possibility of tight control of nanoparticle disassembly and reassembly process; ii) absence of competition among the recombinant GAP-fusion and wild type proteins; iii) tight control over particle size and immobilized protein/active agent concentration; iv) possibility of endotoxin removal, crucial for the design of every biomedical setup. 18 In completely different context to in vivo tag binding, in vitro synthesized PHA nanoparticles and in vitro hydrophobic binding of PhaP fusion proteins with protein ligands (e.g., mannosylated human α1-acid glycoprotein (hAGP) and human epidermal growth factor (hEGF)) have been reported as another outstanding application of phasins for receptor-mediated drug delivery. abstract: The development of innovative medicines and personalized biomedical approaches calls for new generation easily tunable biomaterials that can be manufactured applying straightforward and low-priced technologies. Production of functionalized bacterial polyhydroxyalkanoate (PHA) nanobeads by harnessing their natural carbon-storage granule production system is a thrilling recent development. This branch of nanobiotechnology employs proteins intrinsically binding the PHA granules as tags to immobilize recombinant proteins of interest and design functional nanocarriers for wide range of applications. Additionally, the implementation of new methodological platforms regarding production of endotoxin free PHA nanobeads using Gram-positive bacteria opened new avenues for biomedical applications. This prompts serious considerations of possible exploitation of bacterial cell factories as alternatives to traditional chemical synthesis and sources of novel bioproducts that could dramatically expand possible applications of biopolymers. FROM THE CLINICAL EDITOR: In the 21st century, we are coming into the age of personalized medicine. There is a growing use of biomaterials in the clinical setting. In this review article, the authors describe the use of natural polyhydroxyalkanoate (PHA) nanoparticulates, which are formed within bacterial cells and can be easily functionalized. The potential uses would include high-affinity bioseparation, enzyme immobilization, protein delivery, diagnostics etc. The challenges of this approach remain the possible toxicity from endotoxin and the high cost of production. url: https://www.sciencedirect.com/science/article/pii/S1549963415000477 doi: 10.1016/j.nano.2015.01.018 id: cord-252147-bvtchcbt author: Domingo-Espín, Joan title: Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles date: 2011-11-15 words: 17193.0 sentences: 888.0 pages: flesch: 39.0 cache: ./cache/cord-252147-bvtchcbt.txt txt: ./txt/cord-252147-bvtchcbt.txt summary: Modular protein engineering, virus-like particles (VLPs), and other self-assembling entities are envisioned as modulatable novel protein nanoparticles able to include many desirable properties in the correct delivery of drugs and nucleic acids. 120 Modular fusion proteins that combine distinct functions required for cell type-specific uptake and intracellular delivery of DNA or drugs present an attractive approach for the development of self-assembling vectors for targeted gene or drug delivery. 215, 216 Although VLP-based vaccines have been primarily developed for their use against the corresponding virus, in the last decades genetic engineering or chemical modifications have been applied in order to generate chimeric VLPs. Thus, on the one hand, commonly short heterologous peptide epitopes or full proteins that are unable to form VLPs or that are unsafe for vaccination have been presented on surface-exposed loops or fused to N-or C-exposed termini of structural viral capsid proteins on VLPs. 154, 161, 210 Different HPV, 217-219 HBV, 220,221 parvovirus, 222, 223 and chimeric polyoma VLPs have been engineered 170, 175 and tested for different applications including vaccination against viral or bacterial diseases, against virus-induced tumors, and more recently, for immunotherapy of nonviral cancer. abstract: The development of genetic engineering techniques has speeded up the growth of the biotechnological industry, resulting in a significant increase in the number of recombinant protein products on the market. The deep knowledge of protein function, structure, biological interactions, and the possibility to design new polypeptides with desired biological activities have been the main factors involved in the increase of intensive research and preclinical and clinical approaches. Consequently, new biological entities with added value for innovative medicines such as increased stability, improved targeting, and reduced toxicity, among others have been obtained. Proteins are complex nanoparticles with sizes ranging from a few nanometers to a few hundred nanometers when complex supramolecular interactions occur, as for example, in viral capsids. However, even though protein production is a delicate process that imposes the use of sophisticated analytical methods and negative secondary effects have been detected in some cases as immune and inflammatory reactions, the great potential of biodegradable and tunable protein nanoparticles indicates that protein-based biotechnological products are expected to increase in the years to come. url: https://doi.org/10.1016/b978-0-12-416020-0.00006-1 doi: 10.1016/b978-0-12-416020-0.00006-1 id: cord-266444-rw94yls8 author: Dominguez Andres, Ana title: SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date: 2020-08-19 words: 5639.0 sentences: 305.0 pages: flesch: 44.0 cache: ./cache/cord-266444-rw94yls8.txt txt: ./txt/cord-266444-rw94yls8.txt summary: The interactome and proteome studies identified cellular processes affected by SARS-CoV-2 infection or specific viral proteins, notably innate immune signaling (19, 20, 23, (28) (29) (30) , ubiquitin ligase activities (19, 20, 23, (28) (29) (30) , p38 mitogenactivated protein kinase (MAPK) signaling (19, 20, 23, (28) (29) (30) . To assess if there were notable differences in the intensity of the changes in protein abundance in response to proteasome inhibition, we calculated relative changes in protein abundance between control and ORF9c-expressing cells from both the DMSO and MG132 conditions for proteins associated with IFN signaling or the ubiquitin proteasome (UBP) system and antigen presentation (Fig. 2D ). In contrast to the proteomic results that revealed predominant downregulation of proteins following ORF9c expression, RNA-seq analysis showed a similar number of transcripts were increased or decreased in the presence or absence of MG132 (Fig. 3A, table S2 ). abstract: Disrupted antiviral immune responses are associated with severe COVID-19, the disease caused by SAR-CoV-2. Here, we show that the 73-amino-acid protein encoded by ORF9c of the viral genome contains a putative transmembrane domain, interacts with membrane proteins in multiple cellular compartments, and impairs antiviral processes in a lung epithelial cell line. Proteomic, interactome, and transcriptomic analyses, combined with bioinformatic analysis, revealed that expression of only this highly unstable small viral protein impaired interferon signaling, antigen presentation, and complement signaling, while inducing IL-6 signaling. Furthermore, we showed that interfering with ORF9c degradation by either proteasome inhibition or inhibition of the ATPase VCP blunted the effects of ORF9c. Our study indicated that ORF9c enables immune evasion and coordinates cellular changes essential for the SARS-CoV-2 life cycle. One-sentence summary SARS-CoV-2 ORF9c is the first human coronavirus protein localized to membrane, suppressing antiviral response, resembling full viral infection. url: https://doi.org/10.1101/2020.08.18.256776 doi: 10.1101/2020.08.18.256776 id: cord-306111-wn1gxhk9 author: Dommett, R. M. title: Mannose‐binding lectin in innate immunity: past, present and future date: 2006-09-01 words: 9061.0 sentences: 436.0 pages: flesch: 43.0 cache: ./cache/cord-306111-wn1gxhk9.txt txt: ./txt/cord-306111-wn1gxhk9.txt summary: Third MBL mutation in codon 52 (variant D) described (52) 1995 Polymorphisms found in promoter region of MBL gene (55) 1997 Second MASP found to activate complement (20) MBL mutations are an important risk factor for infections in children (132) 1998 Reconstitution of opsonizing activity by infusion of purified MBL into MBL-deficient humans (112) 1999 Truncated form of MASP-2 -MAp19 (21) 2000 Complement-activating complex of ficolins and MASP (133) MBL shown to bind to clinically relevant organisms (15) Structural aspects of MBL abstract: The human collectin, mannose‐binding lectin (MBL), is an important protein of the humoral innate immune system. With multiple carbohydrate‐recognition domains, it is able to bind to sugar groups displayed on the surfaces of a wide range of microorganisms and thereby provide first‐line defence. Importantly, it also activates the complement system through a distinctive third pathway, independent of both antibody and the C1 complex. Three single point mutations in exon 1 of the expressed human MBL‐2 gene appear to impair the generation of functional oligomers. Such deficiencies of functional protein are common in certain populations, e.g. in sub‐Saharan Africa, but virtually absent in others, e.g. indigenous Australians. MBL disease association studies have been a fruitful area of research and implicate a role for MBL in infective, inflammatory and autoimmune disease processes. Overall, there appears to be a genetic balance in which individuals generally benefit from high levels of the protein. However, in certain situations, reduced levels of circulating MBL may be beneficial to the host and this may explain the persistence of the deleterious gene polymorphisms in many population groups. url: https://www.ncbi.nlm.nih.gov/pubmed/16948640/ doi: 10.1111/j.1399-0039.2006.00649.x id: cord-298251-u36lb44w author: Donaldson, Julie G. title: Arf Family G Proteins and their regulators: roles in membrane transport, development and disease date: 2011-05-18 words: 10702.0 sentences: 519.0 pages: flesch: 44.0 cache: ./cache/cord-298251-u36lb44w.txt txt: ./txt/cord-298251-u36lb44w.txt summary: Members of the ADP-ribosylation factor (ARF) family of guanine-nucleotide-binding (G) proteins, including the ARF-like (ARL) proteins and SAR1, regulate membrane traffic and organelle structure by recruiting cargo-sorting coat proteins, modulating membrane lipid composition, and interacting with regulators of other G proteins. ARF proteins at the trans-Golgi network (TGN) also recruit heterotetrameric clathrin adaptor protein 1 (AP1), AP3 and AP4, as well as the three monomeric Golgi-localized, γ-ear-containing, ADP-ribosylation factor-binding Figure 1 | The domain structure and regulation of ARF and ARLs. a | A schematic of representative ADP-ribosylation factor (ARF), SAR1 and ARF-like (ARL) proteins, indicating the conserved amino-terminal amphipathic helix and the protein-specific lipid modifications at the N terminus. ARF6 at the plasma membrane can regulate the membrane lipid composition, alterations in cortical actin to drive protrusions (for example, during cell migration), and endocytosis of ligand-activated guanine-nucleotide-binding (G) protein-coupled receptors (GPCR) via clathrin-dependent endocytosis. abstract: Members of the ADP-ribosylation factor (ARF) family of guanine-nucleotide-binding (G) proteins, including the ARF-like (ARL) proteins and SAR1, regulate membrane traffic and organelle structure by recruiting cargo-sorting coat proteins, modulating membrane lipid composition, and interacting with regulators of other G proteins. New roles of ARF and ARL proteins are emerging, including novel functions at the Golgi complex and in cilia formation. Their function is under tight spatial control, which is mediated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that catalyse GTP exchange and hydrolysis, respectively. Important advances are being gained in our understanding of the functional networks that are formed not only by the GEFs and GAPs themselves but also by the inactive forms of the ARF proteins. url: https://www.ncbi.nlm.nih.gov/pubmed/21587297/ doi: 10.1038/nrm3117 id: cord-010681-tmpxs9og author: Dondapati, Srujan Kumar title: Cell-Free Protein Synthesis: A Promising Option for Future Drug Development date: 2020-03-20 words: 10674.0 sentences: 487.0 pages: flesch: 36.0 cache: ./cache/cord-010681-tmpxs9og.txt txt: ./txt/cord-010681-tmpxs9og.txt summary: aatRNA aminoacyl-tRNA, AAS aminoacyl-tRNA synthetase, ATP adenosine triphosphate, EF elongation factor, GSH glutathione, GSSG glutathione-disulfide, GTP guanosine-5''-triphosphate, IF initiation factor, IRES internal ribosome entry site, MP membrane protein, nCAA non-canonical amino acid, PDI protein disulfide isomerase, PEG polyethylene glycol, PTM post-translational modification, R ribosomes, t-RNA transfer RNA, TF transcription factor, UTR untranslated region, VLP virus like particle Chinese hamster ovary (CHO) Mimic the CHO cell-based production PTMs (N-glycosylation, disulfide bridging, and lipidation) Suitable for a wide range of eukaryotic and complex proteins Presence of translational active endogenous microsomes [45] High yields in CECF mode Endotoxin free Lysates used for point-of-care testing [30] Low yields especially in the batch mode [58] Cost ineffective and difficult to establish unlike E. abstract: Proteins are the main source of drug targets and some of them possess therapeutic potential themselves. Among them, membrane proteins constitute approximately 50% of the major drug targets. In the drug discovery pipeline, rapid methods for producing different classes of proteins in a simple manner with high quality are important for structural and functional analysis. Cell-free systems are emerging as an attractive alternative for the production of proteins due to their flexible nature without any cell membrane constraints. In a bioproduction context, open systems based on cell lysates derived from different sources, and with batch-to-batch consistency, have acted as a catalyst for cell-free synthesis of target proteins. Most importantly, proteins can be processed for downstream applications like purification and functional analysis without the necessity of transfection, selection, and expansion of clones. In the last 5 years, there has been an increased availability of new cell-free lysates derived from multiple organisms, and their use for the synthesis of a diverse range of proteins. Despite this progress, major challenges still exist in terms of scalability, cost effectiveness, protein folding, and functionality. In this review, we present an overview of different cell-free systems derived from diverse sources and their application in the production of a wide spectrum of proteins. Further, this article discusses some recent progress in cell-free systems derived from Chinese hamster ovary and Sf21 lysates containing endogenous translocationally active microsomes for the synthesis of membrane proteins. We particularly highlight the usage of internal ribosomal entry site sequences for more efficient protein production, and also the significance of site-specific incorporation of non-canonical amino acids for labeling applications and creation of antibody drug conjugates using cell-free systems. We also discuss strategies to overcome the major challenges involved in commercializing cell-free platforms from a laboratory level for future drug development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211207/ doi: 10.1007/s40259-020-00417-y id: cord-318749-k91oku7h author: Dong, Hui-Jun title: Selective regulation in ribosome biogenesis and protein production for efficient viral translation date: 2020-10-29 words: 7265.0 sentences: 384.0 pages: flesch: 38.0 cache: ./cache/cord-318749-k91oku7h.txt txt: ./txt/cord-318749-k91oku7h.txt summary: Recently reported studies have demonstrated that ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs) act as multifaceted regulators in selective translation of viral transcripts. Similarly, ribosomes are required for the protein synthesis of host cells and viruses, but the biogenesis factor RBFs can also impact the proliferation of virus and cell-intrinsic immune responses. The multifunctional nucleolar phosphoprotein nucleophosmin (NPM) plays a lead role in ribosome biogenesis to stimulate RNA Pol I-dependent transcription (Li and Hann 2013) and regulates SARS-CoV, IBV, HIV-1, HCV Recruited by viral proteins to facilitate viral replication Chen et al. RPS25 deletion in yeast or mammalian cells has minimal effects on cellular protein synthesis, which implies that this ribosomal protein may be selectively required for viral IRES-mediated translation (Jack et al. Conservation of multifunctional ribosomal protein metallopanstimulin-1 (RPS27) through complex evolution demonstrates its key role in growth regulation in Archaea, eukaryotic cells, DNA repair, translation and viral replication abstract: As intracellular parasites, viruses depend heavily on host cell structures and their functions to complete their life cycle and produce new viral particles. Viruses utilize or modulate cellular translational machinery to achieve efficient replication; the role of ribosome biogenesis and protein synthesis in viral replication particularly highlights the importance of the ribosome quantity and/or quality in controlling viral protein synthesis. Recently reported studies have demonstrated that ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs) act as multifaceted regulators in selective translation of viral transcripts. Here we summarize the recent literature on RBFs and RPs and their association with subcellular redistribution, post-translational modification, enzyme catalysis, and direct interaction with viral proteins. The advances described in this literature establish a rationale for targeting ribosome production and function in the design of the next generation of antiviral agents. url: https://www.ncbi.nlm.nih.gov/pubmed/33124672/ doi: 10.1007/s00203-020-02094-5 id: cord-354030-8tfg881h author: Dong, Rong title: Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches date: 2020-07-28 words: 7983.0 sentences: 442.0 pages: flesch: 52.0 cache: ./cache/cord-354030-8tfg881h.txt txt: ./txt/cord-354030-8tfg881h.txt summary: The realm of immunoinformatics tools considers the mechanism of the host immune response to yield additional methodologies in the design of vaccine against diseases are cost-effective and convenient, as in silico predictions can reduce the number of experiments needed (13, 14) . In this present, we employed immunoinformatics to predict multiple immunogenic proteins from the SARS-CoV-2 proteome and thereby design a multi-epitope vaccine. developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . A vaccine based on the spike protein could induce antibodies to block SARS-COV-2 binding and fusion or neutralize virus infection (18) , as well as induce harmful immune responses that cause liver damage (19) . To design an effective vaccine, we selected the SARS-CoV-2 protein through the above-mentioned methods for epitope prediction. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach abstract: COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1–14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as in silico predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the β-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed in silico cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections. url: https://doi.org/10.3389/fimmu.2020.01784 doi: 10.3389/fimmu.2020.01784 id: cord-350935-p6euuop3 author: Doğan, Tunca title: CROssBAR: Comprehensive Resource of Biomedical Relations with Deep Learning Applications and Knowledge Graph Representations date: 2020-09-15 words: 7066.0 sentences: 298.0 pages: flesch: 45.0 cache: ./cache/cord-350935-p6euuop3.txt txt: ./txt/cord-350935-p6euuop3.txt summary: We aimed to address this issue by constructing a new biological and biomedical data resource, CROssBAR, a comprehensive system that integrates large-scale biomedical data from various resources and store them in a new NoSQL database, enrich these data with deep-learning-based prediction of relations between numerous biomedical entities, rigorously analyse the enriched data to obtain biologically meaningful modules and display them to users via easy-to-interpret, interactive and heterogenous knowledge graph (KG) representations within an open access, user-friendly and online web-service at https://crossbar.kansil.org. In this project, we aimed to address the current shortcomings by developing a comprehensive open access biomedical system entitled CROssBAR via integrating various biological databases to each other, inferring the missing relations between existing data points, and constructing informative knowledge graphs based on specific biomedical components/terms such as a disease/phenotype, biological process, gene/protein and drug/compound, or specific combinations of them. abstract: Systemic analysis of available large-scale biological and biomedical data is critical for developing novel and effective treatment approaches against both complex and infectious diseases. Owing to the fact that different sections of the biomedical data is produced by different organizations/institutions using various types of technologies, the data are scattered across individual computational resources, without any explicit relations/connections to each other, which greatly hinders the comprehensive multi-omics-based analysis of data. We aimed to address this issue by constructing a new biological and biomedical data resource, CROssBAR, a comprehensive system that integrates large-scale biomedical data from various resources and store them in a new NoSQL database, enrich these data with deep-learning-based prediction of relations between numerous biomedical entities, rigorously analyse the enriched data to obtain biologically meaningful modules and display them to users via easy-to-interpret, interactive and heterogenous knowledge graph (KG) representations within an open access, user-friendly and online web-service at https://crossbar.kansil.org. As a use-case study, we constructed CROssBAR COVID-19 KGs (available at: https://crossbar.kansil.org/covid_main.php) that incorporate relevant virus and host genes/proteins, interactions, pathways, phenotypes and other diseases, as well as known and completely new predicted drugs/compounds. Our COVID-19 graphs can be utilized for a systems-level evaluation of relevant virus-host protein interactions, mechanisms, phenotypic implications and potential interventions. url: https://doi.org/10.1101/2020.09.14.296889 doi: 10.1101/2020.09.14.296889 id: cord-319809-33i6lzjd author: Drew, Elliot D. title: Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity date: 2020-07-01 words: 4573.0 sentences: 210.0 pages: flesch: 57.0 cache: ./cache/cord-319809-33i6lzjd.txt txt: ./txt/cord-319809-33i6lzjd.txt summary: title: Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity RESULTS: Our analyses of this structure have revealed a key potentially druggable pocket where it might be viable to bind pharmaceutical agents to inhibit its ability to infect human cells. The results from the three methods, Autodock vina [12] , Smina [13] and Ledock [14] , were used to generate a list of 4358 poses of commercially-available drugs capable of binding into this Covid-19 spike protein pocket. This study provides a suggested list of pharmaceutical agents, identifying some of them as being from related structure families, that are available on the market and have been sanctioned for use in humans that have been shown to be capable of binding into a druggable pocket in the spike protein of Covid-19. abstract: BACKGROUND: Following the recent outbreak of the new coronavirus pandemic (Covid-19), the rapid determination of the structure of the homo-trimeric spike glycoprotein has prompted the study reported here. The aims were to identify potential “druggable” binding pockets in the protein and, if located, to virtual screen pharmaceutical agents currently in use for predicted affinity to these pockets which might be useful to restrict, reduce, or inhibit the infectivity of the virion. RESULTS: Our analyses of this structure have revealed a key potentially druggable pocket where it might be viable to bind pharmaceutical agents to inhibit its ability to infect human cells. This pocket is found at the inter-chain interface that exists between two domains prior to the virion binding to human Angiotensin Converting Enzyme 2 (ACE2) protein. One of these domains is the highly mobile receptor binding domain, which must move into position to interact with ACE2, which is an essential feature for viral entry to the host cell. Virtual screening with a library of purchasable drug molecules has identified pharmaceuticals currently in use as prescription and over the counter medications that, in silico, readily bind into this pocket. CONCLUSIONS: This study highlights possible drugs already in use as pharmaceuticals that may act as agents to interfere with the movements of the domains within this protein essential for the infectivity processes and hence might slow, or even halt, the infection of host cells by this new coronavirus. As these are existing pharmaceuticals already approved for use in humans, this knowledge could accelerate their roll-out, through repurposing, for affected individuals and help guide the efforts of other researchers in finding effective treatments for the disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32611313/ doi: 10.1186/s12860-020-00294-x id: cord-328003-yovp8squ author: Duan, Liangwei title: The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date: 2020-10-07 words: 7346.0 sentences: 386.0 pages: flesch: 46.0 cache: ./cache/cord-328003-yovp8squ.txt txt: ./txt/cord-328003-yovp8squ.txt summary: Here, we provide a comprehensive overview of the wealth of research related to the SARS-CoV-2 S glycoprotein biosynthesis, structure, function, and antigenicity, aiming to provide useful insights into the design and development of the S protein-based vaccines as well as therapeutics to prevent or treat the ongoing global spread of SARS-CoV-2/COVID-19. Prefusion structures of human coronavirus HKU1 (HCoV-HKU1) and mouse hepatitis virus S protein ectodomains without two consecutive proline mutations reveal only fully closed conformation (37, 42) , similar to that observed for a full-length, wild-type prefusion form of the SARS-CoV-2 S glycoprotein (41) . Therefore, SARS-CoV-2 evades immune surveillance also through conformational masking, which is well-documented for HIV-1 (43, 44) ; while at the same time, the S protein could transiently sample the functional state to engage ACE2, consistent with the notion that the fusion glycoprotein of highly pathogenic viruses have evolved to perform its functions while evading host neutralizing antibody responses. abstract: The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a grave threat to global public health and imposes a severe burden on the entire human society. Like other coronaviruses, the SARS-CoV-2 genome encodes spike (S) glycoproteins, which protrude from the surface of mature virions. The S glycoprotein plays essential roles in virus attachment, fusion and entry into the host cell. Surface location of the S glycoprotein renders it a direct target for host immune responses, making it the main target of neutralizing antibodies. In the light of its crucial roles in viral infection and adaptive immunity, the S protein is the focus of most vaccine strategies as well as therapeutic interventions. In this review, we highlight and describe the recent progress that has been made in the biosynthesis, structure, function, and antigenicity of the SARS-CoV-2 S glycoprotein, aiming to provide valuable insights into the design and development of the S protein-based vaccines as well as therapeutics. url: https://www.ncbi.nlm.nih.gov/pubmed/33117378/ doi: 10.3389/fimmu.2020.576622 id: cord-286603-4p3t0vre author: Duan, Zhiqiang title: TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein date: 2020-06-27 words: 10674.0 sentences: 464.0 pages: flesch: 40.0 cache: ./cache/cord-286603-4p3t0vre.txt txt: ./txt/cord-286603-4p3t0vre.txt summary: title: TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein Therefore, the reduced viral RNA synthesis and transcription caused by M/NLS mutation might be one of the reasons responsible for the attenuated replication of rSS1GFP-M/NLSm. Virus-host protein interactions based on quantitative proteomics analysis have become important methods in understanding cellular proteins involved in virus replication and pathogenesis [22, 23, 41, 42] . Therefore, together with the above results, we speculated that the relatively decreased expression of DEPs involved in ribosome structure, protein posttranslational modification and trafficking due to the disrupted nuclear accumulation of M protein affected viral protein synthesis and budding, which might be the third reason responsible for the attenuated replication of rSS1GFP-M/NLSm. Inflammatory responses are important aspects of the innate immune system during virus infection. abstract: Nuclear localization of cytoplasmic RNA virus proteins mediated by intrinsic nuclear localization signal (NLS) plays essential roles in successful virus replication. We previously reported that NLS mutation in the matrix (M) protein obviously attenuates the replication and pathogenicity of Newcastle disease virus (NDV), but the attenuated replication mechanism remains unclear. In this study, we showed that M/NLS mutation not only disrupted M’s nucleocytoplasmic trafficking characteristic but also impaired viral RNA synthesis and transcription. Using TMT-based quantitative proteomics analysis of BSR-T7/5 cells infected with the parental NDV rSS1GFP and the mutant NDV rSS1GFP-M/NLSm harboring M/NLS mutation, we found that rSS1GFP infection stimulated much greater quantities and more expression changes of differentially expressed proteins involved in host cell transcription, ribosomal structure, posttranslational modification, and intracellular trafficking than rSS1GFP-M/NLSm infection. Further in-depth analysis revealed that the dominant nuclear accumulation of M protein inhibited host cell transcription, RNA processing and modification, protein synthesis, posttranscriptional modification and transport; and this kind of inhibition could be weakened when most of M protein was confined outside the nucleus. More importantly, we found that the function of M protein in the cytoplasm effected the inhibition of TIFA expression in a dose-dependent manner, and promoted NDV replication by down-regulating TIFA/TRAF6/NF-κB-mediated production of cytokines. It was the first report about the involvement of M protein in NDV immune evasion. Taken together, our findings demonstrate that NDV replication is closely related to the nucleocytoplasmic trafficking of M protein, which accelerates our understanding of the molecular functions of NDV M protein. url: https://doi.org/10.1080/21505594.2020.1770482 doi: 10.1080/21505594.2020.1770482 id: cord-014661-mrh2pbi6 author: Dumitrascu, Georgiana R. title: Critical physiological and pathological functions of Forkhead Box O tumor suppressors date: 2013-12-31 words: 9235.0 sentences: 419.0 pages: flesch: 38.0 cache: ./cache/cord-014661-mrh2pbi6.txt txt: ./txt/cord-014661-mrh2pbi6.txt summary: FOXO proteins are considered unique cellular targets, regulating a wide variety of critical cellular processes, such as: apoptosis, oxidative stress, DNA damage repair, cell cycle, stem cell proliferation and maintenance, metabolism, angiogenesis, vascular tone, cardiovascular development, fertility, immune response and neuronal survival 4, 20 . Hence, the FOXO transcription factors control the expression of a wide spectrum of genes that regulate essential physiological cellular processes, such as cell death/cell survival, cell cycle, cell proliferation, cell differentiation/development, angiogenesis, cell metabolism, stress response and stem cell maintenance 33,34,35,36,37,38 (Figure 2) . Moreover, the consensus FOXO recognition element (FRE) -(G/C)(T/A)AA(C/T)AA -which differs from that of other forkhead proteins, seems to have a very important role in both apoptotic pathways, since matching functional FRE sites have been identified in the promoters of FOXO target genes encoding Fas ligand (FasL), insulin like growth factorbinding protein 1 (IGFBP1), the apoptotic regulator Bcl-2 interacting mediator of cell death (Bim) and others 30 . abstract: The Forkhead box, subclass O (FOXO) proteins are critical transcription factors, ubiquitously expressed in the human body. These proteins are characterized by a remarkable functional diversity, being involved in cell cycle arrest, apoptosis, oxidative detoxification, DNA damage repair, stem cell maintenance, cell differentiation, cell metabolism, angiogenesis, cardiac development, aging and others. In addition, FOXO have critical implications in both normal and cancer stem cell biology. New strategies to modulate FOXO expression and activity may now be developed since the discovery of novel FOXO regulators and non-coding RNAs (such as microRNAs) targeting FOXO transcription factors. This review focuses on physiological and pathological functions of FOXO proteins and on their action as fine regulators of cell fate and context-dependent cell decisions. A better understanding of the structure and critical functions of FOXO transcription factors and tumor suppressors may contribute to the development of novel therapies for cancer and other diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941590/ doi: 10.15190/d.2013.5 id: cord-009614-lbjesv8y author: Durmuş Tekir, Saliha D. title: Systems biology of pathogen‐host interaction: Networks of protein‐protein interaction within pathogens and pathogen‐human interactions in the post‐genomic era date: 2012-11-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Infectious diseases comprise some of the leading causes of death and disability worldwide. Interactions between pathogen and host proteins underlie the process of infection. Improved understanding of pathogen‐host molecular interactions will increase our knowledge of the mechanisms involved in infection, and allow novel therapeutic solutions to be devised. Complete genome sequences for a number of pathogenic microorganisms, as well as the human host, has led to the revelation of their protein‐protein interaction (PPI) networks. In this post‐genomic era, pathogen‐host interactions (PHIs) operating during infection can also be mapped. Detailed systematic analyses of PPI and PHI data together are required for a complete understanding of pathogenesis of infections. Here we review the striking results recently obtained during the construction and investigation of these networks. Emphasis is placed on studies producing large‐scale interaction data by high‐throughput experimental techniques. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161785/ doi: 10.1002/biot.201200110 id: cord-033010-o5kiadfm author: Durojaye, Olanrewaju Ayodeji title: Potential therapeutic target identification in the novel 2019 coronavirus: insight from homology modeling and blind docking study date: 2020-10-02 words: 8125.0 sentences: 375.0 pages: flesch: 53.0 cache: ./cache/cord-033010-o5kiadfm.txt txt: ./txt/cord-033010-o5kiadfm.txt summary: RESULTS: This study describes the detailed computational process by which the 2019-nCoV main proteinase coding sequence was mapped out from the viral full genome, translated and the resultant amino acid sequence used in modeling the protein 3D structure. Our current study took advantage of the availability of the SARS CoV main proteinase amino acid sequence to map out the nucleotide coding region for the same protein in the 2019-nCoV. The predicted secondary structure composition shows a high degree of alpha helix and beta sheets, respectively, occupying 45 and 47% of the total residues with the percentage loop occupancy at 8% regarded as comparative modeling, constructs atomic models based on known structures or structures that have been determined experimentally and likewise share more than 40% sequence homology. abstract: BACKGROUND: The 2019-nCoV which is regarded as a novel coronavirus is a positive-sense single-stranded RNA virus. It is infectious to humans and is the cause of the ongoing coronavirus outbreak which has elicited an emergency in public health and a call for immediate international concern has been linked to it. The coronavirus main proteinase which is also known as the 3C-like protease (3CLpro) is a very important protein in all coronaviruses for the role it plays in the replication of the virus and the proteolytic processing of the viral polyproteins. The resultant cytotoxic effect which is a product of consistent viral replication and proteolytic processing of polyproteins can be greatly reduced through the inhibition of the viral main proteinase activities. This makes the 3C-like protease of the coronavirus a potential and promising target for therapeutic agents against the viral infection. RESULTS: This study describes the detailed computational process by which the 2019-nCoV main proteinase coding sequence was mapped out from the viral full genome, translated and the resultant amino acid sequence used in modeling the protein 3D structure. Comparative physiochemical studies were carried out on the resultant target protein and its template while selected HIV protease inhibitors were docked against the protein binding sites which contained no co-crystallized ligand. CONCLUSION: In line with results from this study which has shown great consistency with other scientific findings on coronaviruses, we recommend the administration of the selected HIV protease inhibitors as first-line therapeutic agents for the treatment of the current coronavirus epidemic. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529470/ doi: 10.1186/s43042-020-00081-5 id: cord-342118-fsmuqktd author: Dyakov, Ilya N. title: FN3 protein fragment containing two type III fibronectin domains from B. longum GT15 binds to human tumor necrosis factor alpha in vitro date: 2020-08-06 words: 2445.0 sentences: 150.0 pages: flesch: 57.0 cache: ./cache/cord-342118-fsmuqktd.txt txt: ./txt/cord-342118-fsmuqktd.txt summary: Previously, based on the analysis of the genomes of 34 species of bifidobacteria, we 233 identified and characterized a species-specific cluster of PFNA genes, which consists of To develop a sandwich ELISA assay that would allow us to check the ability of the 298 recombinant FN3 protein to bind human cytokines, we raised polyclonal antibodies 299 specific to the recombinant FN3 protein. The resulting affinity 302 purified and concentrated preparation contained 1 mg of FN3-specific rabbit polyclonal 303 antibodies per 1 mL and was highly active -specific interaction with the FN3 protein 304 was detected even after 1:820000 dilution. To exclude the possibility of blockage of the cytokine-binding motif of the FN3 335 protein and its nonspecific adsorption onto the solid surface, we employed ELISA 336 scheme 3 described in the materials and methods section: The FN3-specific rabbit 337 polyclonal antibodies were first adsorbed onto the solid surface after which the FN3 338 protein was added as a "second layer". abstract: Most species of the genus Bifidobacterium contain the gene cluster PFNA, which is presumably involved in the species-specific communication between bacteria and their hosts. The gene cluster PFNA consists of five genes including fn3, which codes for a protein containing two fibronectin type III domains. Each fibronectin domain contains sites similar to cytokine-binding sites of human receptors. Based on this finding we assumed that this protein would bind specifically to human cytokines in vitro. We cloned a fragment of the fn3 gene (1503 bp; 501 aa) containing two fibronectin domains, from the strain B. longum subsp. longum GT15. After cloning the fragment into the expression vector pET16b and expressing it in E. coli, the protein product was purified to a homogenous state for further analysis. Using the immunoferment method, we tested the purified fragment's ability to bind the following human cytokines: IL-1β, IL-6, IL-10, TNFα. We developed a sandwich ELISA system to detect any specific interactions between the purified protein and any of the studied cytokines. We found that the purified protein fragment only binds to TNFα. url: https://api.elsevier.com/content/article/pii/S1075996420301037 doi: 10.1016/j.anaerobe.2020.102247 id: cord-320092-0qnvydux author: Ehsani, Sepehr title: COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein date: 2020-10-16 words: 7536.0 sentences: 406.0 pages: flesch: 45.0 cache: ./cache/cord-320092-0qnvydux.txt txt: ./txt/cord-320092-0qnvydux.txt summary: An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. c The position of the disulfide bonds in the sequence of the mature human hepcidin is illustrated along with the potential palmitoylation residues (ten cysteines) of the cytoplasmic tail of the SARS-CoV-2 spike protein. If the sequence similarity reported here is actually playing a significant role at the cellular level, could it be that, although the cellular localizations appear to be different based on current knowledge, the SARS-CoV-2 spike protein cytoplasmic tail can partly mimic the structure of hepcidin and interact with ferroportin? In addition, a notyet-fully-established link of relevance here is the observations of a Kawasaki-disease-like systemic vasculitis syndrome in children infected with the novel Fig. 3 Summary of salient facets of coronavirus spike protein and human hepcidin biology. abstract: The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we report a distant sequence similarity between the cysteine-rich cytoplasmic tail of the coronavirus spike protein and the hepcidin protein that is found in humans and other vertebrates. Hepcidin is thought to be the key regulator of iron metabolism in humans through its inhibition of the iron-exporting protein ferroportin. An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. The question of possible homology and an evolutionary connection between the viral spike protein and hepcidin is not assessed in this report, but some scenarios for its study are discussed. url: https://doi.org/10.1186/s13062-020-00275-2 doi: 10.1186/s13062-020-00275-2 id: cord-334511-lx9608vy author: Emwas, Abdul-Hamid title: NMR as a “Gold Standard” Method in Drug Design and Discovery date: 2020-10-09 words: 29224.0 sentences: 1507.0 pages: flesch: 47.0 cache: ./cache/cord-334511-lx9608vy.txt txt: ./txt/cord-334511-lx9608vy.txt summary: The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . Clearly, combining virtual screening with NMR-based methods is advantageous in studying how ligands (drugs) bind and interact with targets (proteins) of interest. The interactions between targets (proteins) and ligands (small molecules) can be analyzed independently of the biological systems by using ''cell-based'' NMR drug design approaches. abstract: Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a “gold standard” platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development. url: https://doi.org/10.3390/molecules25204597 doi: 10.3390/molecules25204597 id: cord-348360-20eq5meh author: Esposito, Dominic title: Optimizing high-yield production of SARS-CoV-2 soluble spike trimers for serology assays date: 2020-06-04 words: 3438.0 sentences: 158.0 pages: flesch: 49.0 cache: ./cache/cord-348360-20eq5meh.txt txt: ./txt/cord-348360-20eq5meh.txt summary: To improve the yield of spike protein and support the high demand for antigens in serology assays, we investigated several recombinant protein expression variables by altering the incubation temperature, harvest time, chromatography strategy, and final protein manipulation. Thus, the work presented here is intended to provide a robust method for those wishing to reliably produce SARS CoV-2 spike protein in quantities sufficient for serology assays, structural biology, or simply to better understand some of the production variables affecting the yield. Nevertheless, the approaches outlined here allowed us to improve the production yield of spike protein significantly by modifying cell culture temperature and harvest time, as well as improving the purification process. To produce SARS-CoV-2 antigens for the development of serology assays, we initially followed standard procedures for secreted protein production: transfection using the manufacturer''s protocols, expression at 37°C, harvest at three days post-transfection, tangential flow filtration of the culture supernatant, immobilized metal ion chromatography with linear gradient elution, and size exclusion chromatography. abstract: The SARS-CoV-2 spike trimer is the primary antigen for several serology assays critical to determining the extent of SARS-CoV-2 exposure in the population. Until stable cell lines are developed to increase the titer of this secreted protein in mammalian cell culture, the low yield of spike protein produced from transient transfection of HEK293 cells will be a limiting factor for these assays. To improve the yield of spike protein and support the high demand for antigens in serology assays, we investigated several recombinant protein expression variables by altering the incubation temperature, harvest time, chromatography strategy, and final protein manipulation. Through this investigation, we developed a simplified and robust purification strategy that consistently yields 5 mg of protein per liter of expression culture for two commonly used forms of the SARS-CoV-2 spike protein. We show that these proteins form well-behaved stable trimers and are consistently functional in serology assays across multiple protein production lots. url: https://www.ncbi.nlm.nih.gov/pubmed/32504802/ doi: 10.1016/j.pep.2020.105686 id: cord-285647-9tegcrc3 author: Estrada, Ernesto title: Fractional diffusion on the human proteome as an alternative to the multi-organ damage of SARS-CoV-2 date: 2020-08-17 words: 9179.0 sentences: 533.0 pages: flesch: 59.0 cache: ./cache/cord-285647-9tegcrc3.txt txt: ./txt/cord-285647-9tegcrc3.txt summary: By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19. 25, 26 Therefore, we assume here that perturbations produced by SARS-CoV-2 proteins on the human PPI network are propagated by means of diffusive processes. Here, we propose the use of a time-fractional diffusion model on the PPI network of proteins targeted by SARS-CoV-2. We now consider how a perturbation produced by SARS-CoV-2 on a protein mainly expressed in the lungs can be propagated to proteins mainly located in other tissues (see Table S4 in the supplementary material) by a subdiffusive process. Here, we have studied the particular case in which the time-fractional diffusion equation produces a subdiffusive regime, with the use of α = 3/4 in the network of human proteins targeted by SARS-CoV-2. abstract: The coronavirus 2019 (COVID-19) respiratory disease is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which uses the enzyme ACE2 to enter human cells. This disease is characterized by important damage at a multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. However, not every organ in which ACE2 is abundant is affected by SARS-CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus. We consider here diffusive processes through the protein–protein interaction (PPI) network of proteins targeted by SARS-CoV-2 as an alternative route. We found a subdiffusive regime that allows the propagation of virus perturbations through the PPI network at a significant rate. By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32872802/ doi: 10.1063/5.0015626 id: cord-004673-c8qcjve9 author: Faaberg, K. S. title: Membrane association of the C-terminal half of the open reading frame 1a protein of lactate dehydrogenase-elevating virus date: 1996 words: 4647.0 sentences: 220.0 pages: flesch: 55.0 cache: ./cache/cord-004673-c8qcjve9.txt txt: ./txt/cord-004673-c8qcjve9.txt summary: cDNAs encoding ORF 1a protein segments encompassing transmembrane segments 5 to 11 and its amphipathic C-terminal end as well as the N-terminal 80 amino acids of the downstream ORF 1b protein were transcribed and the transcripts in vitro translated in the absence and presence of microsomal membranes. Eisenberg hydrophobic moment analysis of the protein predicted the presence of eleven transmembrane segments in the C-terminal half of the molecule (amino acids 980-1852) that flank the serine protease domain, cDNAs encoding ORF la protein segments encompassing transmembrane segments 5 to 11 and its amphipathic C-terminal end as well as the N-terminal 80 amino acids of the downstream ORF lb protein were transcribed and the transcripts in vitro translated in the absence and presence of microsomal membranes. In the present study we provide strong evidence that the segment of LDV ORF la protein with transmembrane segments 5-11 (see Fig. 1 ) becomes intimately associated with endoplasmic reticulum (ER) membranes during synthesis and that none of its potential N-glycosylation sites becomes glycosylated. abstract: ORF 1a of lactate dehydrogenase-elevating virus, strain P (LDV-P), encodes a protein of 2206 amino acids. Eisenberg hydrophobic moment analysis of the protein predicted the presence of eleven transmembrane segments in the C-terminal half of the molecule (amino acids 980–1852) that flank the serine protease domain. cDNAs encoding ORF 1a protein segments encompassing transmembrane segments 5 to 11 and its amphipathic C-terminal end as well as the N-terminal 80 amino acids of the downstream ORF 1b protein were transcribed and the transcripts in vitro translated in the absence and presence of microsomal membranes. The synthesis of the protein products with putative transmembrane segments was enhanced by the presence of the microsomal membranes and the proteins became membrane associated. When synthesized in the absence of membranes they were recovered in the supernatant upon ultracentrifugation of the translation reaction mixtures, whereas they were recovered in the membrane pellet when synthesized in the presence of membranes. Furthermore, the latter proteins were not released from the membranes by disruption of the membrane vesicles in carbonate buffer, pH 11.5, and large portions of the proteins were resistant to digestion by trypsin, chymotrypsin and proteinase K. No N-glycosylation was observed and only little, if any, processing of the protein by the putative serine protease. The results indicate that the C-terminal half of the ORF 1a protein represents a non-glycosylated integral membrane protein. Potential modes of synthesis and function of the protein are discussed. In addition, the results showed that the synthesis of the ORF 1a protein was generally terminated at its termination codon, but that read-through into the ORF 1b gene occurred with low frequency. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086564/ doi: 10.1007/bf01718835 id: cord-257584-v38tjof3 author: Fahmi, Muhamad title: Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV date: 2020-03-03 words: 2933.0 sentences: 180.0 pages: flesch: 49.0 cache: ./cache/cord-257584-v38tjof3.txt txt: ./txt/cord-257584-v38tjof3.txt summary: Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. This was done using a combination of the phylogenetic tree constructed from the genome sequences and the cluster tree developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The phylogenetic analysis using complete genome sequences showed that 2019-nCoV was the most closely related to BatCoV RaTG13 and belonged to the Sarbecovirus subgenus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus (BAT-SL-CoVZXC21 and BAT-SL-CoVZC45) with the full support of reliability (Fig. 1) . Two (NS7b and NS8) of five nonstructural proteins were specific for 2019-nCoV and its closely related species, BatCoV RaTG13 and Bat-SARS-like coronavirus (BAT-SL-CoVZXC21 and BAT-SL-CoVZC45). abstract: The seventh novel human infecting Betacoronavirus that causes pneumonia (2019 novel coronavirus, 2019-nCoV) originated in Wuhan, China. The evolutionary relationship between 2019-nCoV and the other human respiratory illness-causing coronavirus is not closely related. We sought to characterize the relationship of the translated proteins of 2019-nCoV with other species of Orthocoronavirinae. A phylogenetic tree was constructed from the genome sequences. A cluster tree was developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The combined data were used to characterize the relationship of the translated proteins of 2019-nCoV to other species of Orthocoronavirinae. Our analysis reliably suggests that 2019-nCoV is most closely related to BatCoV RaTG13 and belongs to subgenus Sarbecovirus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus. The phylogenetic profiling cluster of homolog proteins of one annotated 2019-nCoV protein against other genome sequences revealed two clades of ten 2019-nCoV proteins. Clade 1 consisted of a group of conserved proteins in Orthocoronavirinae comprising Orf1ab polyprotein, Nucleocapsid protein, Spike glycoprotein, and Membrane protein. Clade 2 comprised six proteins exclusive to Sarbecovirus and Hibecovirus. Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. Thus, we speculated that knowledge of the functional changes in the NS7b and NS8 proteins during evolution may provide important information to explore the human infective property of 2019-nCoV. url: https://doi.org/10.1016/j.meegid.2020.104272 doi: 10.1016/j.meegid.2020.104272 id: cord-355327-d3gcfepx author: Fan, Samuel W title: Conformational changes in redox pairs of protein structures date: 2009-08-01 words: 9859.0 sentences: 544.0 pages: flesch: 47.0 cache: ./cache/cord-355327-d3gcfepx.txt txt: ./txt/cord-355327-d3gcfepx.txt summary: Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. These groups were: proteins that oxidize disulfides following expulsion of metals such as Zn; proteins that exhibited major reorganization or ''''morphing'''' of portions of the polypeptide backbone in association with disulfide redox-activity; proteins that exhibited order/disorder transitions; and proteins that exhibited changes in quaternary structure. Twenty-nine Redox Pair protein clusters with intermolecular disulfide bonds exhibit changes in quaternary structure upon oxidation/reduction. We were previously aware of two instances where subdomain morphing of proteins has been associated with reversible disulfide reduction: a redox-controlled structural reorganization of the ion channel CLIC1 proposed to regulate its insertion into membranes, 18 and sequential oxidation of the transcription factor OxyR in response to oxidative stress which modulates its quaternary structure and DNA-binding properties. abstract: Disulfides are conventionally viewed as structurally stabilizing elements in proteins but emerging evidence suggests two disulfide subproteomes exist. One group mediates the well known role of structural stabilization. A second redox-active group are best known for their catalytic functions but are increasingly being recognized for their roles in regulation of protein function. Redox-active disulfides are, by their very nature, more susceptible to reduction than structural disulfides; and conversely, the Cys pairs that form them are more susceptible to oxidation. In this study, we searched for potentially redox-active Cys Pairs by scanning the Protein Data Bank for structures of proteins in alternate redox states. The PDB contains over 1134 unique redox pairs of proteins, many of which exhibit conformational differences between alternate redox states. Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. Based on evidence gathered supporting disulfide redox activity, we propose disulfides present in alternate redox states are likely to have physiologically relevant redox activity. url: http://europepmc.org/articles/pmc2776962?pdf=render doi: 10.1002/pro.175 id: cord-001244-qdld7hdc author: Fan, Yue-Nong title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking date: 2014-03-19 words: 6502.0 sentences: 339.0 pages: flesch: 46.0 cache: ./cache/cord-001244-qdld7hdc.txt txt: ./txt/cord-001244-qdld7hdc.txt summary: In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. [59] did not provide a publicly accessible web-server for their method, and hence its practical application value is quite limited, particularly for the broad experimental scientists; (b) The prediction quality can be further enhanced by incorporating some key features into the formulation of NR-drug (nuclear receptor and drug) samples via the general form of pseudo amino acid composition [60] . Prediction of G-protein-coupled receptor classes based on the concept of Chou''s pseudo amino acid composition: An approach from discrete wavelet transform abstract: Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975431/ doi: 10.3390/ijms15034915 id: cord-003020-q69f57el author: Farhadi, Tayebeh title: Computer-aided design of amino acid-based therapeutics: a review date: 2018-05-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: During the last two decades, the pharmaceutical industry has progressed from detecting small molecules to designing biologic-based therapeutics. Amino acid-based drugs are a group of biologic-based therapeutics that can effectively combat the diseases caused by drug resistance or molecular deficiency. Computational techniques play a key role to design and develop the amino acid-based therapeutics such as proteins, peptides and peptidomimetics. In this study, it was attempted to discuss the various elements for computational design of amino acid-based therapeutics. Protein design seeks to identify the properties of amino acid sequences that fold to predetermined structures with desirable structural and functional characteristics. Peptide drugs occupy a middle space between proteins and small molecules and it is hoped that they can target “undruggable” intracellular protein–protein interactions. Peptidomimetics, the compounds that mimic the biologic characteristics of peptides, present refined pharmacokinetic properties compared to the original peptides. Here, the elaborated techniques that are developed to characterize the amino acid sequences consistent with a specific structure and allow protein design are discussed. Moreover, the key principles and recent advances in currently introduced computational techniques for rational peptide design are spotlighted. The most advanced computational techniques developed to design novel peptidomimetics are also summarized. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958949/ doi: 10.2147/dddt.s159767 id: cord-314567-purplsjn author: Fernández-Ponce, Cecilia title: Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells date: 2018-01-04 words: 7978.0 sentences: 382.0 pages: flesch: 41.0 cache: ./cache/cord-314567-purplsjn.txt txt: ./txt/cord-314567-purplsjn.txt summary: HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4 + T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. As studies using the whole virus do not allow for the elucidation of the specific molecular mechanisms in which each protein is implicated, in this work, we focused on a single viral protein, showing that in CD4 + T cells, HCV core protein mostly localizes in the nucleus and specifically in the nucleolus where it is greatly enriched. abstract: Hepatitis C virus core protein is a highly basic viral protein that multimerizes with itself to form the viral capsid. When expressed in CD4(+) T lymphocytes, it can induce modifications in several essential cellular and biological networks. To shed light on the mechanisms underlying the alterations caused by the viral protein, we have analyzed HCV-core subcellular localization and its associations with host proteins in Jurkat T cells. In order to investigate the intracellular localization of Hepatitis C virus core protein, we have used a lentiviral system to transduce Jurkat T cells and subsequently localize the protein using immunoelectron microscopy techniques. We found that in Jurkat T cells, Hepatitis C virus core protein mostly localizes in the nucleus and specifically in the nucleolus. In addition, we performed pull-down assays combined with Mass Spectrometry Analysis, to identify proteins that associate with Hepatitis C virus core in Jurkat T cells. We found proteins such as NOLC1, PP1γ, ILF3, and C1QBP implicated in localization and/or traffic to the nucleolus. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4(+) T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. Thus, in the current work, we show the ultrastructural localization of Hepatitis C virus core and the first profile of HCV core associated proteins in T cells, and we discuss the functions and interconnections of these proteins in molecular networks where relevant biological modifications have been described upon the expression of Hepatitis C virus core protein. Thereby, the current work constitutes a necessary step toward understanding the mechanisms underlying HCV core mediated alterations that had been described in relevant biological processes in CD4(+) T cells. url: https://www.ncbi.nlm.nih.gov/pubmed/29354102/ doi: 10.3389/fmicb.2017.02595 id: cord-313988-3xjnpkqp author: Ferraz, Rosa María title: Insertional protein engineering for analytical molecular sensing date: 2006-04-03 words: 3516.0 sentences: 147.0 pages: flesch: 25.0 cache: ./cache/cord-313988-3xjnpkqp.txt txt: ./txt/cord-313988-3xjnpkqp.txt summary: In this context, insertional protein engineering offers the possibility to develop new devices, efficiently responding to ligand interaction by dramatic conformational changes, in which the specificity and magnitude of the sensing response can be adjusted up to a convenient level for specific analyte species. Among enzyme inhibitors and other few ligand species that activate allosteric biosensors, antibodies have been noted to be specially efficient allosteric effectors [36] and the use of antigenic peptides as receptors in only-protein biosensors would offer appealing tools for the fast molecular diagnosis of infectious diseases [39, 43] . For such a sensor being efficiently responsive, appropriated permissive sites need to be selected permitting proper receptor display and signal transduction, and the whole protein might require further engineering to gain specificity and response range. Among the diversity of sensing strategies based on insertional mutagenesis two protein platforms emerge as the most explored, namely cleavable sensors responding to proteases or their inhibitors, and allosteric, among whose most efficient effectors are antibodies. abstract: The quantitative detection of low analyte concentrations in complex samples is becoming an urgent need in biomedical, food and environmental fields. Biosensors, being hybrid devices composed by a biological receptor and a signal transducer, represent valuable alternatives to non biological analytical instruments because of the high specificity of the biomolecular recognition. The vast range of existing protein ligands enable those macromolecules to be used as efficient receptors to cover a diversity of applications. In addition, appropriate protein engineering approaches enable further improvement of the receptor functioning such as enhancing affinity or specificity in the ligand binding. Recently, several protein-only sensors are being developed, in which either both the receptor and signal transducer are parts of the same protein, or that use the whole cell where the protein is produced as transducer. In both cases, as no further chemical coupling is required, the production process is very convenient. However, protein platforms, being rather rigid, restrict the proper signal transduction that necessarily occurs through ligand-induced conformational changes. In this context, insertional protein engineering offers the possibility to develop new devices, efficiently responding to ligand interaction by dramatic conformational changes, in which the specificity and magnitude of the sensing response can be adjusted up to a convenient level for specific analyte species. In this report we will discuss the major engineering approaches taken for the designing of such instruments as well as the relevant examples of resulting protein-only biosensors. url: https://www.ncbi.nlm.nih.gov/pubmed/16584558/ doi: 10.1186/1475-2859-5-15 id: cord-257465-9yrf7ofy author: Finlay, William J. J. title: Phage Display: A Powerful Technology for the Generation of High-Specificity Affinity Reagents from Alternative Immune Sources date: 2016-05-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Antibodies are critical reagents in many fundamental biochemical methods such as affinity chromatography, enzyme-linked immunosorbent assays (ELISA), flow cytometry, western blotting, immunoprecipitation, and immunohistochemistry techniques. As our understanding of the proteome becomes more complex, demand is rising for rapidly generated antibodies of higher specificity than ever before. It is therefore surprising that few investigators have moved beyond the classical methods of antibody production in their search for new reagents. Despite their long-standing efficacy, recombinant antibody generation technologies such as phage display are still largely the tools of biotechnology companies or research groups with a direct interest in protein engineering. In this chapter, we discuss the inherent limitations of classical polyclonal and monoclonal antibody generation and highlight an attractive alternative: generating high-specificity, high-affinity recombinant antibodies from alternative immune sources such as chickens, via phage display. url: https://www.ncbi.nlm.nih.gov/pubmed/27730550/ doi: 10.1007/978-1-4939-6412-3_6 id: cord-330852-n7j0c4ne author: Fischer, Wolfgang B. title: Mechanism of Function of Viral Channel Proteins and Implications for Drug Development date: 2012-02-23 words: 23680.0 sentences: 1178.0 pages: flesch: 53.0 cache: ./cache/cord-330852-n7j0c4ne.txt txt: ./txt/cord-330852-n7j0c4ne.txt summary: By adding data from functional studies like Cys scanning and electrophysiological measurements as mentioned as well as computational modeling data (Sansom and Kerr, 1993; Sansom et al., 1997; Zhong et al., 1998) , an approximate structural model of the tetrameric assembly of the TMDs of M2 with the histidines and tryptophans as important pore lining residues has been generated. Amiloride derivatives block ion channel activity and enhancement of virus-like particle budding caused by HIV-1 protein Vpu Backbone structure of the amantadine-blocked trans-membrane domain M2 protein channel from influenza A virus Molecular dynamics investigation of membrane-bound bundles of the channel-forming transmembrane domain of viral protein U from the Human Immunodeficiency Virus HIV-1 Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes Three-dimensional structure of the channel-forming trans-membrane domain of virus protein "u" (Vpu) from HIV-1 abstract: Viral channel-forming proteins comprise a class of viral proteins which, similar to their host companions, are made to alter electrochemical or substrate gradients across lipid membranes. These proteins are active during all stages of the cellular life cycle of viruses. An increasing number of proteins are identified as channel proteins, but the precise role in the viral life cycle is yet unknown for the majority of them. This review presents an overview about these proteins with an emphasis on those with available structural information. A concept is introduced which aligns the transmembrane domains of viral channel proteins with those of host channels and toxins to give insights into the mechanism of function of the viral proteins from potential sequence identities. A summary of to date investigations on drugs targeting these proteins is given and discussed in respect of their mode of action in vivo. url: https://doi.org/10.1016/b978-0-12-394305-7.00006-9 doi: 10.1016/b978-0-12-394305-7.00006-9 id: cord-339091-3xk2w0d2 author: Flower, Darren R title: Computer aided selection of candidate vaccine antigens date: 2010-11-03 words: 10669.0 sentences: 558.0 pages: flesch: 40.0 cache: ./cache/cord-339091-3xk2w0d2.txt txt: ./txt/cord-339091-3xk2w0d2.txt summary: The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. Initially, the pathogenic genome is scanned for "open reading frames" or ORFs. Once all ORFs have been identified, proteins are selected on the basis that they will be accessible to immune system surveillance, usually using some form of informatic-based prediction methodology or, more likely, set of methdologies. We shall below examine three key approaches: subcellular location prediction, sequence similarity, and empirical statistical approaches, typified by VaxiJen. For a protein to be accessible to surveillance by the immune system, it is often assumed to be physically external to the microbial organism or at least present on its surface rather than being sequestered away far from the roving eye of the immune system. abstract: Immunoinformatics is an emergent branch of informatics science that long ago pullulated from the tree of knowledge that is bioinformatics. It is a discipline which applies informatic techniques to problems of the immune system. To a great extent, immunoinformatics is typified by epitope prediction methods. It has found disappointingly limited use in the design and discovery of new vaccines, which is an area where proper computational support is generally lacking. Most extant vaccines are not based around isolated epitopes but rather correspond to chemically-treated or attenuated whole pathogens or correspond to individual proteins extract from whole pathogens or correspond to complex carbohydrate. In this chapter we attempt to review what progress there has been in an as-yet-underexplored area of immunoinformatics: the computational discovery of whole protein antigens. The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. We begin our review by placing antigen prediction firmly into context, exploring the role of reverse vaccinology in the design and discovery of vaccines. We also highlight several competing yet ultimately complementary methodological approaches: sub-cellular location prediction, identifying antigens using sequence similarity, and the use of sophisticated statistical approaches for predicting the probability of antigen characteristics. We end by exploring how a systems immunomics approach to the prediction of immunogenicity would prove helpful in the prediction of antigens. url: https://doi.org/10.1186/1745-7580-6-s2-s1 doi: 10.1186/1745-7580-6-s2-s1 id: cord-016594-lj0us1dq author: Flower, Darren R. title: Identification of Candidate Vaccine Antigens In Silico date: 2012-09-28 words: 12570.0 sentences: 653.0 pages: flesch: 37.0 cache: ./cache/cord-016594-lj0us1dq.txt txt: ./txt/cord-016594-lj0us1dq.txt summary: In the wider context of the experimental discovery of vaccine antigens, with particular reference to reverse vaccinology, this chapter adumbrates the principal computational approaches currently deployed in the hunt for novel antigens: genome-level prediction of antigens, antigen identification through the use of protein sequence alignment-based approaches, antigen detection through the use of subcellular location prediction, and the use of alignment-independent approaches to antigen discovery. When looking at a reverse vaccinology process, the discovery of candidate subunit vaccines begins with a microbial genome, perhaps newly sequence, progresses through an extensive computational stage, ultimately to deliver a shortlist of antigens which can be validated through subsequent laboratory examination. Conventional empirical, experimental, laboratory-based microbiological ways to identify putative candidate antigens require cultivation of target pathogenic micro-organisms, followed by teasing out their component proteins, analysis in a series of in-vitro and in-vivo assays, animal models and with the ultimate objective of isolating one or two proteins displaying protective immunity. abstract: The identification of immunogenic whole-protein antigens is fundamental to the successful discovery of candidate subunit vaccines and their rapid, effective, and efficient transformation into clinically useful, commercially successful vaccine formulations. In the wider context of the experimental discovery of vaccine antigens, with particular reference to reverse vaccinology, this chapter adumbrates the principal computational approaches currently deployed in the hunt for novel antigens: genome-level prediction of antigens, antigen identification through the use of protein sequence alignment-based approaches, antigen detection through the use of subcellular location prediction, and the use of alignment-independent approaches to antigen discovery. Reference is also made to the recent emergence of various expert systems for protein antigen identification. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120937/ doi: 10.1007/978-1-4614-5070-2_3 id: cord-320790-ley91488 author: Fogg, M. J. title: Application of the use of high‐throughput technologies to the determination of protein structures of bacterial and viral pathogens date: 2006-10-04 words: 7066.0 sentences: 320.0 pages: flesch: 47.0 cache: ./cache/cord-320790-ley91488.txt txt: ./txt/cord-320790-ley91488.txt summary: Here the impact of several technologies on the structural determination of proteins from human pathogens is illustrated with selected examples, including the parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens. Here the impact of several technologies on the structural determination of proteins from human pathogens is illustrated with selected examples, including the parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens. Further development and uptake of these methodologies (see Aricescu, Assenberg et al., 2006; Aricescu, Lu et al., 2006) is likely to have a major impact on the study of difficult viral targets, as indicated by preliminary results for EBV proteins, where insect-cell expression yielded soluble protein for 50% of the proteins tested (Tarbouriech et al., 2006) Here we illustrate the impact of a number of particular SPINE-based technologies on the structure determination of pathogen targets, namely (i) multiple-construct design for a single target, (ii) optimization of protein solubility, (iii) eukaryotic expression systems, (iv) standardized refolding protocols, (v) surface engineering and (vi) other biophysical characterization. abstract: The Structural Proteomics In Europe (SPINE) programme is aimed at the development and implementation of high‐throughput technologies for the efficient structure determination of proteins of biomedical importance, such as those of bacterial and viral pathogens linked to human health. Despite the challenging nature of some of these targets, 175 novel pathogen protein structures (∼220 including complexes) have been determined to date. Here the impact of several technologies on the structural determination of proteins from human pathogens is illustrated with selected examples, including the parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens. url: https://www.ncbi.nlm.nih.gov/pubmed/17001096/ doi: 10.1107/s0907444906030915 id: cord-277293-eo3bei9x author: Fondong, Vincent N. title: Geminivirus protein structure and function date: 2013-04-25 words: 10141.0 sentences: 507.0 pages: flesch: 47.0 cache: ./cache/cord-277293-eo3bei9x.txt txt: ./txt/cord-277293-eo3bei9x.txt summary: The replication-associated protein (Rep) encoded by the AC1 ORF (also called AL1) in bipartite geminiviruses and by C1 (also called L1) in monopartite geminiviruses (except mastreviruses) is conserved in sequence, position and function (Hanley-Bowdoin et al., 2004) and is expressed under the control of a bidirectional core promoter in the IR (Hanley-Bowdoin et al., 1999) . SINAC1 levels were shown to be higher in ToLCV-infected cells, suggesting that NAC1 is involved in viral DNA replication (Selth et al., 2005) , possibly through an interaction with REn. Recently, the Tomato leaf curl Kerala virus REn was shown to interact with Rep and enhance the Repmediated ATPase activity (Pasumarthy et al., 2010) , thus confirming a role for REn in viral DNA replication. abstract: Geminiviruses are a family of plant viruses that cause economically important plant diseases worldwide. These viruses have circular single‐stranded DNA genomes and four to eight genes that are expressed from both strands of the double‐stranded DNA replicative intermediate. The transcription of these genes occurs under the control of two bidirectional promoters and one monodirectional promoter. The viral proteins function to facilitate virus replication, virus movement, the assembly of virus‐specific nucleoprotein particles, vector transmission and to counteract plant host defence responses. Recent research findings have provided new insights into the structure and function of these proteins and have identified numerous host interacting partners. Most of the viral proteins have been shown to be multifunctional, participating in multiple events during the infection cycle and have, indeed, evolved coordinated interactions with host proteins to ensure a successful infection. Here, an up‐to‐date review of viral protein structure and function is presented, and some areas requiring further research are identified. url: https://www.ncbi.nlm.nih.gov/pubmed/23615043/ doi: 10.1111/mpp.12032 id: cord-259237-aty0vrat author: Frabutt, Dylan A. title: Arms Race between Enveloped Viruses and the Host ERAD Machinery date: 2016-09-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during the infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed to potentiate or inhibit viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells. url: https://www.ncbi.nlm.nih.gov/pubmed/27657106/ doi: 10.3390/v8090255 id: cord-252304-lwiulri7 author: Fragnoud, Romain title: Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue date: 2015-11-14 words: 8324.0 sentences: 433.0 pages: flesch: 46.0 cache: ./cache/cord-252304-lwiulri7.txt txt: ./txt/cord-252304-lwiulri7.txt summary: ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. CONCLUSION: A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. Fig. 2 Ingenuity Pathway Analysis for host proteins identified in the viral-enriched plasma fraction of patients with dengue. To validate the mass spectrometry data, the levels of selected host proteins were assessed by quantitative ELISA both in the virus-enriched fraction and in individual plasma samples from DF or SD patients. In this regard, further studies are required to assess the prognostic value of host proteins associated with inflammation, complement cascade and coagulation for disease severity by analysis of additional biological samples from patients infected with DV. abstract: BACKGROUND: Dengue is the most widespread mosquito-borne viral disease of public health concern. In some patients, endothelial cell and platelet dysfunction lead to life-threatening hemorrhagic dengue fever or dengue shock syndrome. Prognostication of disease severity is urgently required to improve patient management. The pathogenesis of severe dengue has not been fully elucidated, and the role of host proteins associated with viral particles has received little exploration. METHODS: The proteomes of virion-enriched fractions purified from plasma pools of patients with dengue fever or severe dengue were compared. Virions were purified by ultracentrifugation combined with a water-insoluble polyelectrolyte-based technique. Following in-gel hydrolysis, peptides were analyzed by nano-liquid chromatography coupled to ion trap mass spectrometry and identified using data libraries. RESULTS: Both dengue fever and severe dengue viral-enriched fractions contained identifiable viral envelope proteins and host cellular proteins. Canonical pathway analysis revealed the identified host proteins are mainly involved in the coagulation cascade, complement pathway or acute phase response signaling pathway. Some host proteins were over- or under-represented in plasma from patients with severe dengue compared to patients with dengue fever. ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. Among 22 host proteins tested, two could differentiate between dengue fever and severe dengue in two independent cohorts (olfactomedin-4: area under the curve (AUC), 0.958; and platelet factor-4: AUC, 0.836). CONCLUSION: A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. The impact of these host proteins on pathogenicity and disease outcome are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1271-7) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1186/s12879-015-1271-7 doi: 10.1186/s12879-015-1271-7 id: cord-016448-7imgztwe author: Frishman, D. title: Protein-protein interactions: analysis and prediction date: 2009-10-01 words: 18354.0 sentences: 912.0 pages: flesch: 39.0 cache: ./cache/cord-016448-7imgztwe.txt txt: ./txt/cord-016448-7imgztwe.txt summary: In general, investigating the topology of protein interaction, metabolic, signaling, and transcriptional networks allows researchers to reveal the fundamental principles of molecular organization of the cell and to interpret genome data in the context of large-scale experiments. The basic principle is fairly simple and rests implicitly on a multigraph representation: several interaction networks to be integrated, each resulting from a specific experimental or predictive method, are defined over the same set of proteins. This software provides functionalities for (i) generating biological networks, either manually or by importing interaction data from various sources, (ii) filtering interactions, (iii) displaying networks using graph layout algorithms, (iv) integrating and displaying additional information like gene expression data, and (v) performing analyses on networks, for instance, by calculating topological network properties or by identifying functional modules. The evidence can be derived from literature mining, functional associations based on Gene Ontology annotations, co-occurrence of transcriptional motifs, correlation of expression data, sequence similarity, common protein domains, shared metabolic pathway membership, and protein-protein interactions. abstract: Proteins represent the tools and appliances of the cell — they assemble into larger structural elements, catalyze the biochemical reactions of metabolism, transmit signals, move cargo across membrane boundaries and carry out many other tasks. For most of these functions proteins cannot act in isolation but require close cooperation with other proteins to accomplish their task. Often, this collaborative action implies physical interaction of the proteins involved. Accordingly, experimental detection, in silico prediction and computational analysis of protein-protein interactions (PPI) have attracted great attention in the quest for discovering functional links among proteins and deciphering the complex networks of the cell. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120725/ doi: 10.1007/978-3-211-75123-7_17 id: cord-326015-ky4y2xjt author: Füllekrug, Joachim title: Protein sorting in the Golgi complex date: 1998-08-14 words: 3937.0 sentences: 202.0 pages: flesch: 50.0 cache: ./cache/cord-326015-ky4y2xjt.txt txt: ./txt/cord-326015-ky4y2xjt.txt summary: In this review, we will discuss sorting of resident proteins in the Golgi complex mainly in the context of cisternal maturation [1, 2] . An essential feature of this maturation model is the prediction that Golgi resident proteins are more concentrated in retrograde vesicles than they are in the cisternae of the Golgi apparatus. This shows that Golgi resident enzymes do form gradients across the pathway and that these are unique to the particular protein. The surprising ¢nding that the membrane spanning domain (MSD) of Golgi residents su¤ced to localise reporter molecules to the appropriate part of the pathway suggested that this domain harboured important sorting information (for review, see [22] ). As this form of coatomer is found on Golgi associated transport vesicles [50] , COP I vesicles constitute RTCs. The presence of K(X)KXX or related signals on membrane proteins other than ER residents allows for the possibility that this motif also acts later in the pathway. abstract: Even after one hundred years, the Golgi apparatus remains a major challenge in the field of Cell Biology. This is particularly true in terms of transport and of protein sorting. For example, the question how cargo proteins are transported through this organelle is still a matter of debate. Emphasis has been put on the role of anterograde and retrograde transport vesicles. These have been proposed to carry cargo from cisterna to cisterna and to recycle components needed for further rounds of transport. Alternatively, anterograde movement of cargo takes place in cisternal membranes rather than transport vesicles. These membranes assemble and mature in a cis to trans direction. In this case, retrograde transport vesicles need to recycle all components of the Golgi apparatus and this demands a highly dynamic and efficient sorting machinery. Here we will discuss possible mechanisms for protein sorting in the context of cisternal maturation and propose that a common mechanism is sufficient to explain both transport of cargo and sorting of resident proteins. url: https://www.ncbi.nlm.nih.gov/pubmed/9714747/ doi: 10.1016/s0167-4889(98)00048-2 id: cord-271091-ffn59sgf author: Galao, Rui P title: Saccharomyces cerevisiae: a versatile eukaryotic system in virology date: 2007-10-10 words: 6539.0 sentences: 318.0 pages: flesch: 42.0 cache: ./cache/cord-271091-ffn59sgf.txt txt: ./txt/cord-271091-ffn59sgf.txt summary: These include the analysis of the function of individual proteins from important pathogenic viruses, the elucidation of key processes in viral replication through the development of systems that allow the replication of higher eukayotic viruses in yeast, and the use of yeast in antiviral drug development and vaccine production. Although the expression of viral proteins in yeast not always necessarily reflects their role in higher eukaryotes, here we selected some examples in which the analysis in yeast of their effect on highly conserved cellular processes such as cell cycle control, apoptosis or mRNA degradation have contributed to the current understanding of the pathogenesis of important viral pathogens such as HIV-1 and HCV. The identification of the host factors involved in viral RNA replication is a priority area of research in virology because it can provide new targets for antiviral drug development. abstract: The yeast Saccharomyces cerevisiae is a well-established model system for understanding fundamental cellular processes relevant to higher eukaryotic organisms. Less known is its value for virus research, an area in which Saccharomyces cerevisiae has proven to be very fruitful as well. The present review will discuss the main achievements of yeast-based studies in basic and applied virus research. These include the analysis of the function of individual proteins from important pathogenic viruses, the elucidation of key processes in viral replication through the development of systems that allow the replication of higher eukayotic viruses in yeast, and the use of yeast in antiviral drug development and vaccine production. url: https://www.ncbi.nlm.nih.gov/pubmed/17927824/ doi: 10.1186/1475-2859-6-32 id: cord-260949-w2xuf15h author: Galluzzi, Lorenzo title: Viral Control of Mitochondrial Apoptosis date: 2008-05-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus. url: https://doi.org/10.1371/journal.ppat.1000018 doi: 10.1371/journal.ppat.1000018 id: cord-302009-oqc21fah author: Geng, Xindu title: Protein folding liquid chromatography and its recent developments() date: 2007-04-15 words: 6669.0 sentences: 334.0 pages: flesch: 49.0 cache: ./cache/cord-302009-oqc21fah.txt txt: ./txt/cord-302009-oqc21fah.txt summary: Protein folding liquid chromatography (PFLC) is a new method developed in recent years, and it is widely used in molecular biology and biotechnology. When it is used in protein folding, the bioactivity recovery increases, the folded protein can be easily separated from misfolded forms, protein concentration after refolding is relatively high, and it is easy to scale up and automate, therefore it is regarded as an efficient, and close to ideal refolding method [1, 2] . In addition, by continuously changing the components of the mobile phase, different proteins can be separated with suitable folding conditions to refold and simultaneously purify in only one chromatographic run. Chaperone solvent plug SEC proposed by Liu and Chang [16] could obviously reduce precipitates formed before denatured protein entered the top of the column, and relatively high mass recovery was obtained. [57] recently proposed a relatively versatile refolding method using IEC with a silica-based weak cation exchanger, very high mass and bioactivity recoveries were obtained for denatured lysozyme. abstract: The ultimate goal of proteomics is to identify biologically active proteins and to produce them using biotechnology tools such as bacterial hosts. However, proteins produced by Escherichia coli must be refolded to their native state. Protein folding liquid chromatography (PFLC) is a new method developed in recent years, and it is widely used in molecular biology and biotechnology. In this paper, the new method, PFLC is introduced and its recent development is reviewed. In addition the paper includes definitions, advantages, principles, applications for both laboratory and large scales, apparatus, and effecting factors of PFLC. In addition, the role of this method in the future is examined. url: https://www.ncbi.nlm.nih.gov/pubmed/17116432/ doi: 10.1016/j.jchromb.2006.10.068 id: cord-298736-9bvyp21d author: Gerold, Gisa title: Decoding protein networks during virus entry by quantitative proteomics date: 2016-06-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins. Particularly, protein–protein interactions between viral surface proteins and host proteins as well as secondary host protein–protein interactions play a pivotal role in coordinating virus binding and uptake. These interactions are dynamic and frequently involve multiprotein complexes. In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material. As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox. Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques. We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future. url: https://api.elsevier.com/content/article/pii/S0168170215300617 doi: 10.1016/j.virusres.2015.09.006 id: cord-280360-rh37d5wc author: Gibson, David S. title: Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis – Proteomic patterns of joint inflammation in early stage disease date: 2009-05-02 words: 8297.0 sentences: 388.0 pages: flesch: 41.0 cache: ./cache/cord-280360-rh37d5wc.txt txt: ./txt/cord-280360-rh37d5wc.txt summary: title: Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis – Proteomic patterns of joint inflammation in early stage disease Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis -Proteomic patterns of joint inflammation in early stage disease 1 We initially performed a study of the proteins expressed within synovial fluid and plasma in early JIA in order to discover novel biomarkers which distinguish between local and systemic components of joint inflammation in arthritis. The simultaneous analysis of individual paired plasma and synovial fluids from ten patients ( Table 1 , study group A) was used to initially isolate joint-specific protein expression profiles, without introducing bias from inter-individual differences. A number of proteins with consistent synovial and plasma ''specific'' expression patterns are highlighted and quantified to demonstrate the ability to reliably differentiate molecular fingerprints of local and systemic disease across patient groups by this gel based approach. abstract: Synovial fluid is a potential source of novel biomarkers for many arthritic disorders involving joint inflammation, including juvenile idiopathic arthritis. We first compared the distinctive protein ‘fingerprints’ of local inflammation in synovial fluid with systemic profiles within matched plasma samples. The synovial fluid proteome at the time of joint inflammation was then evaluated across clinical subgroups to identify early disease associated proteins. We measured the synovial fluid and plasma proteomes using the two-dimensional fluorescence difference gel electrophoresis approach. Image analysis software was used to highlight the expression levels of joint and subgroup associated proteins across the study cohort (n = 32). A defined subset of 30 proteins had statistically significant differences (p < 0.05) between sample types such that synovial fluid could be differentiated from plasma. Furthermore distinctive synovial proteome expression patterns segregate patient subgroups. Protein expression patterns localized in the chronically inflamed joint therefore have the potential to identify patients more likely to suffer disease which will spread from a single joint to multiple joints. The proteins identified could act as criteria to prevent disease extension by more aggressive therapeutic intervention directed at an earlier stage than is currently possible. url: https://www.ncbi.nlm.nih.gov/pubmed/19367684/ doi: 10.1016/j.jprot.2009.01.022 id: cord-018969-0zrnfaad author: Giese, Matthias title: Types of Recombinant Vaccines date: 2015-09-24 words: 14221.0 sentences: 811.0 pages: flesch: 48.0 cache: ./cache/cord-018969-0zrnfaad.txt txt: ./txt/cord-018969-0zrnfaad.txt summary: New vaccines and vaccination strategies are being developed including the use of attenuated live mycobacteria, recombinant microorganisms, and subunits, prime-boost strategies based on the successive administration of a certain mycobacterial antigen under two different vaccine vectors, and DNA vaccines [ 1 ] . However, several animal models have been developed to study the pathogenesis of Shigella , the resulting immune response against Shigella antigens, and the protection efficacy of candidate vaccines against shigellosis: [ 31 ] . The GAS M protein is the major protective antigen and an ideal target for vaccine development; however it contains heart tissue cross-reactive epitopes particularly in the conserved region [ 98 ] . Immunization of mice with a C-region peptide GAS vaccine candidate called J8 conjugated to the carrier protein diphtheria toxoid (dT) and co-delivery with an appropriate adjuvant led to protection against systemic and mucosal GAS infection [ 104 ] (Fig. 9.29 ). abstract: The original scientific strategy behind vaccinology has historically been to “isolate, inactivate, and inject,” first invoked by Louis Pasteur. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123991/ doi: 10.1007/978-3-319-25832-4_9 id: cord-260345-ugd8kkor author: Giles, Ian G. title: A compendium of reviews in biochemistry and molecular biology published in the first half of 1992 date: 1992-12-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract 1. 1. A compendium of reviews and mini-reviews in Biochemistry and Molecular Biology published in the first half of 1992 is presented. In all 499 titles are listed from 95 different publications. 2. 2. This compendium presents the references by Journal Name. Keywords have been included with each reference to increase the value of the collection. Keyword and author cross-reference indexes are not included but are available in the electronic database from which this version was constructed. Should anyone wish to have this information in electronic form it can be distributed on MS-DOS formatted flopppy disks in either Reference Manager or Medline format. The author should be contacted for details of the number of preformatted floppy disks required. url: https://www.sciencedirect.com/science/article/pii/0020711X92902837 doi: 10.1016/0020-711x(92)90283-7 id: cord-346916-jj4l9ydl author: Girardi, Erika title: Roadblocks and fast tracks: How RNA binding proteins affect the viral RNA journey in the cell date: 2020-08-23 words: 13119.0 sentences: 728.0 pages: flesch: 45.0 cache: ./cache/cord-346916-jj4l9ydl.txt txt: ./txt/cord-346916-jj4l9ydl.txt summary: Moreover, despite the molecular mimicry set by RNA viruses to resemble cellular mRNAs and escape host recognition, the viral nucleic acid still needs to embark on a long journey through a hostile cell environment and must overcome the obstacles put in place by the host antiviral system in order to be translated and replicated. Another example, is the zinc-finger antiviral protein (ZAP), which binds vRNAs containing a ZAP response element (ZRE) and induces RNA degradation via interaction of its N-terminal domain with host decay machinery mediated [75] (Fig. 1 ). In fact, IRES elements present in the genome of different families of RNA viruses lack overall conserved features [146, 147] .The classification of viral IRESs in four types stems from their structural organization, their respective dependence on sets of translation initiation factors, and whether they use scanning or instead directly recruit ribosomes to the start codon [148] (Fig. 2) . abstract: As obligate intracellular parasites with limited coding capacity, RNA viruses rely on host cells to complete their multiplication cycle. Viral RNAs (vRNAs) are central to infection. They carry all the necessary information for a virus to synthesize its proteins, replicate and spread and could also play essential non-coding roles. Regardless of its origin or tropism, vRNA has by definition evolved in the presence of host RNA Binding Proteins (RBPs), which resulted in intricate and complicated interactions with these factors. While on one hand some host RBPs recognize vRNA as non-self and mobilize host antiviral defenses, vRNA must also co-opt other host RBPs to promote viral infection. Focusing on pathogenic RNA viruses, we will review important scenarios of RBP-vRNA interactions during which host RBPs recognize, modify or degrade vRNAs. We will then focus on how vRNA hijacks the largest ribonucleoprotein complex (RNP) in the cell, the ribosome, to selectively promote the synthesis of its proteins. We will finally reflect on how novel technologies are helping in deepening our understanding of vRNA-host RBPs interactions, which can be ultimately leveraged to combat everlasting viral threats. url: https://api.elsevier.com/content/article/pii/S1084952120300914 doi: 10.1016/j.semcdb.2020.08.006 id: cord-350286-n7ylgqfu author: Giri, Rajanish title: When Darkness Becomes a Ray of Light in the Dark Times: Understanding the COVID-19 via the Comparative Analysis of the Dark Proteomes of SARS-CoV-2, Human SARS and Bat SARS-Like Coronaviruses date: 2020-04-03 words: 15827.0 sentences: 874.0 pages: flesch: 56.0 cache: ./cache/cord-350286-n7ylgqfu.txt txt: ./txt/cord-350286-n7ylgqfu.txt summary: The results of this analysis are summarized in Table 2 , which clearly shows that most of the SARS-CoV-2 proteins contain at least one MoRF, indicating that disorder does play an important role in the functionality of these viral proteins. As it follows from Figure 3 , these cleavage sites are located within the IDPRs. In Human SARS CoV S protein, fusion peptide (residues 770-788) is located within a flexible region, is characterized by the mean disorder score of 0.232±0.053. Global analysis of intrinsic disorder in the replicase polyprotein 1ab Table 3 represents the PPID mean scores of 15 non-structural proteins (Nsps) derived from the Replicase polyprotein 1ab in SARS-CoV-2, Human SARS CoV, and Bat CoV. Similar to many other non-structural proteins of coronaviruses, Nsp15s from SARS-CoV-2, Human SARS, and Bat CoV are predicted to possess multiple flexible regions but contain virtually no IDPRs (see Figures 32A, 32B, and 32C) . abstract: Recently emerged coronavirus designated as SARS-CoV-2 (also known as 2019 novel coronavirus (2019-nCoV) or Wuhan coronavirus) is a causative agent of coronavirus disease 2019 (COVID-19), which is rapidly spreading throughout the world now. More than 9,00,000 cases of SARS-CoV-2 infection and more than 47,000 COVID-19-associated mortalities have been reported worldwide till the writing of this article, and these numbers are increasing every passing hour. World Health Organization (WHO) has declared the SARS-CoV-2 spread as a global public health emergency and admitted that the COVID-19 is a pandemic now. The multiple sequence alignment data correlated with the already published reports on the SARS-CoV-2 evolution and indicated that this virus is closely related to the bat Severe Acute Respiratory Syndrome-like coronavirus (bat SARS-like CoV) and the well-studied Human SARS coronavirus (SARS CoV). The disordered regions in viral proteins are associated with the viral infectivity and pathogenicity. Therefore, in this study, we have exploited a set of complementary computational approaches to examine the dark proteomes of SARS-CoV-2, bat SARS-like, and human SARS CoVs by analysing the prevalence of intrinsic disorder in their proteins. According to our findings, SARS-CoV-2 proteome contains very significant levels of structural order. In fact, except for Nucleocapsid, Nsp8, and ORF6, the vast majority of SARS-CoV-2 proteins are mostly ordered proteins containing less intrinsically disordered protein regions (IDPRs). However, IDPRs found in SARS-CoV-2 proteins are functionally important. For example, cleavage sites in its replicase 1ab polyprotein are found to be highly disordered, and almost all SARS-CoV-2 proteins were shown to contain molecular recognition features (MoRFs), which are intrinsic disorder-based protein-protein interaction sites that are commonly utilized by proteins for interaction with specific partners. The results of our extensive investigation of the dark side of the SARS-CoV-2 proteome will have important implications for the structural and non-structural biology of SARS or SARS-like coronaviruses. Significance The infection caused by a novel coronavirus (SARS-CoV-2) that causes severe respiratory disease with pneumonia-like symptoms in humans is responsible for the current COVID-19 pandemic. No in-depth information on structures and functions of SARS-CoV-2 proteins is currently available in the public domain, and no effective anti-viral drugs and/or vaccines are designed for the treatment of this infection. Our study provides the first comparative analysis of the order- and disorder-based features of the SARS-CoV-2 proteome relative to human SARS and bat CoV that may be useful for structure-based drug discovery. url: https://doi.org/10.1101/2020.03.13.990598 doi: 10.1101/2020.03.13.990598 id: cord-005034-wyipzwo4 author: Gleeson, Paul A. title: Targeting of proteins to the Golgi apparatus date: 1994 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Golgi apparatus maintains a highly organized structure in spite of the intense membrane traffic which flows into and out of this organelle. Resident Golgi proteins must have localization signals to ensure that they are targeted to the correct Golgi compartment and not swept further along the secretory pathway. There are a number of distinct groups of Golgi membrane proteins, including glycosyltransferases, recyclingtrans-Golgi network proteins, peripheral membrane proteins, receptors and viral glycoproteins. Recent studies indicate that there are a number of different Golgi localization signals and mechanisms for retaining proteins to the Golgi apparatus. This review focuses on the current knowledge in this field. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088089/ doi: 10.1007/bf00731273 id: cord-273019-hbpfz8rt author: Glingston, R. Sahaya title: Organelle dynamics and viral infections: at cross roads date: 2018-06-25 words: 9513.0 sentences: 486.0 pages: flesch: 35.0 cache: ./cache/cord-273019-hbpfz8rt.txt txt: ./txt/cord-273019-hbpfz8rt.txt summary: Studies on the herpes simplex virus-1 (HSV-1) infection on Vero, BHK-21 and PtK 2 cells reported transportation of viral tegument-capsid by dynein to the cytoplasmic side of NPC [22, 23] . In order to construct these compartments, viruses alter host''s fatty acid metabolism, induce rearrangement of the membrane constituents and also recruit cellular machinery to produce proteins essential for its replication [59, 60] . Upregulation of mitophagy and degradation of the mitochondrial antiviral signalling protein (MAVS) in order to attenuate the antiviral immune response in non-small cell lung cancer (NSCLC) cells was reported upon measles virus infection [83] . The expression of matrix protein (M) of human parainfluenza virus type 3 (HPIV3) in HEK293T and HeLa cells was reported to induce mitophagy resulting in the suppression of type1 interferon response [84] . Many viruses or viral proteins are reported to localize to peroxisomes and/or exploit their functions to facilitate their replication in the host cells [108] . abstract: Viruses are obligate intracellular parasites of the host cells. A commonly accepted view is the requirement of internal membranous structures for various aspects of viral life cycle. Organelles enable favourable intracellular environment for several viruses. However, studies reporting organelle dynamics upon viral infections are scant. In this review, we aim to summarize and highlight modulations caused to various organelles upon viral infection or expression of its proteins. url: https://api.elsevier.com/content/article/pii/S1286457918301412 doi: 10.1016/j.micinf.2018.06.002 id: cord-256316-1odgm6hm author: Godet, Murielle title: TGEV corona virus ORF4 encodes a membrane protein that is incorporated into virions date: 1992-06-30 words: 5433.0 sentences: 269.0 pages: flesch: 48.0 cache: ./cache/cord-256316-1odgm6hm.txt txt: ./txt/cord-256316-1odgm6hm.txt summary: Several lines of evidence lend support to the view that a gene encoding an SM-like protein is a common feature of the coronavirus genomes: (i) an ORF predicting a polypeptide with striking similarities to TGEV ORF4 was identified in the genome sequence of each of the 5 coronaviruses examined (Fig. 9 ) and the fact that TGEV SM was recognized by anti-FIPV antibodies argues for the presence of a related gene also in feline infectious peritonitis virus genome; (ii) the product expressed from the relevant MHV, BCV, and IBV ORFs was reported to have properties of a transmembrane polypeptide (Leibowitz et a/., 1988; Smith et al., 1990; Abraham et a/., 1990) ; and (iii) although expressed through a mono-, di-, or tricistronic mRNA (Abraham et a/., 1990; Budzilowicz and Weiss, 1987; Liu et al., 1991 ) the assumed SM-encoding genes are all located upstream and adjacent to the M protein gene. abstract: Abstract The coding potential of the open reading frame ORF4 (82 amino acids) of transmissible gastroenteritis virus (TGEV) has been confirmed by expression using a baculovirus vector. Five monoclonal antibodies (MAbs) raised against the 10K recombinant product immunoprecipitated a polypeptide of a similar size in TGEV-infected cells. Immunofluorescence assays performed both on insect and mammalian cells revealed that ORF4 was a membrane-associated protein, a finding consistent with the prediction of a membrane-spanning segment in ORF4 sequence. Two epitopes were localized within the last 21 C-terminal residues of the sequence through peptide scanning and analysis of the reactivity of a truncated ORF4 recombinant protein. Since the relevant MAbs were found to induce a cell surface fluorescence, these data suggest that ORF4 may be an integral membrane protein having a Cexo-Nendo orientation. Anti-ORF4 MAbs were also used to show that ORF4 polypeptide may be detected in TGEV virion preparations, with an estimated number of 20 molecules incorporated per particle. Comparison of amino acid sequence data provided strong evidence that other coronaviruses encode a polypeptide homologous to TGEV ORF4. Our results led us to propose that ORF4 represents a novel minor structural polypeptide, tentatively designated SM (small membrane protein). url: https://www.ncbi.nlm.nih.gov/pubmed/1316677/ doi: 10.1016/0042-6822(92)90521-p id: cord-315570-khm1veuv author: González-Mora, Alejandro title: Bacteriophage-Based Vaccines: A Potent Approach for Antigen Delivery date: 2020-09-04 words: 9969.0 sentences: 455.0 pages: flesch: 40.0 cache: ./cache/cord-315570-khm1veuv.txt txt: ./txt/cord-315570-khm1veuv.txt summary: This system relies on bacteriophages displaying proteins or peptides with high affinity to antigen-presenting cells or the antigen itself and at the same time they carry on their genome an eukaryotic expression cassette encoding a specific antigen with the final aim of increasing the immune response by combining both effects (Figure 1 ) [6] . developed a double-hybrid filamentous bacteriophage fd co-displaying peptides recognized by the Major Histocompatibility Complex (MHC) class I and MHC class II cell surface receptors and epitopes from the antigen MAGE aiming to enhance the anti-tumor immune activity based on CTL responses [62] . Thus, the adjuvant-like effect exhibited by phages in various vaccination studies along with their capacity to effectively present peptides or proteins to the immune system leading to the activation of cellular and humoral immune responses [40] demonstrates that engineered phage particles are a proper strategy to enhance the efficacy and safety of viral particle-based vaccines. abstract: Vaccines are considered one of the most important bioproducts in medicine. Since the development of the smallpox vaccine in 1796, several types of vaccines for many diseases have been created. However, some vaccines have shown limitations as high cost and low immune responses. In that regard, bacteriophages have been proposed as an attractive alternative for the development of more cost-effective vaccines. Phage-displayed vaccines consists in the expression of antigens on the phage surface. This approach takes advantage of inherent properties of these particles such as their adjuvant capacity, economic production and high stability, among others. To date, three types of phage-based vaccines have been developed: phage-displayed, phage DNA and hybrid phage-DNA vaccines. Typically, phage display technology has been used for the identification of new and protective epitopes, mimotopes and antigens. In this context, phage particles represent a versatile, effective and promising alternative for the development of more effective vaccine delivery systems which should be highly exploited in the future. This review describes current advances in the development of bacteriophage-based vaccines, with special attention to vaccine delivery strategies. Moreover, the immunological aspects of phage-based vaccines, as well as the applications of phage display for vaccine development, are explored. Finally, important challenges and the future of phage-bases vaccines are discussed. url: https://doi.org/10.3390/vaccines8030504 doi: 10.3390/vaccines8030504 id: cord-325043-vqjhiv7p author: Gorbalenya, Alexander E. title: An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication date: 1989 words: 6805.0 sentences: 361.0 pages: flesch: 52.0 cache: ./cache/cord-325043-vqjhiv7p.txt txt: ./txt/cord-325043-vqjhiv7p.txt summary: title: An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication These observations, taken together with the results of comparative analysis of the positions occupied by respective proteins (domains) in viral multidomain proteins, suggest that all the NTP-motif-containing proteins of positive-strand RNA viruses are homologous, constituting a highly diverged monophyletic group. Preliminary comparative analysis of the amino acid sequences of the NTP-motif-eontaining proteins of positive-strand RNA viruses by use of the programs DIAGON and OPTAL (see Methods) revealed three distinct families and some additional proteins in whose close relatives the motif was not conserved. In the present study we demonstrate that in a highly diverged group including similar proteins of positive-strand RNA viruses, the consensus sequences of the NTP-motif constitute the most strictly conserved stretches, encompassing four of the five invariant amino acid residues. abstract: NTP-motif, a consensus sequence previously shown to be characteristic of numerous NTP-utilizing enzymes, was identified in nonstructural proteins of several groups of positive-strand RNA viruses. These groups include picorna-, alpha-, and coronaviruses infecting animals and como-, poty-, tobamo-, tricorna-, hordei-, and furoviruses of plants, totalling 21 viruses. It has been demonstrated that the viral NTP-motif-containing proteins constitute three distinct families, the sequences within each family being similar to each other at a statistically highly significant level. A lower, but still valid similarity has also been revealed between the families. An overall alignment has been generated, which includes several highly conserved sequence stretches. The two most prominent of the latter contain the socalled “A” and “B” sites of the NTP-motif, with four of the five invariant amino acid residues observed within these sequences. These observations, taken together with the results of comparative analysis of the positions occupied by respective proteins (domains) in viral multidomain proteins, suggest that all the NTP-motif-containing proteins of positive-strand RNA viruses are homologous, constituting a highly diverged monophyletic group. In this group the “A” and “B” sites of the NTP-motif are the most conserved sequences and, by inference, should play the principal role in the functioning of the proteins. A hypothesis is proposed that all these proteins posses NTP-binding capacity and possibly NTPase activity, performing some NTP-dependent function in viral RNA replication. The importance of phylogenetic analysis for the assessment of the significance of the occurrence of the NTP-motif (and of sequence motifs of this sort in general) in proteins is emphasized. url: https://www.ncbi.nlm.nih.gov/pubmed/2522556/ doi: 10.1007/bf02102483 id: cord-013348-lsksys56 author: Goto, Keiko title: Development of Monoclonal Antibodies and Antigen-Capture ELISA for Human Parechovirus Type 3 date: 2020-09-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Human parechovirus type 3 (HPeV3) is an etiologic agent of respiratory diseases, meningitis, and sepsis-like illness in both infants and adults. Monoclonal antibodies (mAbs) can be a promising diagnostic tool for antigenic diseases such as virus infection, as they offer a high specificity toward a specific viral antigen. However, to date, there is no specific mAb available for the diagnosis of HPeV3 infection. In this study, we developed and characterized mAbs specific for HPeV3 capsid protein VP0. We used cell-free, wheat germ-synthesized viral VP0 protein for immunizing BALB/c mice to generate hybridomas. From the resultant hybridoma clones, we selected nine clones producing mAbs reactive to the HPeV3-VP0 antigen, based on enzyme-linked immunosorbent assay (ELISA). Epitope mapping showed that these mAbs recognized three distinct domains in HPeV3 VP0. Six mAbs recognized HPeV3 specifically and the other three mAbs showed cross-reactivity with other HPeVs. Using the HPeV3-specific mAbs, we then developed an ELISA for viral antigen detection that could be reliably used for laboratory diagnosis of HPeV3. This ELISA system exhibited no cross-reactivity with other related viruses. Our newly developed mAbs would, thus, provide a useful set of tools for future research and ensure HPeV3-specific diagnosis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563955/ doi: 10.3390/microorganisms8091437 id: cord-020788-a33vcapl author: Gottardi, Cara J. title: Signals and Mechanisms of Sorting in Epithelial Polarity date: 2008-05-22 words: 13900.0 sentences: 598.0 pages: flesch: 39.0 cache: ./cache/cord-020788-a33vcapl.txt txt: ./txt/cord-020788-a33vcapl.txt summary: At the electron-microscopic level, one of the most apparent and fundamental features of this cell type is its polarized organization of intracellular organelles and its structurally and compositionally distinct lumenal (apical) and serosal (basolateral) plasma-membrane domains. As noted above, in hepatocytes all apical proteins studied to date make use of this indirect pathway for apical delivery (Bartles et al., 1987) , while cell lines derived from intestine and kidney can employ both routes for surface delivery (Matter et al., 1990; Casanovaet al., 1991; Low et al., 1991) While the details of the routes have been determined for a number of sorting pathways, the molecular signals and recognition components which control each of them are not well understood. The observation that the influenza and vesicular stomatitis viruses bud from opposite surface domains of polarized MDCK cells (Madin Darby Canine Kidney) (Rodriguez-Boulan and Sabatini, 1978) spawned an extensive search in which chimeric and deletion analyses were applied to the problem of identifying the underlying apical and basolateral sorting signals (reviewed in Caplan and Matlin, 1989) . abstract: This chapter discusses epithelial-membrane polarity, sorting pathways in polarized cells, and the sorting-signal paradigm. Polarized epithelial cells have long captured the attention of cell biologists and cell physiologists. At the electron-microscopic level, one of the most apparent and fundamental features of this cell type is its polarized organization of intracellular organelles and its structurally and compositionally distinct lumenal (apical) and serosal (basolateral) plasma-membrane domains. The polarized epithelial phenotype is an absolute necessity for organ-system function. In the most general sense, these cells organize to form a continuous, single layer of cells, or epithelium, which serves as a semi-permeable barrier between apposing and biologically distinct compartments. Within the tubules of the nephron, these cells orchestrate complex ion-transporting processes that ultimately control the overall fluid balance of the organism. At the surface of the gastrointestinal tract, specialized versions of this cell type control the digestion, absorption, and immuno-protection of the organism. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147917/ doi: 10.1016/s1569-2558(08)60020-x id: cord-287729-pl88otue author: Gray, Stewart M. title: Plant virus proteins involved in natural vector transmission date: 1996-07-31 words: 2228.0 sentences: 168.0 pages: flesch: 59.0 cache: ./cache/cord-287729-pl88otue.txt txt: ./txt/cord-287729-pl88otue.txt summary: Viral proteins mediate the binding of plant viruses to vector mouthparts and the transport of virus across vector-cell membranes. They further suggest that the am&-terminal region of the coat-protein monomers assembled into virus particles is not normally available for interaction with the aphids, but that HC mediates a conformational change in the amino termiof thecoat protein that allows binding of the virus ;o the aphid (Fig. 4C) .mission is regulated mainly by the codt protein''". Site-specific mutagenesis of cucumber mosaic virus (CuMV) has identified two regions of the coat protein thar are involved in efficient transmission, and has pinpointed the amino acids needed<''. These observations biggest that one or a few amino acid changes in the coat protein could alter the vectortransmission phenotype by pre\ enring direct interaction between the virus and the vector. the environment wtthln the food canal or binding of the virus tc) the vector, all resulting in the exposure >f cleavage sites on the coat proteins. abstract: Abstract Plant viruses transmitted by invertebrate vectors either reversibly bind to vector mouthparts or are internalized by the vector and later secreted. Viral proteins mediate the binding of plant viruses to vector mouthparts and the transport of virus across vector-cell membranes. Both mechanisms probably involve conformational changes of virus proteins during their association with the vector. url: https://www.ncbi.nlm.nih.gov/pubmed/8829333/ doi: 10.1016/0966-842x(96)10040-8 id: cord-325825-0lyt8gfq author: Griffiths, Samantha J. title: A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date: 2013-08-08 words: 12504.0 sentences: 601.0 pages: flesch: 45.0 cache: ./cache/cord-325825-0lyt8gfq.txt txt: ./txt/cord-325825-0lyt8gfq.txt summary: Host factors (HFs) which positively or negatively regulate HSV-1 replication were identified by screening a druggable genome siRNA library (4 siRNAs per gene) targeting 7,237 human genes against a HSV-1 reporter virus expressing the enhanced green fluorescent protein (eGFP; HSV-1 strain C12) in the epithelial Hela cell line, due to their ease of transfection and susceptibility to HSV-1 infection [34] . Combined bioinformatic analyses of protein interaction and siRNA depletion screens found a significant functional enrichment for proteins involved in transcription, and identified multi-protein complexes enriched for pro-viral HFs which strongly inhibited HSV-1 upon depletion, including the RNA-polymerase II, eIF3 and Mediator complexes ( Figure 3a) . Furthermore, qPCR analysis found depletion of Med23 inhibited the induction of IFN-l expression following HSV-1 infection of A549 cells in comparison to cells transfected with the RSCF siRNA control ( Figure 4e ). abstract: Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome. url: https://doi.org/10.1371/journal.ppat.1003514 doi: 10.1371/journal.ppat.1003514 id: cord-022262-ck2lhojz author: Gromeier, Matthias title: Genetics, Pathogenesis and Evolution of Picornaviruses date: 2007-09-02 words: 28035.0 sentences: 1423.0 pages: flesch: 46.0 cache: ./cache/cord-022262-ck2lhojz.txt txt: ./txt/cord-022262-ck2lhojz.txt summary: The following viruses have been recognized as picornaviruses on the basis of their genome sequences and physico-chemical properties as well as the result of comparative sequence analyses (see the section on Evolution): equine rhinovirus types I and 2, Aichi virus, porcine enterovirus, avian encephalomyelitis virus, infectious flacherie virus of silkworm Clusters of enteroviruses refer to groups of enteroviruses arranged predominantly according to genotypic kinship (Hyypia et al., 1997) . Briefly, when expression vectors ( Figure 12 .6E) consisting of a gag gene (encoding p17-p24; 1161 nt) of human immunodeficiency virus that was fused to the N-terminus of the poliovirus polyprotein (Andino et al., 1994; Mueller and Wimmer, 1998) were analysed after transfection into HeLa cells, the genomes were not only found to be severely impaired in viral replication but they were also genetically unstable (Mueller and Wimmer, 1997) . abstract: The discovery of viruses heralded an exciting new era for research in the medical and biological sciences. It has been realized that the cellular receptor guiding a virus to a target cell cannot be the sole determinant of a virus's pathogenic potential. Comparative analyses of the structures of genomes and their products have placed the picornaviruses into a large “picorna-like” virus family, in which they occupy a prominent place. Most human picornavirus infections are self-limiting, yet the enormously high rate of picornavirus infections in the human population can lead to a significant incidence of disease complications that may be permanently debilitating or even fatal. Picornaviruses employ one of the simplest imaginable genetic systems: they consist of single-stranded RNA that encodes only a single multidomain polypeptide, the polyprotein. The RNA is packaged into a small, rigid, naked, and icosahedral virion whose proteins are unmodified except for a myristate at the N-termini of VP4. The RNA itself does not contain modified bases. The key to ultimately understanding picornaviruses may be to rationalize the huge amount of information about these viruses from the perspective of evolution. It is possible that the replicative apparatus of picornaviruses originated in the precellular world and was subsequently refined in the course of thousands of generations in a slowly evolving environment. Picornaviruses cultivated the art of adaptation, which has allowed them to “jump” into new niches offered in the biological world. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155501/ doi: 10.1016/b978-012220360-2/50013-1 id: cord-268416-8hw80qx8 author: Grunewald, Matthew E. title: The coronavirus nucleocapsid protein is ADP-ribosylated date: 2018-04-01 words: 4795.0 sentences: 263.0 pages: flesch: 50.0 cache: ./cache/cord-268416-8hw80qx8.txt txt: ./txt/cord-268416-8hw80qx8.txt summary: While screening for ADP-ribosylated proteins during coronavirus (CoV) infection, we detected a ~55 kDa ADP-ribosylated protein in mouse hepatitis virus (MHV)-infected cells and in virions, which we identified as the viral nucleocapsid (N) protein. To identify potential targets of the CoV macrodomain, we analyzed infected cells for changes in ADP-ribosylation patterns utilizing antibodies specific for ADPr. We focused on cells infected with a murine CoV, mouse hepatitis virus (MHV). If the macrodomain was indeed removing the ADPr from the N protein, we would expect to see increased N protein ADP-ribosylation in cells infected with mutant virus compared to wild-type infected cells. To determine if N protein expressed in the absence of CoV infection could be ADP-ribosylated in cell culture, we transduced Vero cells with VEEV replicon particles (VRPs) encoding the MERS-CoV N protein or control GFP at different MOIs . abstract: ADP-ribosylation is a common post-translational modification, although how it modulates RNA virus infection is not well understood. While screening for ADP-ribosylated proteins during coronavirus (CoV) infection, we detected a ~55 kDa ADP-ribosylated protein in mouse hepatitis virus (MHV)-infected cells and in virions, which we identified as the viral nucleocapsid (N) protein. The N proteins of porcine epidemic diarrhea virus (PEDV), severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV were also ADP-ribosylated. ADP-ribosylation of N protein was also observed in cells exogenously expressing N protein by transduction using Venezuelan equine encephalitis virus replicon particles (VRPs). However, plasmid-derived N protein was not ADP-ribosylated following transient transfection but was ADP-ribosylated after MHV infection, indicating that this modification requires virus infection. In conclusion, we have identified a novel post-translation modification of the CoV N protein that may play a regulatory role for this important structural protein. url: https://doi.org/10.1016/j.virol.2017.11.020 doi: 10.1016/j.virol.2017.11.020 id: cord-034823-ogwjzfgf author: Guo, Hao-Bo title: A Suggestion of Converting Protein Intrinsic Disorder to Structural Entropy Using Shannon’s Information Theory date: 2019-06-14 words: 7021.0 sentences: 377.0 pages: flesch: 55.0 cache: ./cache/cord-034823-ogwjzfgf.txt txt: ./txt/cord-034823-ogwjzfgf.txt summary: We propose a framework to convert the protein intrinsic disorder content to structural entropy (H) using Shannon''s information theory (IT). Hence, it is useful to know the relationships between the intrinsic structural entropies and the information that can be derived (Equation (3)) from the residual disorder contents, which, in turn, can be predicted based on the protein amino acid sequences. In the CR-space, Ci sets the upper limit and Ri gives the intrinsic ratio between the two quantities of the total Hi and Ii of the i-th protein Pi. Based on the Gaussian distribution in both log2C and log2R, the protein distributions in the CR-space are represented in Figure 2 , for proteins expressed in representative prokaryotes (bacteria and archaea, Figure 2A ), eukaryotes ( Figure 2B ), viruses ( Figure 2C ), and datasets collected from the DisProt database [25] and protein data bank (PDB) [26] ( Figure 2D ). abstract: We propose a framework to convert the protein intrinsic disorder content to structural entropy (H) using Shannon’s information theory (IT). The structural capacity (C), which is the sum of H and structural information (I), is equal to the amino acid sequence length of the protein. The structural entropy of the residues expands a continuous spectrum, ranging from 0 (fully ordered) to 1 (fully disordered), consistent with Shannon’s IT, which scores the fully-determined state 0 and the fully-uncertain state 1. The intrinsically disordered proteins (IDPs) in a living cell may participate in maintaining the high-energy-low-entropy state. In addition, under this framework, the biological functions performed by proteins and associated with the order or disorder of their 3D structures could be explained in terms of information-gains or entropy-losses, or the reverse processes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515080/ doi: 10.3390/e21060591 id: cord-337032-s4g4g80w author: Gupta, Manoj Kumar title: In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel date: 2020-04-15 words: 3964.0 sentences: 191.0 pages: flesch: 52.0 cache: ./cache/cord-337032-s4g4g80w.txt txt: ./txt/cord-337032-s4g4g80w.txt summary: Considering this, in the present study, authors employed computational approaches for studying the structure as well as function of the human ''SARS-CoV2 E'' protein as well as its interaction with various phytochemicals. Result obtained revealed that α-helix and loops present in this protein experience random movement under optimal condition, which in turn modulate ion channel activity; thereby aiding the pathogenesis caused via SARS-CoV2 in human and other vertebrates. By considering the above information, in the present study, authors employed computational approach for identifying the best possible structure of the ''SARS-CoV2 E'' protein present in the PDB database to understand its structure and function as well as its behaviour towards various phytochemicals. Subsequently, molecular docking of the ''SARS-CoV2 E'' protein with ligands having 250 conformations using the AutoDock tool revealed that the best ten phytochemicals with minimal binding energy are TIP006452 (Belachinal), TIP005365 (Macaflavanone E), TIP003272 (Vibsanol B), TIP003258 (14 R Ã ,15-Epoxyvibsanin C), TIP005363 (Macaflavanone C), TIP000749 (Luzonoid D), TIP008605 (Grossamide K), TIP009461 ((-)-Blestriarene C), TIP005366 (Macaflavanone F) and TIP005783 (Dolichosterone). abstract: Recent outbreak of Coronavirus disease (COVID-19) pandemic around the world is associated with ‘severe acute respiratory syndrome’ (SARS-CoV2) in humans. SARS-CoV2 is an enveloped virus and E proteins present in them are reported to form ion channels, which is mainly associated with pathogenesis. Thus, there is always a quest to inhibit these ion channels, which in turn may help in controlling diseases caused by SARS-CoV2 in humans. Considering this, in the present study, authors employed computational approaches for studying the structure as well as function of the human ‘SARS-CoV2 E’ protein as well as its interaction with various phytochemicals. Result obtained revealed that α-helix and loops present in this protein experience random movement under optimal condition, which in turn modulate ion channel activity; thereby aiding the pathogenesis caused via SARS-CoV2 in human and other vertebrates. However, after binding with Belachinal, Macaflavanone E, and Vibsanol B, the random motion of the human ‘SARS-CoV2 E’ protein gets reduced, this, in turn, inhibits the function of the ‘SARS-CoV2 E’ protein. It is pertinent to note that two amino acids, namely VAL25 and PHE26, play a key role while interacting with these three phytochemicals. As these three phytochemicals, namely, Belachinal, Macaflavanone E & Vibsanol B, have passed the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) property as well as ‘Lipinski’s Rule of 5s’, they may be utilized as drugs in controlling disease caused via SARS-COV2, after further investigation. Communicated by Ramaswamy H. Sarma url: https://doi.org/10.1080/07391102.2020.1751300 doi: 10.1080/07391102.2020.1751300 id: cord-016419-v1f6dx3e author: Gupta, Varsha title: Production of Recombinant Pharmaceutical Proteins date: 2016-10-23 words: 9648.0 sentences: 602.0 pages: flesch: 50.0 cache: ./cache/cord-016419-v1f6dx3e.txt txt: ./txt/cord-016419-v1f6dx3e.txt summary: Usage of recombinant DNA technology for large-scale production of proteins requires ample amount of time, labor, and resources, but it also offers many opportunities for economic growth. The recombinant proteins approved by FDA are obtained either from Escherichia coli or other prokaryotes; from Saccharomyces cerevisiae or other fungal species; from insect cells , mammalian cells , or human cells ; or from transgenic plants or animals. Their advantages are low cost, high mass production, scale-up, lack of human pathogens , and addition of eukaryotic PTMs. The fi rst recombinant protein obtained in 1986 from tobacco plants was human growth hormone . The vector can be modifi ed to express genes for insulin (tomato) or Hep-B surface antigen (HBsAg) for recombinant therapeutics providing a human glycosylation pattern have increased attention, and the efforts are being made for the development of novel glycoengineered cell lines for production of fully glycosylated protein therapeutic. abstract: The proteins produced in the body control and mediate the metabolic processes and help in its routine functioning. Any kind of impairment in protein production, such as production of mutated protein, or misfolded protein, leads to disruption of the pathway controlled by that protein. This may manifest in the form of the disease. However, these diseases can be treated, by supplying the protein from outside or exogenously. The supply of active exogenous protein requires its production on large scale to fulfill the growing demand. The process is complex, requiring higher protein expression, purification, and processing. Each product needs unique settings or standardizations for large-scale production and purification. As only large-scale production can fulfill the growing demand, thus it needs to be cost-effective. The tools of genetic engineering are utilized to produce the proteins of human origin in bacteria, fungi, insect, or mammalian host. Usage of recombinant DNA technology for large-scale production of proteins requires ample amount of time, labor, and resources, but it also offers many opportunities for economic growth. After reading this chapter, readers would be able to understand the basics about production of recombinant proteins in various hosts along with the advantages and limitations of each host system and properties and production of some of the important pharmaceutical compounds and growth factors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120688/ doi: 10.1007/978-981-10-0875-7_4 id: cord-348972-r94fhpe0 author: Gussow, Ayal B. title: Machine-learning approach expands the repertoire of anti-CRISPR protein families date: 2020-07-29 words: 9653.0 sentences: 505.0 pages: flesch: 54.0 cache: ./cache/cord-348972-r94fhpe0.txt txt: ./txt/cord-348972-r94fhpe0.txt summary: The most striking and obvious common feature of the Acrs is their small size (weighted mean Acr length: 104 aa, Table 1 ), and the tendency to form sets of small proteins that are encoded by co-directional and closely spaced genes in (pro)virus genomes (hereafter directons; Fig. 1 , Table 1 ). As genes encoding Acrs tend to form small directons, we sought to estimate a heuristic maximum threshold for the mean directon size in a candidate family that would enrich our protein set for true Acrs. The initial set consisted of 232,616 clusters and was first filtered for clusters that included at least one member with an HTH-domain-containing protein encoded downstream, and at least one member from a self-targeting genome, two hallmark Acr characteristics 20 . abstract: The CRISPR-Cas are adaptive bacterial and archaeal immunity systems that have been harnessed for the development of powerful genome editing and engineering tools. In the incessant host-parasite arms race, viruses evolved multiple anti-defense mechanisms including diverse anti-CRISPR proteins (Acrs) that specifically inhibit CRISPR-Cas and therefore have enormous potential for application as modulators of genome editing tools. Most Acrs are small and highly variable proteins which makes their bioinformatic prediction a formidable task. We present a machine-learning approach for comprehensive Acr prediction. The model shows high predictive power when tested against an unseen test set and was employed to predict 2,500 candidate Acr families. Experimental validation of top candidates revealed two unknown Acrs (AcrIC9, IC10) and three other top candidates were coincidentally identified and found to possess anti-CRISPR activity. These results substantially expand the repertoire of predicted Acrs and provide a resource for experimental Acr discovery. url: https://www.ncbi.nlm.nih.gov/pubmed/32728052/ doi: 10.1038/s41467-020-17652-0 id: cord-319658-u0wjgw50 author: Guven-Maiorov, Emine title: Structural host-microbiota interaction networks date: 2017-10-12 words: 4666.0 sentences: 294.0 pages: flesch: 40.0 cache: ./cache/cord-319658-u0wjgw50.txt txt: ./txt/cord-319658-u0wjgw50.txt summary: To date, challenges in experimental techniques limit large-scale characterization of HMIs. Here we highlight an area in its infancy which we believe will increasingly engage the computational community: predicting interactions across kingdoms, and mapping these on the host cellular networks to figure out how commensal and pathogenic microbiota modulate the host signaling and broadly cross-species consequences. Systems biology approaches that integrate the HMIs with host endogenous protein interaction networks reveal the systematic trends in virulence strategies of pathogens. The availability of genome-wide high throughput omics data makes it possible to associate microbiota with certain host phenotypes at multiple levels and construct host-pathogen interaction networks at the transcriptome [21], proteome Combinatorial effects of microbial effectors and the active host pathways determine the cell response. Mimicry of interactions of critical regulatory nodes in core network modules in the immune system, may be a major way through which pathogens adversely subvert-and commensal microbiota may beneficially modulate-the host cell. abstract: Hundreds of different species colonize multicellular organisms making them “metaorganisms”. A growing body of data supports the role of microbiota in health and in disease. Grasping the principles of host-microbiota interactions (HMIs) at the molecular level is important since it may provide insights into the mechanisms of infections. The crosstalk between the host and the microbiota may help resolve puzzling questions such as how a microorganism can contribute to both health and disease. Integrated superorganism networks that consider host and microbiota as a whole–may uncover their code, clarifying perhaps the most fundamental question: how they modulate immune surveillance. Within this framework, structural HMI networks can uniquely identify potential microbial effectors that target distinct host nodes or interfere with endogenous host interactions, as well as how mutations on either host or microbial proteins affect the interaction. Furthermore, structural HMIs can help identify master host cell regulator nodes and modules whose tweaking by the microbes promote aberrant activity. Collectively, these data can delineate pathogenic mechanisms and thereby help maximize beneficial therapeutics. To date, challenges in experimental techniques limit large-scale characterization of HMIs. Here we highlight an area in its infancy which we believe will increasingly engage the computational community: predicting interactions across kingdoms, and mapping these on the host cellular networks to figure out how commensal and pathogenic microbiota modulate the host signaling and broadly cross-species consequences. url: https://doi.org/10.1371/journal.pcbi.1005579 doi: 10.1371/journal.pcbi.1005579 id: cord-293798-qc22cps9 author: Gómez-Mascaraque, Laura G. title: Nanostructuring Biopolymers for Improved Food Quality and Safety date: 2018-04-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Food-grade biopolymers, apart from their inherent nutritional properties, can be tailored designed for improving food quality and safety, either serving as delivery vehicles for bioactive molecules, or as novel packaging components, not only improving the transport properties of biobased packaging structures, but also imparting active antibacterial and antiviral properties. In this chapter, the potential of different food-grade biopolymers (mainly proteins and carbohydrates but also some biopolyesters) to serve as encapsulating matrices for the protection of sensitive bioactives or as nanostructured packaging layers to improve transport properties and control the growth of pathogenic bacteria and viruses are described based on some developments carried out by the authors, as well as the most prominent works found in literature in this area. url: https://api.elsevier.com/content/article/pii/B9780128114490000025 doi: 10.1016/b978-0-12-811449-0.00002-5 id: cord-022354-aqtceqqo author: HUNTER, ERIC title: Membrane Insertion and Transport of Viral Glycoproteins: A Mutational Analysis date: 2012-12-02 words: 17747.0 sentences: 697.0 pages: flesch: 44.0 cache: ./cache/cord-022354-aqtceqqo.txt txt: ./txt/cord-022354-aqtceqqo.txt summary: second apolar region in gp 37 consists of a 27 amino acid long stretch of hydrophobic residues near the carboxy terminus that functions during translation to stop the movement of the protein into the lumen of the rough endoplasmic reticulum (RER) and to anchor the complex in the membrane. In order to examine the role of the signal peptide in RSV glycoprotein biosynthesis we constructed a series of deletion mutations within the 5'' coding region of the env gene using the double-stranded exonuclease BaBl. Oligonucleotide linkers of the sequence CATCGATG were ligated to the ends of the truncated molecules to introduce a unique restriction endonuclease cleavage site and to replace the deleted in-frame AUG. We found that replacement of the nonconserved region of the cytoplasmic domain with a longer unrelated sequence of amino acids from SV40 vector sequences (mutant Cl) did not alter the rate of transport to the Golgi apparatus nor the appearance of the glycoprotein on the cell surface. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155604/ doi: 10.1016/b978-0-12-203460-2.50007-x id: cord-022200-hqc8r31t author: HYATT, ALEX D. title: Protein A–Gold: Nonspecific Binding and Cross-Contamination date: 2012-12-02 words: 3586.0 sentences: 225.0 pages: flesch: 56.0 cache: ./cache/cord-022200-hqc8r31t.txt txt: ./txt/cord-022200-hqc8r31t.txt summary: Some potential problems associated with protein Α -g o l d labeling are also associated with other immunocytochemical techniques, namely nonspecific staining (for example, nonspecific antibodies and electrostatic at tachment; Taylor, 1978; Behnke et al., 1986; Gosselin et al., 1986; Birrell et al., 1987) . In double-labeling experiments cross-contamination is now recognized as a problem which arises from the affinity which protein A possesses for different regions of IgG antibodies, namely the Fc and Fab regions (Roth, 1982; Endresen, 1979; Zikan, 1980) . If the larger of the gold probes is used for the visualization of the first antigen, many potential Fc binding sites (unoccupied protein A) are available for the second immunoglobulin and significant cross-contamination may therefore result. If protein Α-gold is the label, and nonspecific binding and cross-contamination are persistent problems in spite of the addition of excess free protein A, high-affinity stabilizers, adsorption of contaminat ing antibodies, and colloidal gold, then alternative labeling techniques should be pursued and evaluated. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155432/ doi: 10.1016/b978-0-12-333928-7.50007-1 id: cord-279691-v5kpmk0b author: Hagemeijer, Marne C. title: Biogenesis and Dynamics of the Coronavirus Replicative Structures date: 2012-11-21 words: 9036.0 sentences: 483.0 pages: flesch: 43.0 cache: ./cache/cord-279691-v5kpmk0b.txt txt: ./txt/cord-279691-v5kpmk0b.txt summary: Upon infection, coronaviruses extensively rearrange cellular membranes into organelle-like replicative structures that consist of double-membrane vesicles and convoluted membranes to which the nonstructural proteins involved in RNA synthesis localize. This review will summarize the current knowledge on the biogenesis of the replicative structures, the membrane anchoring of the replication-transcription complexes, and the location of viral RNA synthesis, with particular focus on the dynamics of the coronavirus replicative structures and individual replication-associated proteins. A distinctive common feature of +RNA viruses is the replication of their genomes in the cytoplasm of the host cell in association with rearranged cellular membranes that are remodeled into organelle-like membranous structures to which the viral replication-transcription complexes (RTCs) localize. The first detectable membrane rearrangements in CoV-infected cells are 200 to 350 nm organelle-like structures that have been described for both MHV [47, 62] and the SARS-CoV [5, 63] and consist of spherical vesicles containing double lipid bilayers, termed DMVs ( Figure 2 ). abstract: Coronaviruses are positive-strand RNA viruses that are important infectious agents of both animals and humans. A common feature among positive-strand RNA viruses is their assembly of replication-transcription complexes in association with cytoplasmic membranes. Upon infection, coronaviruses extensively rearrange cellular membranes into organelle-like replicative structures that consist of double-membrane vesicles and convoluted membranes to which the nonstructural proteins involved in RNA synthesis localize. Double-stranded RNA, presumably functioning as replicative intermediate during viral RNA synthesis, has been detected at the double-membrane vesicle interior. Recent studies have provided new insights into the assembly and functioning of the coronavirus replicative structures. This review will summarize the current knowledge on the biogenesis of the replicative structures, the membrane anchoring of the replication-transcription complexes, and the location of viral RNA synthesis, with particular focus on the dynamics of the coronavirus replicative structures and individual replication-associated proteins. url: https://www.ncbi.nlm.nih.gov/pubmed/23202524/ doi: 10.3390/v4113245 id: cord-343791-0vykwml5 author: Hainline, Kelly M. title: Progress towards the clinical translation of bio-inspired peptide and protein assemblies date: 2017-11-08 words: 7314.0 sentences: 416.0 pages: flesch: 42.0 cache: ./cache/cord-343791-0vykwml5.txt txt: ./txt/cord-343791-0vykwml5.txt summary: These include spherical assemblies such as virus-like particles, designed protein nanoparticles, and peptide amphiphiles (Figure 1) ; and elongated structures such as β-sheet nanofibers, fiber-forming peptide amphiphiles, and filamentous phage (Figure 2) . [17, 18] Owing to their lack of a viral genome, VLP-based vaccines circumvent some risks associated Supramolecular materials composed of proteins and peptides have been receiving considerable attention toward a range of diseases and conditions from vaccines to drug delivery. [19] As alternatives to these previous platforms, VLPs were developed to display an array of epitopes that mimic the surface of native viruses more effectively than subunit or peptide vaccines, thus improving their immunogenic properties. Whereas synthetic peptides are usually not sufficiently immunogenic and require adjuvants, the Burkhard group has developed a self-assembling protein nanoparticle platform that displays both B and T cell epitopes to produce a vaccine with self-adjuvanting qualities. abstract: Supramolecular materials composed of proteins and peptides have been receiving considerable attention towards a range of diseases and conditions from vaccines to drug delivery. Owing to the relative newness of this class of materials, the bulk of work to date has been preclinical. However, examples of approved treatments particularly in vaccines, dentistry, and hemostasis are demonstrating the translational potential of supramolecular polypeptides. Here we describe critical milestones in the clinical development of this class of materials and describe currently approved supramolecular polypeptide therapies. Additional examples of not-yet-approved materials that are steadily advancing towards clinical use are also featured. Spherical assemblies such as virus-like particles (VLPs), designed protein nanoparticles, and spherical peptide amphiphiles are highlighted, followed by fiber-forming systems such as fibrillizing peptides, fiber-forming peptide-amphiphiles, and filamentous bacteriophages. url: https://www.ncbi.nlm.nih.gov/pubmed/29115746/ doi: 10.1002/adhm.201700930 id: cord-275993-isff6lp2 author: Han, Dong P title: Development of a safe neutralization assay for SARS-CoV and characterization of S-glycoprotein date: 2004-08-15 words: 5598.0 sentences: 308.0 pages: flesch: 52.0 cache: ./cache/cord-275993-isff6lp2.txt txt: ./txt/cord-275993-isff6lp2.txt summary: Similar to other coronaviruses, spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. S-protein of coronaviruses, which is thought to function as a trimer (Delmas and Laude, 1990) , is responsible for both binding to cellular receptors and inducing membrane fusion for virus entry into target cells (Collins et al., 1982; Godet et al., 1994; Kubo et al., 1994) . Despite difficulties in detecting S-protein directly by immunoassays, proteins expressed from both pcDNA-S and pHCMV-S constructs were able to pseudotype MuLV particles to produce SARS pseudoviruses that could readily infect Vero E6 cells (Fig. 3A) . To assess whether SARS pseudoviruses we generated could be used to quantify virus-neutralizing antibodies, we examined their susceptibility to convalescent sera from SARS-CoV-infected patients. Pseudotyping of murine leukemia virus with the envelope glycoproteins of HIV generates a retroviral vector with specificity of infection for CD4-expressing cells abstract: The etiological agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus SARS-CoV. Similar to other coronaviruses, spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. Accordingly, S-protein plays an important role in virus infection cycle and is the primary target of neutralizing antibodies. To begin to understand its biochemical and immunological properties, we expressed both full-length and ectodomain of the protein in various primate cells. Our results show that the protein has an electrophoretic mobility of about 160–170 kDa. The protein is glycosylated with high mannose and/or hybrid oligosaccharides, which account for approximately 30 kDa of the apparent protein mass. The detection of S-protein by immunoassays was difficult using human convalescent sera, suggesting that the protein may not elicit strong humoral immune response in virus-infected patients. We were able to pseudotype murine leukemia virus particles with S-protein and produce SARS pseudoviruses. Pseudoviruses infected Vero E6 cells in a pH-independent manner and the infection could be specifically inhibited by convalescent sera. Consistent with low levels of antibodies against S-protein, neutralizing activity was weak with 50% neutralization titers ranging between 1:15 to 1:25. To facilitate quantifying pseudovirus-infected cells, which are stained blue with X-Gal, we devised an automated procedure using an ELISPOT analyzer. The high-throughput capacity of this procedure and the safety of using SARS pseudoviruses should make possible large-scale analyses of neutralizing antibody responses against SARS-CoV. url: https://www.ncbi.nlm.nih.gov/pubmed/15262502/ doi: 10.1016/j.virol.2004.05.017 id: cord-272260-88l9bq4i author: Han, L.Y. title: Prediction of functional class of novel viral proteins by a statistical learning method irrespective of sequence similarity date: 2005-01-05 words: 4116.0 sentences: 220.0 pages: flesch: 47.0 cache: ./cache/cord-272260-88l9bq4i.txt txt: ./txt/cord-272260-88l9bq4i.txt summary: The web-based software SVMProt (http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi) to some extent assigns protein functional family irrespective of sequence similarity and has been found to be useful for studying distantly related proteins [Cai, C.Z., Han, L.Y., Ji, Z.L., Chen, X., Chen, Y.Z., 2003. This suggests that SVMProt to some extent is capable of functional class assignment irrespective of sequence similarity and it is potentially useful for facilitating functional study of novel viral proteins. These include evolutionary analysis (Benner et al., 2000; Eisen, 1998) , hidden Markov models (Fujiwara and Asogawa, 2002) , structural consideration (Di Gennaro et al., 2001; Teichmann et al., 2001) , protein/gene fusion (Enright et al., 1999; Marcotte et al., 1999) , proteinprotein interactions (Bock and Gough, 2001) , motifs (Hodges and Tsai, 2002) , family classification by sequence clustering (Enright et al., 2002) , and functional family prediction by statistical learning methods (Cai et al., 2003 Han et al., 2004; Jensen et al., 2002; Karchin et al., 2002) . abstract: The function of a substantial percentage of the putative protein-coding open reading frames (ORFs) in viral genomes is unknown. As their sequence is not similar to that of proteins of known function, the function of these ORFs cannot be assigned on the basis of sequence similarity. Methods complement or in combination with sequence similarity-based approaches are being explored. The web-based software SVMProt (http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi) to some extent assigns protein functional family irrespective of sequence similarity and has been found to be useful for studying distantly related proteins [Cai, C.Z., Han, L.Y., Ji, Z.L., Chen, X., Chen, Y.Z., 2003. SVM-Prot: web-based support vector machine software for functional classification of a protein from its primary sequence. Nucleic Acids Res. 31(13): 3692–3697]. Here 25 novel viral proteins are selected to test the capability of SVMProt for functional family assignment of viral proteins whose function cannot be confidently predicted on by sequence similarity methods at present. These proteins are without a sequence homolog in the Swissprot database, with its precise function provided in the literature, and not included in the training sets of SVMProt. The predicted functional classes of 72% of these proteins match the literature-described function, which is compared to the overall accuracy of 87% for SVMProt functional class assignment of 34 582 proteins. This suggests that SVMProt to some extent is capable of functional class assignment irrespective of sequence similarity and it is potentially useful for facilitating functional study of novel viral proteins. url: https://api.elsevier.com/content/article/pii/S0042682204006907 doi: 10.1016/j.virol.2004.10.020 id: cord-323072-4rsgeag7 author: Han, Xueqing title: The expression of SARS–CoV M gene in P. Pastoris and the diagnostic utility of the expression product date: 2004-12-01 words: 3741.0 sentences: 185.0 pages: flesch: 54.0 cache: ./cache/cord-323072-4rsgeag7.txt txt: ./txt/cord-323072-4rsgeag7.txt summary: Since the outbreak of SARS in 2003, several laboratory diagnostic methods have been established, including real-time RT-PCR assay, whole-virus-based immunofluorescence assay (IFA), recombinant protein-based enzyme-linked immunosorbent assay (ELISA) and immunochromatographic tests, antigencapturing enzyme-linked immunosorbent assay, and Western blot (WB) assay. To test whether the recombinant M protein is effective as an ELISA antigen for detecting SARS-CoV patient serum, the sera from four healthy people and four SARS patients were used. Detection results of eight human sera by ELISA using purified recombinant M protein as antigen.# 1-4: sera from four healthy people, respectively, # 5-8: sera from four SARS patients, respectively. The results were in complete accordance with those of other assays, thus indicating that the recombinant M protein may be useful as an ELISA antigen for detecting specific antibodies to SARS-CoV in human sera. Recombinant protein-based enzyme-linked imunosorbent assay and immunochromatographic tests for detection of immunoglobulin G antibodies to severe acute respiratory syndrome (SARS) coronavirus in SARS patients abstract: High-level protein expression is an important means of obtaining large amounts of viral proteins to investigate further their biological properties. To express the membrane (M) protein of SARS–CoV at high-level in vitro, the M gene fragment was amplified and cloned it into the Pichia Pastoris expression vector pPICZαA. SDS–PAGE and Western blotting analysis of the induced products of recombinant yeast transformant indicated that successful high-level expression of M protein was achieved, and that the expression product was similar antigenically to the natural protein. Purified recombinant M protein was used subsequently as an ELISA antigen for detection of eight serum samples screened previously by whole virus ELISA and immunofluorescence assay, and consistent results were obtained. These findings suggest that the recombinant M protein may be useful as a diagnostic reagent. url: https://api.elsevier.com/content/article/pii/S0166093404002472 doi: 10.1016/j.jviromet.2004.08.015 id: cord-307811-6e3j0pn7 author: Hao, Wei title: Binding of the SARS-CoV-2 Spike Protein to Glycans date: 2020-07-02 words: 5665.0 sentences: 299.0 pages: flesch: 54.0 cache: ./cache/cord-307811-6e3j0pn7.txt txt: ./txt/cord-307811-6e3j0pn7.txt summary: Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. Previous studies of many other viruses suggested that SARS-CoV-2 S protein may use other molecules on host cell surface as attachment factors to facilitate binding to the high-affinity receptor ACE2. 36 A recent study suggested that HS may bind to the receptor binding domain (RBD, the C-terminal region of the S1 subunit, Fig. 2 ) of the SARS-CoV-2 spike protein and change its conformation. 38 In this study, we systematically examined and compared the binding of the SARS-CoV-2 S protein subunits, full-length molecule and its trimer to different HS using microarray experiments (Fig. 2) . In addition to binding protein-based receptors, many viruses can interact with cell surface glycans, including GAGs and sialic acid-containing oligosaccharides. abstract: The pandemic of SARS-CoV-2 has caused a high number of deaths in the world. To combat it, it is necessary to develop a better understanding of how the virus infects host cells. Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. In this study, we examined and compared the binding of the subunits and spike (S) proteins of SARS-CoV-2 and SARS-CoV, MERS-CoV to these glycans. Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner, the length of HS is not a critical factor for the binding, and no binding with sialic acid residues was detected. Overall, this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells, and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses. url: https://doi.org/10.1101/2020.05.17.100537 doi: 10.1101/2020.05.17.100537 id: cord-147565-mtdhdkc1 author: Harmalkar, Ameya title: Advances to tackle backbone flexibility in protein docking date: 2020-10-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Computational docking methods can provide structural models of protein-protein complexes, but protein backbone flexibility upon association often thwarts accurate predictions. In recent blind challenges, medium or high accuracy models were submitted in less than 20% of the"difficult"targets (with significant backbone change or uncertainty). Here, we describe recent developments in protein-protein docking and highlight advances that tackle backbone flexibility. In molecular dynamics and Monte Carlo approaches, enhanced sampling techniques have reduced time-scale limitations. Internal coordinate formulations can now capture realistic motions of monomers and complexes using harmonic dynamics. And machine learning approaches adaptively guide docking trajectories or generate novel binding site predictions from deep neural networks trained on protein interfaces. These tools poise the field to break through the longstanding challenge of correctly predicting complex structures with significant conformational change. url: https://arxiv.org/pdf/2010.07455v1.pdf doi: nan id: cord-329840-f3dsu36p author: Hati, Sanchita title: Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor date: 2020-05-11 words: 2497.0 sentences: 173.0 pages: flesch: 51.0 cache: ./cache/cord-329840-f3dsu36p.txt txt: ./txt/cord-329840-f3dsu36p.txt summary: In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. In the backdrop of significant mortality rate for SARS-CoV-2 (hereinafter referred to as CoV-2) infection, it is important to know if the thiol-disulfide balance plays any role on the binding of the spike glycoprotein on to the host cell receptor protein ACE2. Using these reported structures, molecular dynamics simulations and electrostatic field calculations were performed to explore the impact of thioldisulfide balance on CoV/CoV-2 and ACE2 binding affinities. The structural and dynamical changes due to the change in the redox states of cysteines in the interacting proteins were analyzed and their effects on binding free energies were studied. abstract: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding provides a molecular basis for the severity of COVID-19 infection due to the oxidative stress. url: https://doi.org/10.1101/2020.05.07.083147 doi: 10.1101/2020.05.07.083147 id: cord-270594-62xotol3 author: He, Lei title: Identification and characterization of vp7 gene in Bombyx mori cytoplasmic polyhedrosis virus date: 2017-09-05 words: 4444.0 sentences: 266.0 pages: flesch: 55.0 cache: ./cache/cord-270594-62xotol3.txt txt: ./txt/cord-270594-62xotol3.txt summary: In this study, the viral structural protein 7 (VP7) polyclonal antibody was prepared with immunized mouse to explore the presence of small VP7 gene-encoded proteins in Bombyx mori cytoplasmic polyhedrosis virus. The replication of BmCPV genome in the cultured cells and midgut of silkworm was decreased by reducing the expression level of vp7 gene using RNA interference. In immunoprecipitation experiments, using a polyclonal antiserum directed against the VP7, one additional shorter band in BmCPV infected midguts was detected, and then the band was analyzed with mass spectrum (MS), the MS results showed thatone candidate interacted protein (VP7 voltage-dependent anion-selective channel-like isoform, VDAC) was identified from silkworm. A novel protein was detected from the overexpression of vp7 gene in the BmCPV infected cultured cells, with VP7 antibody. Total proteins from the BmCPV infected silkworm midguts (from the first day to the twelfth day) were also extracted, and detected with VP7 antibody. abstract: The genome of Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) contains 10 double stranded RNA segments (S1–S10). The segment 7 (S7) encodes 50 kDa protein which is considered as a structural protein. The expression pattern and function of p50 in the virus life cycle are still unclear. In this study, the viral structural protein 7 (VP7) polyclonal antibody was prepared with immunized mouse to explore the presence of small VP7 gene-encoded proteins in Bombyx mori cytoplasmic polyhedrosis virus. The expression pattern of vp7 gene was investigated by its overexpression in BmN cells. In addition to VP7, supplementary band was identified with western blotting technique. The virion, BmCPV infected cells and midguts were also examined using western blotting technique. 4, 2 and 5 bands were detected in the corresponding samples, respectively. The replication of BmCPV genome in the cultured cells and midgut of silkworm was decreased by reducing the expression level of vp7 gene using RNA interference. In immunoprecipitation experiments, using a polyclonal antiserum directed against the VP7, one additional shorter band in BmCPV infected midguts was detected, and then the band was analyzed with mass spectrum (MS), the MS results showed thatone candidate interacted protein (VP7 voltage-dependent anion-selective channel-like isoform, VDAC) was identified from silkworm. We concluded that the novel viral product was generated with a leaky scanning mechanism and the VDAC may be an interacted protein with VP7. url: https://api.elsevier.com/content/article/pii/S0378111917304985 doi: 10.1016/j.gene.2017.06.048 id: cord-002100-dt5zvebj author: He, Yonghua title: Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF) date: 2016-06-17 words: 6795.0 sentences: 336.0 pages: flesch: 45.0 cache: ./cache/cord-002100-dt5zvebj.txt txt: ./txt/cord-002100-dt5zvebj.txt summary: Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. Epidermal growth factor protein from humans was produced in soybean seeds by constructing a plant gene expression cassette that involved a synthetic codon optimized EGF nucleotide sequence (protein sequence from Genbank accession CCQ43157). To assess the bioactivity of soybean-produced hEGF, samples were prepared from both ShEGF transgenic soybean lines and nontransgenic controls that were used to stimulate HeLa cells to induce EGFR internalization, degradation and phosphorylation. In contrast, samples prepared from control nontransgenic soybeans exhibited no apparent bioactivity showing the degradation and phosphorylation of EGFR is the result of EGF binding of either commercial rhEGF added to the media or from the hEGF produced by the transgenic soybeans. abstract: Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother’s breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N’ terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912142/ doi: 10.1371/journal.pone.0157034 id: cord-000182-ni6iyzdn author: He, Zhisong title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features date: 2010-03-11 words: 6037.0 sentences: 305.0 pages: flesch: 46.0 cache: ./cache/cord-000182-ni6iyzdn.txt txt: ./txt/cord-000182-ni6iyzdn.txt summary: title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features Many researchers have made lots of efforts to develop useful algorithms and softwares to investigate various drug-related biological problems, such as HIV protease cleavage site prediction [18, 19] , identification of GPCR (G protein-coupled receptors) type [20, 21] , protein signal peptide prediction [22] , protein subcellular location prediction [23, 24, 25] , analysis of specificity of GalNAc-transferase protein [26] , identification of protease type [27, 28] , membrane protein type prediction [29, 30, 31, 32] , and a series of relevant webserver predictors as summarized in a recent review [33] . The drug-target benchmark datasets thus obtained for enzymes, ion-channels, GPCRs, and nuclear receptors are given in Online Supporting Information S1, S2, S3, and S4, respectively. Prediction of G-protein-coupled receptor classes based on the concept of Chou''s pseudo amino acid composition: an approach from discrete wavelet transform abstract: BACKGROUND: Study of drug-target interaction networks is an important topic for drug development. It is both time-consuming and costly to determine compound-protein interactions or potential drug-target interactions by experiments alone. As a complement, the in silico prediction methods can provide us with very useful information in a timely manner. METHODS/PRINCIPAL FINDINGS: To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties. The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method. Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G-protein- coupled receptors and nuclear receptors. Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups. As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively. CONCLUSION/SIGNIFICANCE: Our results indicate that the network prediction system thus established is quite promising and encouraging. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836373/ doi: 10.1371/journal.pone.0009603 id: cord-325282-20l9xcmg author: Helal, Mohamed A. title: Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia date: 2020-09-16 words: 6739.0 sentences: 365.0 pages: flesch: 53.0 cache: ./cache/cord-325282-20l9xcmg.txt txt: ./txt/cord-325282-20l9xcmg.txt summary: title: Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The entry of the virus into host cells is facilitated by binding of its transmembrane spike (S) protein with angiotensin-converting enzyme 2 (ACE-2) receptor (Hoffmann et al., 2020) . To understand the mechanism of interaction of the SARS-CoV-2 spike protein with the CD147 receptor, we have performed a four-stage in-silico study. The recently reported crystal structure of SARS-Cov-2 spike protein complex with ACE2 (PDB ID: 6LZG) reveals that the virus utilizes the external subdomain of the spike Receptor Binding Domain (RBD) to recognize the human ACE2 receptor . abstract: Lymphopenia is considered one of the most characteristic clinical features of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. Since T lymphocytes display a very low expression level of hACE2, a novel receptor might be involved in the entry of SARS-CoV-2 into T cells. The transmembrane glycoprotein CD147 is highly expressed by activated T lymphocytes, and was recently proposed as a probable route for SARS-CoV-2 invasion. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The results showed that this binding is dominated by electrostatic interactions involving residues Arg403, Asn481, and the backbone of Gly502. The overall binding arrangement shows the CD147 C-terminal domain interacting with the spike external subdomain in the grove between the short antiparallel β strands, β1’ and β2’, and the small helix α1’. This proposed interaction was further confirmed using MD simulation and binding free energy calculation. These data contribute to a better understanding of the mechanism of infection of SARS-CoV-2 to T lymphocytes and could provide valuable insights for the rational design of adjuvant treatment for COVID-19. Communicated by Ramaswamy H. Sarma url: https://www.ncbi.nlm.nih.gov/pubmed/32936048/ doi: 10.1080/07391102.2020.1822208 id: cord-316258-7hucqcaj author: Henriques, Elsa S title: Modeling of the Toll-like receptor 3 and a putative Toll-like receptor 3 antagonist encoded by the African swine fever virus date: 2011-01-28 words: 4079.0 sentences: 181.0 pages: flesch: 48.0 cache: ./cache/cord-316258-7hucqcaj.txt txt: ./txt/cord-316258-7hucqcaj.txt summary: A recently identified novel ASFV viral protein (pI329L) was found to inhibit the Toll-like receptor 3 (TLR3) signaling pathway, TLR3 being a crucial "danger detector." pI329L has been predicted to be a transmembrane protein containing extracellular putative leucine-rich repeats similar to TLR3, suggesting that pI329L might act as a TLR3 decoy. As this later domain shares only remote sequence relationships with the available TLR3 templates, a more complex modeling strategy was employed that combines the iterative implementation of (multi)threading/assembly/refinement (I-TASSER) structural prediction with expertise-guided posterior refinement. On dimerization subsequent to recognition of dsRNA, TLR3 recruits the adaptor protein Toll-interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-b (TRIF) to its cytoplasmic domain, thereby initiating a signaling cascade that results in the secretion of type I interferons and other inflammatory cytokines. abstract: African swine fever virus (ASFV) is a large double-stranded DNA virus responsible for a lethal pig disease, to which no vaccine has ever been obtained. Its genome encodes a number of proteins involved in virus survival and transmission in its hosts, in particular proteins that inhibit signaling pathways in infected macrophages and, thus, interfere with the host's innate immune response. A recently identified novel ASFV viral protein (pI329L) was found to inhibit the Toll-like receptor 3 (TLR3) signaling pathway, TLR3 being a crucial “danger detector.” pI329L has been predicted to be a transmembrane protein containing extracellular putative leucine-rich repeats similar to TLR3, suggesting that pI329L might act as a TLR3 decoy. To explore this idea, we used comparative modeling and other structure prediction protocols to propose (a) a model for the TLR3–Toll-interleukin-1 receptor homodimer and (b) a structural fold for pI329L, detailed at atomistic level for its cytoplasmic domain. As this later domain shares only remote sequence relationships with the available TLR3 templates, a more complex modeling strategy was employed that combines the iterative implementation of (multi)threading/assembly/refinement (I-TASSER) structural prediction with expertise-guided posterior refinement. The final pI329L model presents a plausible fold, good structural quality, is consistent with the available experimental data, and it corroborates our hypothesis of pI329L being a TLR3 antagonist. url: http://europepmc.org/articles/pmc3048410?pdf=render doi: 10.1002/pro.554 id: cord-001726-d7iwkatn author: Henry, Kevin A. title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold date: 2015-08-04 words: 10444.0 sentences: 516.0 pages: flesch: 39.0 cache: ./cache/cord-001726-d7iwkatn.txt txt: ./txt/cord-001726-d7iwkatn.txt summary: Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage''s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage''s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. While in some cases the results of these studies have been promising, antibody epitope-based peptide vaccines are no longer an area of active research for several reasons: (i) in many cases, peptides incompletely or inadequately mimic epitopes on folded proteins (Irving et al., 2010 ; see below); (ii) antibodies against a single epitope may be of limited utility, especially for highly variable pathogens (Van Regenmortel, 2012); and (iii) for pathogens for which protective immune responses are generated efficiently during natural infection, peptide vaccines offer few advantages over recombinant subunit and live vector vaccines, which have become easier to produce over time. abstract: For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage’s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage’s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523942/ doi: 10.3389/fmicb.2015.00755 id: cord-254107-02bik024 author: Hillisch, Alexander title: Utility of homology models in the drug discovery process date: 2004-08-31 words: 7374.0 sentences: 374.0 pages: flesch: 43.0 cache: ./cache/cord-254107-02bik024.txt txt: ./txt/cord-254107-02bik024.txt summary: The quality of these homology models, and thus their applicability to, for example, drug discovery, predominantly depends on the sequence similarity between the protein of known structure (template) and the protein to be modeled (target). In conjunction with homology models, Cengent Therapeutics (http://www.cengent.com) offers dynamic structural information generated from molecular dynamics simulations for 5500 human drug target proteins. If sequence identity is greater than ~50%, the resulting models are frequently of sufficient quality to be used in the prediction of detailed protein-ligand interactions, such as structure-based drug design and prediction of the preferred sites of metabolism of small molecules ( Figure 2 ). It has recently been shown that it is possible to design small molecules based on homology models and then to use these compounds as tools to study the physiological role of the respective target protein of that particular drug [31] . abstract: Abstract Advances in bioinformatics and protein modeling algorithms, in addition to the enormous increase in experimental protein structure information, have aided in the generation of databases that comprise homology models of a significant portion of known genomic protein sequences. Currently, 3D structure information can be generated for up to 56% of all known proteins. However, there is considerable controversy concerning the real value of homology models for drug design. This review provides an overview of the latest developments in this area and includes selected examples of successful applications of the homology modeling technique to pharmaceutically relevant questions. In addition, the strengths and limitations of the application of homology models during all phases of the drug discovery process are discussed. url: https://api.elsevier.com/content/article/pii/S1359644604031964 doi: 10.1016/s1359-6446(04)03196-4 id: cord-296928-wu14k7u9 author: Hofmann, Tim title: Greatest Hits—Innovative Technologies for High Throughput Identification of Bispecific Antibodies date: 2020-09-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Recent years have shown a tremendous increase and diversification in antibody-based therapeutics with advances in production techniques and formats. The plethora of currently investigated bi- to multi-specific antibody architectures can be harnessed to elicit a broad variety of specific modes of actions in oncology and immunology, spanning from enhanced selectivity to effector cell recruitment, all of which cannot be addressed by monospecific antibodies. Despite continuously growing efforts and methodologies, the identification of an optimal bispecific antibody as the best possible combination of two parental monospecific binders, however, remains challenging, due to tedious cloning and production, often resulting in undesired extended development times and increased expenses. Although automated high throughput screening approaches have matured for pharmaceutical small molecule development, it was only recently that protein bioconjugation technologies have been developed for the facile generation of bispecific antibodies in a ‘plug and play’ manner. In this review, we provide an overview of the most relevant methodologies for bispecific screening purposes—the DuoBody concept, paired light chain single cell production approaches, Sortase A and Transglutaminase, the SpyTag/SpyCatcher system, and inteins—and elaborate on the benefits as well as drawbacks of the different technologies. url: https://doi.org/10.3390/ijms21186551 doi: 10.3390/ijms21186551 id: cord-000979-cav9n18w author: Hoppe, Sebastian title: Rapid Identification of Novel Immunodominant Proteins and Characterization of a Specific Linear Epitope of Campylobacter jejuni date: 2013-05-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Campylobacter jejuni remains one of the major gut pathogens of our time. Its zoonotic nature and wide-spread distribution in industrialized countries calls for a quick and reliable diagnostic tool. Antibody-based detection presents a suitable means to identify pathogenic bacteria. However, the knowledge about immunodominant targets is limited. Thus, an approach is presented, which allows for the rapid screening of numerous cDNA derived expression clones to identify novel antigens. The deeper understanding of immunodominant proteins assists in the design of diagnostic tools and furthers the insight into the bacterium’s pathogenicity as well as revealing potential candidates for vaccination. We have successfully screened 1536 clones of an expression library to identify 22 proteins that have not been described as immunodominant before. After subcloning the corresponding 22 genes and expression of full-length proteins, we investigated the immunodominant character by microarrays and ELISA. Subsequently, seven proteins were selected for epitope mapping. For cj0669 and cj0920c linear epitopes were identified. For cj0669, specificity assays revealed a specific linear epitope site. Consequently, an eleven amino acid residue sequence TLIKELKRLGI was analyzed via alanine scan, which revealed the glycine residue to be significant for binding of the antibody. The innovative approach presented herein of generating cDNAs of prokaryotes in combination with a microarray platform rendering time-consuming purification steps obsolete has helped to illuminate novel immunodominant proteins of C.jejuni. The findings of a specific linear epitope pave the way for a plethora of future research and the potential use in diagnostic applications such as serological screenings. Moreover, the current approach is easily adaptable to other highly relevant bacteria making it a formidable tool for the future discovery of antigens and potential biomarkers. Consequently, it is desirable to simplify the identification of structural epitopes, as this would extend the spectrum of novel epitopes to be detected. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667084/ doi: 10.1371/journal.pone.0065837 id: cord-001435-ebl8yc92 author: Hoppe, Sebastian title: Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae date: 2014-10-21 words: 9619.0 sentences: 545.0 pages: flesch: 50.0 cache: ./cache/cord-001435-ebl8yc92.txt txt: ./txt/cord-001435-ebl8yc92.txt summary: Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen. Incubation with antibodies reactive to either of those two bacterial species resulted in signal intensities in the neighbourhood of the negative control independent of sequence alterations, see Figure 11 . In contrast, the other two proteins displaying linear epitopes, KPN_00363 and KPN_00459, indicated some specificity with the antibodies tested and two linear consensus sequences could be derived, GAVVALSTTFA and GIAFGAVELFD, respectively. abstract: The continuous expansion of nosocomial infections around the globe has become a precarious situation. Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases. Thus, new ways to rapidly detect these infections are vital. Consequently, researchers around the globe pursue innovative approaches for point-of-care devices. In many cases the specific interaction of an antigen and a corresponding antibody is pivotal. However, the knowledge about suitable antigens is lacking. The aim of this study was to identify novel antigens as specific diagnostic markers. Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options. Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After screening 1536 clones, 14 previously unknown immunogenic proteins were identified. Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses. Consequently, six proteins were selected for epitope mapping and three thereof possessed linear epitopes. After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae. The remaining epitopes showed ambiguous results regarding the specificity for K. pneumoniae. The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before. Now, we have transferred this knowledge to the key nosocomial agent, K. pneumoniae. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205017/ doi: 10.1371/journal.pone.0110703 id: cord-261375-6fu3dzi9 author: Hoppe, Sebastian title: Microarray-based method for screening of immunogenic proteins from bacteria date: 2012-03-21 words: 6693.0 sentences: 389.0 pages: flesch: 51.0 cache: ./cache/cord-261375-6fu3dzi9.txt txt: ./txt/cord-261375-6fu3dzi9.txt summary: Screening of expression libraries to expose novel antigens from bacteria often lead to an abundance of false positive signals owing to the high cross reactivity of polyclonal antibodies towards the proteins of the expression host. In this paper, we describe a method to covalently attach different HaloTag ® fusion proteins on HaloLink™ slides (see Figure 1 ) and consequently perform an immunoscreening using polyclonal antibodies in a microarray format, which is a suitable method for high-throughput applications such as screening of entire expression libraries (see Figure 2 ). Using our new method, we were able to express, immobilize and screen all of nine different proteins from Campylobacter jejuni using HaloTag ® and KRX cells. We were able to clone several genes from Campylobacter jejuni into KRX cells, to express the respective proteins as fusion constructs with a HaloTag ® attached to their N-Terminus and to immobilize these proteins on microarray surfaces. abstract: BACKGROUND: Detection of immunogenic proteins remains an important task for life sciences as it nourishes the understanding of pathogenicity, illuminates new potential vaccine candidates and broadens the spectrum of biomarkers applicable in diagnostic tools. Traditionally, immunoscreenings of expression libraries via polyclonal sera on nitrocellulose membranes or screenings of whole proteome lysates in 2-D gel electrophoresis are performed. However, these methods feature some rather inconvenient disadvantages. Screening of expression libraries to expose novel antigens from bacteria often lead to an abundance of false positive signals owing to the high cross reactivity of polyclonal antibodies towards the proteins of the expression host. A method is presented that overcomes many disadvantages of the old procedures. RESULTS: Four proteins that have previously been described as immunogenic have successfully been assessed immunogenic abilities with our method. One protein with no known immunogenic behaviour before suggested potential immunogenicity. We incorporated a fusion tag prior to our genes of interest and attached the expressed fusion proteins covalently on microarrays. This enhances the specific binding of the proteins compared to nitrocellulose. Thus, it helps to reduce the number of false positives significantly. It enables us to screen for immunogenic proteins in a shorter time, with more samples and statistical reliability. We validated our method by employing several known genes from Campylobacter jejuni NCTC 11168. CONCLUSIONS: The method presented offers a new approach for screening of bacterial expression libraries to illuminate novel proteins with immunogenic features. It could provide a powerful and attractive alternative to existing methods and help to detect and identify vaccine candidates, biomarkers and potential virulence-associated factors with immunogenic behaviour furthering the knowledge of virulence and pathogenicity of studied bacteria. url: https://www.ncbi.nlm.nih.gov/pubmed/22436172/ doi: 10.1186/1477-3155-10-12 id: cord-010776-ura14oci author: Hosseini, Elahe Seyed title: Optimization and One-Step Purification of Recombinant V Antigen Production from Yersinia pestis date: 2020-01-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The purpose of this study was to develop an efficient and inexpensive method for the useful production of recombinant protein V antigen, an important virulence factor for Yersinia pestis. To this end, the synthetic gene encoding the V antigen was subcloned into the downstream of the intein (INT) and chitin-binding domain (CBD) from the pTXB1 vector using specific primers. In the following, the produced new plasmid, pTX-V, was transformed into E. coli ER(2566) strain, and the expression accuracy was confirmed using electrophoresis and Western blotting. In addition, the effects of medium, inducer, and temperature on the enhancement of protein production were studied using the Taguchi method. Finally, the V antigen was purified by a chitin affinity column using INT and CBD tag. The expression was induced by 0.05 mM IPTG at 25 °C under optimal conditions including TB medium. It was observed that the expression of the V-INT–CBD fusion protein was successfully increased to more than 40% of the total protein. The purity of V antigen was as high as 90%. This result indicates that V antigen can be produced at low cost and subjected to one-step purification using a self-cleaving INT tag. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222043/ doi: 10.1007/s12033-019-00234-x id: cord-314039-qkrmxvaj author: Houdebine, Louis-Marie title: Production of pharmaceutical proteins by transgenic animals date: 2008-02-19 words: 4773.0 sentences: 278.0 pages: flesch: 47.0 cache: ./cache/cord-314039-qkrmxvaj.txt txt: ./txt/cord-314039-qkrmxvaj.txt summary: Interestingly, genetically modified yeast expressing foreign genes coding for enzymes responsible for glycosylation proved able to secrete substantial amounts of recombinant proteins having carbohydrates almost similar to those found in human proteins [1] . Transgenic animals offer particularly attractive possibilities to prepare recombinant pharmaceutical proteins. Ruminants are potentially the most appropriate species to produce large amount of proteins but they need cloning or lentiviral vectors to integrate foreign genes, their reproduction is relatively slow, they do not glycosylate proteins as well as rabbits and pigs and they are sensitive to prion diseases (Tables 3 and 4) . The recombinant protein ATryn (human antithrombinIII) produced in goat milk contains less sialic acid than its native counterpart is a case in point [29] . The two major animal systems to produce pharmaceutical proteins in milk and egg white have recently been technically improved and their use as an essential source of new medicaments has become very likely. abstract: Proteins started being used as pharmaceuticals in the 1920s with insulin extracted from pig pancreas. In the early 1980s, human insulin was prepared in recombinant bacteria and it is now used by all patients suffering from diabetes. Several other proteins and particularly human growth hormone are also prepared from bacteria. This success was limited by the fact that bacteria cannot synthesize complex proteins such as monoclonal antibodies or coagulation blood factors which must be matured by post-translational modifications to be active or stable in vivo. These modifications include mainly folding, cleavage, subunit association, γ-carboxylation and glycosylation. They can be fully achieved only in mammalian cells which can be cultured in fermentors at an industrial scale or used in living animals. Several transgenic animal species can produce recombinant proteins but presently two systems started being implemented. The first is milk from farm transgenic mammals which has been studied for 20 years and which allowed a protein, human antithrombin III, to receive the agreement from EMEA (European Agency for the Evaluation of Medicinal Products) to be put on the market in 2006. The second system is chicken egg white which recently became more attractive after essential improvement of the methods used to generate transgenic birds. Two monoclonal antibodies and human interferon-β1a could be recovered from chicken egg white. A broad variety of recombinant proteins were produced experimentally by these systems and a few others. This includes monoclonal antibodies, vaccines, blood factors, hormones, growth factors, cytokines, enzymes, milk proteins, collagen, fibrinogen and others. Although these tools have not yet been optimized and are still being improved, a new era in the production of recombinant pharmaceutical proteins was initiated in 1987 and became a reality in 2006. In the present review, the efficiency of the different animal systems to produce pharmaceutical proteins are described and compared to others including plants and micro-organisms. url: https://www.ncbi.nlm.nih.gov/pubmed/18243312/ doi: 10.1016/j.cimid.2007.11.005 id: cord-264996-og3sg0qw author: Howell, Gareth J. title: Cell Biology of Membrane Trafficking in Human Disease date: 2006-09-17 words: 20320.0 sentences: 1072.0 pages: flesch: 42.0 cache: ./cache/cord-264996-og3sg0qw.txt txt: ./txt/cord-264996-og3sg0qw.txt summary: Many of these transport intermediates or vesicles, whether derived from the ER, other internal organelles, or the plasma membrane, are ''''coated'''' with unique protein complexes, tethering factors, and regulatory factors that ensure correct targeting to an acceptor compartment. Breast cancer Caveolin-1 Deletion or dominant negative mutation of caveolin-1 promotes tumor progression Breast cancer (Bouras et al., 2004; Williams and Lisanti, 2005) (Hayasaka et al., 1993; Matsuyama et al., 2002) Chediak-Higashi syndrome (CHS) CHS1/Lyst Lyst involved in regulation of protein secretion from lysosomes -enlarged lysosomes Partial albinism, recurrent bacterial infections, impaired chemotaxis and abnormal natural killer cell function (Shiflett et al., 2002; Ward et al., 2003) 214500 Choroideremia (CHM) Rab Escort Protein 1 (REP1) RAB27a remains cytosolic due to defective geranylgeranyl modification in CHM lymphoblasts X-linked form of retinal degeneration 303100 Various mechanisms control the traYcking of proteins from the TGN by the formation and delivery of membrane-derived transport vesicles to the plasma membrane, endosomes, or lysosomal structures (Ponnambalam and Baldwin, 2003) . abstract: Understanding the molecular and cellular mechanisms underlying membrane traffic pathways is crucial to the treatment and cure of human disease. Various human diseases caused by changes in cellular homeostasis arise through a single gene mutation(s) resulting in compromised membrane trafficking. Many pathogenic agents such as viruses, bacteria, or parasites have evolved mechanisms to subvert the host cell response to infection, or have hijacked cellular mechanisms to proliferate and ensure pathogen survival. Understanding the consequence of genetic mutations or pathogenic infection on membrane traffic has also enabled greater understanding of the interactions between organisms and the surrounding environment. This review focuses on human genetic defects and molecular mechanisms that underlie eukaryote exocytosis and endocytosis and current and future prospects for alleviation of a variety of human diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/16984815/ doi: 10.1016/s0074-7696(06)52005-4 id: cord-262585-5vjqrnwh author: Hraber, Peter title: Resources to Discover and Use Short Linear Motifs in Viral Proteins date: 2019-08-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Motif mimicry tolerates mutations, evolves quickly to modify interactions with the host, and enables modular interactions with protein complexes. Host cells cannot easily coordinate changes to conserved motif recognition and binding interfaces under selective pressure to maintain critical signaling pathways. SLiMs offer potential for use in synthetic biology, such as better immunogens and therapies, but may also present biosecurity challenges. We survey viral uses of SLiMs to mimic host proteins, and information resources available for motif discovery. As the number of examples continues to grow, knowledge management tools are essential to help organize and compare new findings. url: https://www.ncbi.nlm.nih.gov/pubmed/31427097/ doi: 10.1016/j.tibtech.2019.07.004 id: cord-001898-ntqyjqqk author: Huang, Chih-Wei title: Lys-315 at the Interfaces of Diagonal Subunits of δ-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly date: 2016-01-05 words: 6578.0 sentences: 337.0 pages: flesch: 47.0 cache: ./cache/cord-001898-ntqyjqqk.txt txt: ./txt/cord-001898-ntqyjqqk.txt summary: The changes in tryptophan fluorescence were Dilution of monomeric K315A mutant protein denatured in 5 M GdmCl resulted in refolding to a similar conformation as the original monomeric state (Fig 5A and 5B) . Since refolding of partly unfolded monomeric mutant δ-crystallin resulted in a conformation with high exposure of hydrophobic regions, the occurrence of protein aggregation in the process was determined using light scattering measurement. An increase in fluorescence intensity resulting from binding of ThT with the aggregates over time was observed following dilution of 0.84 and 3 M GdmCl denatured monomeric mutant δ-crystallin into buffer (Fig 6B) . The unique stable conformation from unfolding of K315A mutant protein in the presence of urea suggests that the interactions provided by this residue at the interfaces may play a critical role in stabilization of the quaternary structure of δ-crystallin. abstract: δ-Crystallin is the major structural protein in avian eye lenses and is homologous to the urea cycle enzyme argininosuccinate lyase. This protein is structurally assembled as double dimers. Lys-315 is the only residue which is arranged symmetrically at the diagonal subunit interfaces to interact with each other. This study found that wild-type protein had both dimers and monomers present in 2–4 M urea whilst only monomers of the K315A mutant were observed under the same conditions, as judged by sedimentation velocity analysis. The assembly of monomeric K315A mutant was reversible in contrast to wild-type protein. Molecular dynamics simulations showed that the dissociation of primary dimers is prior to the diagonal dimers in wild-type protein. These results suggest the critical role of Lys-315 in stabilization of the diagonal dimer structure. Guanidinium hydrochloride (GdmCl) denatured wild-type or K315A mutant protein did not fold into functional protein. However, the urea dissociated monomers of K315A mutant protein in GdmCl were reversible folding through a multiple steps mechanism as measured by tryptophan and ANS fluorescence. Two partly unfolded intermediates were detected in the pathway. Refolding of the intermediates resulted in a conformation with greater amounts of hydrophobic regions exposed which was prone to the formation of protein aggregates. The formation of aggregates was not prevented by the addition of α-crystallin. These results highlight that the conformational status of the monomers is critical for determining whether reversible oligomerization or aggregate formation occurs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701392/ doi: 10.1371/journal.pone.0145957 id: cord-319291-6l688krc author: Hung, Chun-Min title: Alignment using genetic programming with causal trees for identification of protein functions date: 2006-09-01 words: 8941.0 sentences: 632.0 pages: flesch: 52.0 cache: ./cache/cord-319291-6l688krc.txt txt: ./txt/cord-319291-6l688krc.txt summary: Particularly, the model has three characteristics: (i) it is a hybrid evolutionary model with multiple fitness functions that uses genetic programming to predict protein functions on a distantly related protein family, (ii) it incorporates modified robust point matching to accurately compare all feature points using the moment invariant and thin-plate spline theorems, and (iii) the hierarchical homologies holding up a novel protein sequence in the form of a causal tree can effectively demonstrate the relationship between proteins. The hybrid model, namely Alignment using Genetic programming with Causal Tree (AGCT), is a heuristic evolutionary method that contains three basic components: (i) genetic programming with innerexchanged individual strategy, (ii) causal trees [4, 28, 31] with probabilistic reasoning, and (iii) construction of hierarchical homologies with local block-to-block alignment using the methods of moment invariant and robust points matching (RPM) [24] . abstract: A hybrid evolutionary model is used to propose a hierarchical homology of protein sequences to identify protein functions systematically. The proposed model offers considerable potentials, considering the inconsistency of existing methods for predicting novel proteins. Because some novel proteins might align without meaningful conserved domains, maximizing the score of sequence alignment is not the best criterion for predicting protein functions. This work presents a decision model that can minimize the cost of making a decision for predicting protein functions using the hierarchical homologies. Particularly, the model has three characteristics: (i) it is a hybrid evolutionary model with multiple fitness functions that uses genetic programming to predict protein functions on a distantly related protein family, (ii) it incorporates modified robust point matching to accurately compare all feature points using the moment invariant and thin-plate spline theorems, and (iii) the hierarchical homologies holding up a novel protein sequence in the form of a causal tree can effectively demonstrate the relationship between proteins. This work describes the comparisons of nucleocapsid proteins from the putative polyprotein SARS virus and other coronaviruses in other hosts using the model. url: https://www.sciencedirect.com/science/article/pii/S0362546X05009028 doi: 10.1016/j.na.2005.09.048 id: cord-013178-li1x1m25 author: Hung, Ling-Chu title: The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells date: 2020-08-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The purpose of this study in the context of the open reading frame 3 (ORF3) protein of porcine circovirus type 2 (PCV2) was especially its location and its relation to the capsid protein and the apoptosis protein in PCV2-infected porcine peripheral blood mononuclear cells (PBMCs). To detect the ORF3 protein, monoclonal antibodies (mAbs) were generated in this study. The mAb 7D3 binds to the ORF3 peptide (residues 35–66) and the native ORF3 protein in PCV2-infected PBMCs, as shown by immunofluorescence assay (IFA). The data show that 3–5% of PBMCs were positive for ORF3 protein or p53 protein. Further, 78–82% of PBMCs were positive for the capsid. This study confirmed the ORF3 protein not only colocalized with the capsid protein but also colocalized with the p53 protein in PBMCs. Immunoassays were conducted in this study to detect the capsid protein, the ORF3 protein, anti-capsid IgG, and anti-ORF3 IgG. The data show the correlation (r = 0.758) of the ORF3 protein and the capsid protein in the blood samples from the PCV2-infected herd. However, each anti-viral protein IgG had a different curve of the profile in the same herd after vaccination. Overall, this study provides a blueprint to explore the ORF3 protein in PCV2-infected PBMCs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551997/ doi: 10.3390/v12090961 id: cord-308043-h0knm8y4 author: Hussey, Séamus title: Autophagy as an emerging dimension to adaptive and innate immunity date: 2009-08-31 words: 6905.0 sentences: 378.0 pages: flesch: 37.0 cache: ./cache/cord-308043-h0knm8y4.txt txt: ./txt/cord-308043-h0knm8y4.txt summary: These lines of evidence suggest a more elaborate TLR control of autophagy whereby TLR-adapter molecules interact with proteins from the autophagic pathway rather than by simply activating the classic hierarchical signaling cascades described heretofore. The authors demonstrated that the Atg5-Atg12 conjugate negatively regulates the antiviral immune response by interacting with the RIG-I-like receptor (s protein retinoic acid-inducible gene I (RIG-I) and IFN-␤ promoter stimulator 1 (IPS-1) thus, implying autophagy contributes to viral replication. In another study, the same group demonstrated that the fusion of influenza matrix protein 1 (MP1) with Atg8/LC3 drives this molecule to autophagosomes in different cell types and enhances recognition by antigen specific CD4+ T cells [117] . Accordingly, Atg6 silencing dampened this process, while rapamycin treatment enhanced priming of 85B-specific CD4 + T cells, strongly suggesting a role for autophagy in MHC class II presentation of antigens of bacterial origin. abstract: Abstract Autophagy is an evolutionary conserved cellular process during which cytoplasmic material is engulfed in double membrane vacuoles that then fuse with lysosomes, ultimately degrading their cargo. Emerging evidence, however, now suggests that autophagy can form part of our innate and adaptive immune defense programs. Recent studies have identified pattern recognition molecules as mediators of this process and shown that intracellular pathogens can interact with and even manipulate autophagy. Recent translational evidence has also implicated autophagy in the pathogenesis of several immune-mediated diseases, including Crohn disease. In this review, we present autophagy in the context of its role as an immune system component and effector and speculate on imminent and future research directions in this field. url: https://doi.org/10.1016/j.smim.2009.05.004 doi: 10.1016/j.smim.2009.05.004 id: cord-322231-jltk42dt author: Huy, Nguyen-Xuan title: Immunogenicity of an S1D epitope from porcine epidemic diarrhea virus and cholera toxin B subunit fusion protein transiently expressed in infiltrated Nicotiana benthamiana leaves date: 2016-08-23 words: 6951.0 sentences: 391.0 pages: flesch: 60.0 cache: ./cache/cord-322231-jltk42dt.txt txt: ./txt/cord-322231-jltk42dt.txt summary: title: Immunogenicity of an S1D epitope from porcine epidemic diarrhea virus and cholera toxin B subunit fusion protein transiently expressed in infiltrated Nicotiana benthamiana leaves After oral administration of transiently expressed CTB–S1D fusion protein, or with bacterial cholera toxin or rice callus expressing mutant cholera toxin 61F, mice exhibited significantly greater serum IgG and sIgA levels against bacterial CTB and S1D antigen, peaking at week 6. For feeding immunization, the mice were fasted 8 h before gavage with 2.0 mL of PBS buffer pH 7.0 containing lyophilized leaf powder, which harbored 100 µg of CTB-S1D fusion protein, or with bacterial cholera toxin-bCT (Sigma) or rice callus-expressed mutant cholera toxin 61 F (Arg to Phe)-rCTX and wild-type (WT) N. Oral immunization with transient expression CTB-S1D fusion protein induced significantly higher anti-CTB, anti-S1D IgG and sIgA levels compared with the control group (Fig. 7 ). abstract: Porcine epidemic diarrhea virus (PEDV) belongs to the Coronaviridae family and causes acute enteritis in pigs. A fragment of the large spike glycoprotein, termed the S1D epitope (aa 636–789), alone and fused with cholera toxin B subunit, were independently cloned into plant expression vectors, yielding plasmids pMYV717 and pMYV719, respectively. Plant expression vectors were transformed into Agrobacterium tumefaciens and subsequently infiltrated into Nicotiana benthamiana leaves. The highest expression level of S1D was found at 2 days post infiltration (dpi), reached 0.04 % of total soluble protein, and rapidly decreased thereafter. The expression and assembly of CTB–S1D fusion protein were confirmed by Western blot and G(M1)-ELISA. The highest expression level of CTB–S1D fusion protein was 0.07 % of TSP at 4 dpi, with a rapid decrease thereafter. In the presence of p19 protein from tomato bushy stunt virus, the S1D and CTB–S1D protein levels peaked at 6 dpi and were fourfold to sevenfold higher than in the absence of p19, respectively. After oral administration of transiently expressed CTB–S1D fusion protein, or with bacterial cholera toxin or rice callus expressing mutant cholera toxin 61F, mice exhibited significantly greater serum IgG and sIgA levels against bacterial CTB and S1D antigen, peaking at week 6. Transiently expressed CTB–S1D fusion protein will be administered orally to pigs to assess the immune response against PEDV. url: https://www.ncbi.nlm.nih.gov/pubmed/32214565/ doi: 10.1007/s11240-016-1059-5 id: cord-259260-qcfgigga author: Ibrahim, Ibrahim M. title: GRP78: A cell''s response to stress date: 2019-06-01 words: 6837.0 sentences: 393.0 pages: flesch: 50.0 cache: ./cache/cord-259260-qcfgigga.txt txt: ./txt/cord-259260-qcfgigga.txt summary: GRP78 expression is increased in cases of ER stressors like when the cell is abridged from sugar, treated with reagents that inhibit the process of protein glycosylation or disturb the intercellular calcium storage [5] . In the standard conditions of balance in the cell (homeostasis) GRP78 is bounded in an inactive form to Activating transcription factor 6 (ATF6), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and Inositol-requiring enzyme 1 (IRE1) which are UPR transmembrane stress sensors. According to the ligand or the peptide that bind to CS-GRP78, it will be activated in a defined signaling pathway that affects Besides, if the cell is cancerous, CS GRP78 will induce resistance to chemotherapy. Glucose regulated protein 78 (GRP78) inhibits apoptosis and attentinutes chemosensitivity of gemcitabine in breast cancer cell via AKT/mitochondrial apoptotic pathway De-regulation of GRP stress protein expression in human breast cancer cell lines Kringle 5 of human plasminogen induces apoptosis of endothelial and tumor cells through surface-expressed glucose-regulated protein 78 abstract: Abstract Background Glucose-Regulated Protein 78 (GRP78) is a chaperone heat shock protein that has been intensely studied in the last two decades. GRP78 is the master of the unfolded protein response (UBR) in the Endoplasmic Reticulum (ER) in normal cells. GRP78 force the unfolded proteins to refold or degrade using cellular degradation mechanisms. Scope Under stress, the overexpression of GRP78 on the cell membrane mediates the vast amount of disordered proteins. Unfortunately, this makes it a tool for pathogens (bacterial, fungal and viral) to enter the cell and to start different pathways leading to pathogenesis. Additionally, GRP78 is overexpressed on the membranes of various cancer cells and increase the aggressiveness of the disease. Major conclusions The current review summarizes structure, function, and different mechanisms GRP78 mediate in response to normal or stress conditions. General significance GRP78 targeting and possible inhibition mechanisms are also covered in the present review aiming to prevent the virulence of pathogens and cancer. url: https://doi.org/10.1016/j.lfs.2019.04.022 doi: 10.1016/j.lfs.2019.04.022 id: cord-312996-qzu8pkyt author: Iles, R. K. title: A clinical MALDI-ToF Mass spectrometry assay for SARS-CoV-2: Rational design and multi-disciplinary team work. date: 2020-08-22 words: 6845.0 sentences: 375.0 pages: flesch: 51.0 cache: ./cache/cord-312996-qzu8pkyt.txt txt: ./txt/cord-312996-qzu8pkyt.txt summary: Testing limitations, including reagent shortages, remain a bottleneck in the battle to curtail COVID-19 spread in even the wealthiest countries [1, 2] The development of new matrix assisted laser desorption time of flight mass spectrometry (MALDI-ToF MS) diagnostics for SARS-CoV-2 detection is driven by the need for greater diagnostic capacity and alternative applications to complement standard PCR and antibody based diagnostics. Consequently studies where swab samples have been split for simultaneous analysis by RT PCR detection systems of SARS-CoV-2 RNA and by MALDI-ToF mass spectrometry for viral proteins, are compromised [4] . virus grown in vitro and mass spectra of gargle/saliva spiked with culture media from cells infected with SARS-CoV-2: S proteolytic fragments S1 and S2 were seen in all preparations and S2b only in serum free samples. These confirmed PCR-negative gargle samples were analysed by MALDI-ToF mass spectrometry 40 times; the measured peak intensities of which acted as comparative controls to the viral spiked saliva/gargle. abstract: The COVID-19 pandemic caused by the SARS-CoV-2 Coronavirus has stretched national testing capacities to breaking points in almost all countries of the world. The need to rapidly screen vast numbers of a countrys population in order to control the spread of the infection is paramount. However, the logistical requirement for reagent supply (and associated cost) of RT-PCR based testing (the current front-line test) have been hugely problematic. Mass spectrometry-based methods using swab and gargle samples have been reported with promise, but have not approached the task from a systematic analysis of the entire diagnostic process. Here, the pipeline from sample processing, the biological characteristics of the pathogen in human biofluid, the downstream bio- and physical-chemistry and the all-important data processing with clinical interpretation and reporting, are carefully compiled into a single high throughput and reproducible rapid process. Utilizing MALDI-ToF mass spectrometric detection to viral envelope glycoproteins in a systems biology - multidisciplinary team approach, we have achieved a multifaceted clinical MALDI ToF MS screening test, primarily (but not limited to) SARS-CoV-2, with direct applicable to other future epidemics/pandemics that may arise. The clinical information generated not only includes SARS-CoV-2 Coronavirus detection (Spike protein fragments S1, S2b, S2a peaks), but other respiratory viral infections detected as well as an assessment of generalised oral upper respiratory immune response (elevated total Ig light chain peak) and a measure of the viral immune response (elevated intensity of IgA heavy chain peak). The advantages of the method include; 1) ease of sampling, 2) speed of analysis, and much reduced cost of testing. These features reveal the diagnostic utility of MALDI-ToF mass spectrometry as a powerful and economically attractive global solution. url: http://medrxiv.org/cgi/content/short/2020.08.22.20176669v1?rss=1 doi: 10.1101/2020.08.22.20176669 id: cord-268239-neb6xxlf author: Illiano, Anna title: Protein Glycosylation Investigated by Mass Spectrometry: An Overview date: 2020-08-28 words: 9540.0 sentences: 442.0 pages: flesch: 34.0 cache: ./cache/cord-268239-neb6xxlf.txt txt: ./txt/cord-268239-neb6xxlf.txt summary: For example, the alanine-proline-rich antigen (Apa) glycoprotein, expressed on the cell surface of different Mycobacteria species, induced glycan-specific T-cell response, whereas the non-glycosylated form of the same protein in Escherichia coli showed reduced stimulation of the CD4 + T-cell system compared to the native antigen, giving evidence of the crucial involvement of glycosylation in T-cell activation by Apa during infection [42] . Technological breakthroughs in mass spectrometric analysis for specific glycan epitopes provide a more molecular approach to examine potential changes in glycosylation or to display a sufficient degree of alteration in glycosylation, as mixtures of commonly occurring glycosylation patterns associated with normal cells or tumor-associated signals [82, 84] . abstract: The protein glycosylation is a post-translational modification of crucial importance for its involvement in molecular recognition, protein trafficking, regulation, and inflammation. Indeed, abnormalities in protein glycosylation are correlated with several disease states such as cancer, inflammatory diseases, and congenial disorders. The understanding of cellular mechanisms through the elucidation of glycan composition encourages researchers to find analytical solutions for their detection. Actually, the multiplicity and diversity of glycan structures bond to the proteins, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies make their detection much trickier than other kinds of biopolymers. An overview of the most prominent techniques based on mass spectrometry (MS) for protein glycosylation (glycoproteomics) studies is here presented. The tricks and pre-treatments of samples are discussed as a crucial step prodromal to the MS analysis to improve the glycan ionization efficiency. Therefore, the different instrumental MS mode is also explored for the qualitative and quantitative analysis of glycopeptides and the glycans structural composition, thus contributing to the elucidation of biological mechanisms. url: https://doi.org/10.3390/cells9091986 doi: 10.3390/cells9091986 id: cord-315984-5gbhobw8 author: Isaacson, Marisa K. title: Ubiquitination, Ubiquitin-like Modifiers, and Deubiquitination in Viral Infection date: 2009-06-18 words: 8898.0 sentences: 467.0 pages: flesch: 44.0 cache: ./cache/cord-315984-5gbhobw8.txt txt: ./txt/cord-315984-5gbhobw8.txt summary: HPV infection also leads to degradation of the retinoblastoma protein pRb through the ubiquitin-proteasome pathway (reviewed in Mammas et al., 2008) , mediated via the HPV E7-protein-induced generation of an E3 ligase complex consisting of the Cullin2 Processed ubiquitin (Ub) or ubiquitin-like modifier (Ubl) is activated with ATP by an E1 ubiquitin-activating enzyme (1) and then transferred to an E2 ubiquitin-conjugating enzyme (2). Herpes simplex virus 1 (HSV-1) infected cell protein 0 (ICP0) is a E3 ubiquitin ligase that induces polyubiquitination and degradation of a variety of proteins, including the promyelocytic leukemia (PML) protein, Sp100 (another component of PML nuclear bodies) (Chelbi-Alix and de Boutell et al., 2002) , cyclin D3 (Van Sant et al., 2001; Hagglund et al., 2002) , p53, and the cellular deubiquitinating enzyme USP7. abstract: Ubiquitin is important for nearly every aspect of cellular physiology. All viruses rely extensively on host machinery for replication; therefore, it is not surprising that viruses connect to the ubiquitin pathway at many levels. Viral involvement with ubiquitin occurs either adventitiously because of the unavoidable usurpation of cellular processes, or for some specific purpose selected for by the virus to enhance viral replication. Here, we review current knowledge of how the ubiquitin pathway alters viral replication and how viruses influence the ubiquitin pathway to enhance their own replication. url: https://www.sciencedirect.com/science/article/pii/S1931312809001796 doi: 10.1016/j.chom.2009.05.012 id: cord-304616-k92fa15l author: Izes, Aaron M. title: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats date: 2020-08-05 words: 4208.0 sentences: 234.0 pages: flesch: 50.0 cache: ./cache/cord-304616-k92fa15l.txt txt: ./txt/cord-304616-k92fa15l.txt summary: title: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. Consequently, the aim of this study was two-fold: first, to develop and validate a high pressure liquid chromatography (HPLC) method to detect mefloquine in feline plasma, and second, to determine the in vitro plasma protein binding of mefloquine in both clinically normal and FIP-affected cats. Here, although a significant difference was found between the plasma protein binding of mefloquine in clinically normal and FIP-affected cats, due to the unknown biological variability of the assay, it is likely that this difference is equivocal. This study has validated an accurate and reliable assay to detect mefloquine in feline plasma and demonstrated that mefloquine is highly plasma protein bound in both clinically normal and FIP-affected cats. abstract: The antimalarial agent mefloquine is currently being investigated for its potential to inhibit feline coronavirus and feline calicivirus infections. A simple, high pressure liquid chromatography assay was developed to detect mefloquine plasma concentrations in feline plasma. The assay’s lower limit of quantification was 250 ng/mL. The mean ± standard deviation intra- and inter-day precision expressed as coefficients of variation were 6.83 ± 1.75 and 5.33 ± 1.37%, respectively, whereas intra- and inter-day accuracy expressed as a percentage of the bias were 11.40 ± 3.73 and 10.59 ± 3.88%, respectively. Accordingly, this validated assay should prove valuable for future in vivo clinical trials of mefloquine as an antiviral agent against feline coronavirus and feline calicivirus. However, the proportion of mefloquine binding to feline plasma proteins has not been reported. The proportion of drug bound to plasma protein binding is an important concept when developing drug dosing regimens. As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. An in vitro method using rapid equilibrium dialysis demonstrated that mefloquine was highly plasma protein bound in both populations (on average > 99%). url: https://doi.org/10.1371/journal.pone.0236754 doi: 10.1371/journal.pone.0236754 id: cord-002711-b7mlt19n author: Jacomin, Anne-Claire title: iLIR@viral: A web resource for LIR motif-containing proteins in viruses date: 2017-08-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Macroautophagy/autophagy has been shown to mediate the selective lysosomal degradation of pathogenic bacteria and viruses (xenophagy), and to contribute to the activation of innate and adaptative immune responses. Autophagy can serve as an antiviral defense mechanism but also as a proviral process during infection. Atg8-family proteins play a central role in the autophagy process due to their ability to interact with components of the autophagy machinery as well as selective autophagy receptors and adaptor proteins. Such interactions are usually mediated through LC3-interacting region (LIR) motifs. So far, only one viral protein has been experimentally shown to have a functional LIR motif, leaving open a vast field for investigation. Here, we have developed the iLIR@viral database (http://ilir.uk/virus/) as a freely accessible web resource listing all the putative canonical LIR motifs identified in viral proteins. Additionally, we used a curated text-mining analysis of the literature to identify novel putative LIR motif-containing proteins (LIRCPs) in viruses. We anticipate that iLIR@viral will assist with elucidating the full complement of LIRCPs in viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640201/ doi: 10.1080/15548627.2017.1356978 id: cord-256047-mabrmzd9 author: Jacomin, Anne-Claire title: Deubiquitinating Enzymes Related to Autophagy: New Therapeutic Opportunities? date: 2018-08-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Autophagy is an evolutionary conserved catabolic process that allows for the degradation of intracellular components by lysosomes. This process can be triggered by nutrient deprivation, microbial infections or other challenges to promote cell survival under these stressed conditions. However, basal levels of autophagy are also crucial for the maintenance of proper cellular homeostasis by ensuring the selective removal of protein aggregates and dysfunctional organelles. A tight regulation of this process is essential for cellular survival and organismal health. Indeed, deregulation of autophagy is associated with a broad range of pathologies such as neuronal degeneration, inflammatory diseases, and cancer progression. Ubiquitination and deubiquitination of autophagy substrates, as well as components of the autophagic machinery, are critical regulatory mechanisms of autophagy. Here, we review the main evidence implicating deubiquitinating enzymes (DUBs) in the regulation of autophagy. We also discuss how they may constitute new therapeutic opportunities in the treatment of pathologies such as cancers, neurodegenerative diseases or infections. url: https://doi.org/10.3390/cells7080112 doi: 10.3390/cells7080112 id: cord-328483-sj8i9ss2 author: Jaegle, Mike title: Protein‐Templated Fragment Ligations—From Molecular Recognition to Drug Discovery date: 2017-05-31 words: 9580.0 sentences: 543.0 pages: flesch: 44.0 cache: ./cache/cord-328483-sj8i9ss2.txt txt: ./txt/cord-328483-sj8i9ss2.txt summary: Protein-templated fragment ligations are chemical reactions between small molecules ("fragments") utilizing aproteinss urface as areaction vessel to catalyzethe formation of aprotein ligand with increased binding affinity.T he approache xploits the molecular recognition of reactive small-molecule fragments by proteins both for ligand assembly and for the identification of bioactive fragment combinations.Inthis way, chemical synthesis and bioassayare integrated in one single step.T his Review discusses the biophysical basis of reversible and irreversible fragment ligations and gives an overview of the available methods to detect protein-templated ligation products.T he chemical scope and recent applications as well as future potential of the concept in drug discovery are reviewed. abstract: Protein‐templated fragment ligation is a novel concept to support drug discovery and can help to improve the efficacy of protein ligands. Protein‐templated fragment ligations are chemical reactions between small molecules (“fragments”) utilizing a protein's surface as a reaction vessel to catalyze the formation of a protein ligand with increased binding affinity. The approach exploits the molecular recognition of reactive small‐molecule fragments by proteins both for ligand assembly and for the identification of bioactive fragment combinations. In this way, chemical synthesis and bioassay are integrated in one single step. This Review discusses the biophysical basis of reversible and irreversible fragment ligations and gives an overview of the available methods to detect protein‐templated ligation products. The chemical scope and recent applications as well as future potential of the concept in drug discovery are reviewed. url: https://www.ncbi.nlm.nih.gov/pubmed/28117936/ doi: 10.1002/anie.201610372 id: cord-350423-yaeduwvb author: James, Claire D. title: Viral Interactions with PDZ Domain-Containing Proteins—An Oncogenic Trait? date: 2016-01-18 words: 10615.0 sentences: 433.0 pages: flesch: 39.0 cache: ./cache/cord-350423-yaeduwvb.txt txt: ./txt/cord-350423-yaeduwvb.txt summary: Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ) interaction modules. Survival of rabies infected neuronal cells is associated with the ability of the viral envelope G protein to interact with the PDZ domain-containing serine threonine kinase MAST2, leading to the disruption of the MAST2-PTEN complex that is intimately involved in the inhibition of neuronal survival [11] . Therefore, in HPV infections the tumour suppressor forms of DLG that are involved in the negative regulation of cell proliferation might be the initial target of the E6 PBM, but during disease progression DLG1, either through mislocalization and/or the stabilization of specific pools, acquires oncogenic functions mediated by interaction with E6 [3, 127] . abstract: Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ) interaction modules. In many cases (but not always), the viruses have evolved to bind the PDZ domains using the same short linear peptide motifs found in host protein-PDZ interactions, and in some cases regulate the interactions in a similar fashion by phosphorylation. What is striking is that the diverse viruses target a common subset of PDZ proteins that are intimately involved in controlling cell polarity and the structure and function of intercellular junctions, including tight junctions. Cell polarity is fundamental to the control of cell proliferation and cell survival and disruption of polarity and the signal transduction pathways involved is a key event in tumourigenesis. This review focuses on the oncogenic viruses and the role of targeting PDZ proteins in the virus life cycle and the contribution of virus-PDZ protein interactions to virus-mediated oncogenesis. We highlight how many of the viral associations with PDZ proteins lead to deregulation of PI3K/AKT signalling, benefitting virus replication but as a consequence also contributing to oncogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/26797638/ doi: 10.3390/pathogens5010008 id: cord-308641-vqiipbo8 author: Jankauskaitė, Justina title: SKEMPI 2.0: an updated benchmark of changes in protein–protein binding energy, kinetics and thermodynamics upon mutation date: 2019-02-01 words: 5458.0 sentences: 232.0 pages: flesch: 47.0 cache: ./cache/cord-308641-vqiipbo8.txt txt: ./txt/cord-308641-vqiipbo8.txt summary: Once the checks are passed, the data is collected, including the PDB file, the chains of the interacting subunits, the mutation, the wild-type and mutant affinities (K D , M), the reference, the names of the proteins, the temperature at which the experiment is performed (T, K), the experimental method used (an extension of the category scheme of Geng et al., 2016) , notes on the entry and, when available, the association rate (k on ; M À1 s À1 ), dissociation rate (k off ; s À1 ), enthalpy (DH; kcal:mol À1 ) and entropy (DS; cal:mol À1 :K À1 ). abstract: MOTIVATION: Understanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein–protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering. RESULTS: We present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein–protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations, which abolish detectable binding. AVAILABILITY AND IMPLEMENTATION: The database is available as supplementary data and at https://life.bsc.es/pid/skempi2/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. url: https://www.ncbi.nlm.nih.gov/pubmed/30020414/ doi: 10.1093/bioinformatics/bty635 id: cord-346314-o9fjpqaj author: Jarboui, Mohamed Ali title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus date: 2012-11-15 words: 10004.0 sentences: 521.0 pages: flesch: 36.0 cache: ./cache/cord-346314-o9fjpqaj.txt txt: ./txt/cord-346314-o9fjpqaj.txt summary: Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. Following the detailed annotation of the quantitative abundance changes in the nucleolar protein composition upon Tat expression, we focussed on the Tat-affected cellular complexes and signalling pathways associated with ribosome biogenesis, spliceosome, molecular chaperones, DNA replication and repair and metabolism and discuss their potential involvement in HIV-1 pathogenesis. In this study, we investigated the quantitative changes in the nucleolar proteome of Jurkat T cells constitutively expressing HIV-1 Tat (86aa) versus their Tat-negative counterpart, using stable isotope labelling with amino acids in cell culture (SILAC) technology, followed by ESI tandem mass spectrometry and implemented the experimental approach described in Figure 1A . abstract: The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these proteins collectively participate in interconnected networks converging to adapt the nucleolus dynamic activities, which favor host biosynthetic activities and may contribute to create a cellular environment supporting robust HIV-1 production. url: https://www.ncbi.nlm.nih.gov/pubmed/23166591/ doi: 10.1371/journal.pone.0048702 id: cord-021500-sy6lnt7b author: Jean Harry, G. title: Myelination, Dysmyelination, and Demyelination date: 2007-05-09 words: 17601.0 sentences: 760.0 pages: flesch: 37.0 cache: ./cache/cord-021500-sy6lnt7b.txt txt: ./txt/cord-021500-sy6lnt7b.txt summary: The size of the fibers and the thickness of the sheaths are very different in the PNS and the CNS, but the overall surface area of myelin generated by an oligodendrocyte around multiple axons may be no larger than that formed by a Schwann cell around a single internode. Myelinating Schwann cells progress through a proliferative "premyelinating" stage, characterized by transient expression of suppressed cAMP-inducible Pou-domain transcription factor (SCIP), followed by a "promyelinating" GalC-positive stage, becoming associated with a single axon in the process. Members of the NDF growth factor family, including glial growth factor (GGF), heregulin, acetylcholine-inducing activity (ARIA), and neuregulin, are alternatively spliced products of a single gene, and these molecules are emerging as important regulators of Schwann cell lineage development (Dong et aL, 1995; Zorick and Lemke, 1996) . abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150038/ doi: 10.1016/b978-012648860-9.50007-8 id: cord-283096-qm7h4qui author: Jeon, Young Joo title: ISG15 and immune diseases date: 2010-02-12 words: 11144.0 sentences: 606.0 pages: flesch: 44.0 cache: ./cache/cord-283096-qm7h4qui.txt txt: ./txt/cord-283096-qm7h4qui.txt summary: Some of them are type I IFN-induced proteins, such as PKR and RIG-I, and some are the key regulators that are involved in IFN signaling, such as JAK1 and STAT1, implicating the role of ISG15 and its conjugates in type I IFN-mediated innate immune responses. Viral infection also strongly induces ISG15 [18, 19] because one of its major host responses is the production of type I IFNs. A number of proteins that are involved in antiviral signaling pathways, including RIG-I, MDA-5, Mx1, PKR, STAT1, and JAK1, have been identified as target proteins for ISGylation. Swiss 3T3 cells expressing constitutively active MKK7-JNK1β fusion protein show increased resistance to apoptosis induced by vesicular stomatitis virus (VSV) infection, suggesting the involvement of JNK signaling pathway in antiviral response. acid seems to elevate the levels of ISG15 and its conjugates by stimulating cells to secrete IFNs. UBE1L is a 112-kDa protein that shows a 45% identity in amino acid sequence to the human ubiquitin-activating E1 enzyme (UBE1) [73] . abstract: ISG15, the product of interferon (IFN)-stimulated gene 15, is the first identified ubiquitin-like protein, consisting of two ubiquitin-like domains. ISG15 is synthesized as a precursor in certain mammals and, therefore, needs to be processed to expose the C-terminal glycine residue before conjugation to target proteins. A set of three-step cascade enzymes, an E1 enzyme (UBE1L), an E2 enzyme (UbcH8), and one of several E3 ligases (e.g., EFP and HERC5), catalyzes ISG15 conjugation (ISGylation) of a specific protein. These enzymes are unique among the cascade enzymes for ubiquitin and other ubiquitin-like proteins in that all of them are induced by type I IFNs or other stimuli, such as exposure to viruses and lipopolysaccharide. Mass spectrometric analysis has led to the identification of several hundreds of candidate proteins that can be conjugated by ISG15. Some of them are type I IFN-induced proteins, such as PKR and RIG-I, and some are the key regulators that are involved in IFN signaling, such as JAK1 and STAT1, implicating the role of ISG15 and its conjugates in type I IFN-mediated innate immune responses. However, relatively little is known about the functional significance of ISG15 induction due to the lack of information on the consequences of its conjugation to target proteins. Here, we describe the recent progress made in exploring the biological function of ISG15 and its reversible modification of target proteins and thus in their implication in immune diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/20153823/ doi: 10.1016/j.bbadis.2010.02.006 id: cord-332344-upsn0zb4 author: Jeswin, Joseph title: Proteomic analysis by iTRAQ in red claw crayfish, Cherax quadricarinatus, hematopoietic tissue cells post white spot syndrome virus infection date: 2016-02-01 words: 5882.0 sentences: 285.0 pages: flesch: 42.0 cache: ./cache/cord-332344-upsn0zb4.txt txt: ./txt/cord-332344-upsn0zb4.txt summary: To elucidate proteomic changes of Hpt cells from red claw crayfish, Cherax quadricarinatus, we have carried out isobaric tags for relative and absolute quantitation (iTRAQ) of cellular proteins at both early (1 hpi) and late stage (12 hpi) post white spot syndrome virus (WSSV) infection. Generally, these differentially expressed proteins include: 1) the metabolic process related proteins in glycolysis and glucogenesis, DNA replication, nucleotide/amino acid/fatty acid metabolism and protein biosynthesis; 2) the signal transduction related proteins like small GTPases, G-protein-alpha stimulatory subunit, proteins bearing PDZor 14-3-3-domains that help holding together and organize signaling complexes, casein kinase I and proteins of the MAP-kinase signal transduction pathway; 3) the immune defense related proteins such as α-2 macroglobulin, transglutaminase and trans-activation response RNA-binding protein 1. To further identify proteins or pathways altered during viral infection, here we report proteomic responses of crayfish Hpt cells by iTRAQ at both early (1 hpi) and late (12 hpi) stages post WSSV infection accordingly. abstract: To elucidate proteomic changes of Hpt cells from red claw crayfish, Cherax quadricarinatus, we have carried out isobaric tags for relative and absolute quantitation (iTRAQ) of cellular proteins at both early (1 hpi) and late stage (12 hpi) post white spot syndrome virus (WSSV) infection. Protein database search revealed 594 protein hits by Mascot, in which 17 and 30 proteins were present as differentially expressed proteins at early and late viral infection, respectively. Generally, these differentially expressed proteins include: 1) the metabolic process related proteins in glycolysis and glucogenesis, DNA replication, nucleotide/amino acid/fatty acid metabolism and protein biosynthesis; 2) the signal transduction related proteins like small GTPases, G-protein-alpha stimulatory subunit, proteins bearing PDZ- or 14-3-3-domains that help holding together and organize signaling complexes, casein kinase I and proteins of the MAP-kinase signal transduction pathway; 3) the immune defense related proteins such as α-2 macroglobulin, transglutaminase and trans-activation response RNA-binding protein 1. Taken together, these protein information shed new light on the host cellular response against WSSV infection in a crustacean cell culture. url: https://www.ncbi.nlm.nih.gov/pubmed/26845698/ doi: 10.1016/j.fsi.2016.01.035 id: cord-286217-3uklf2u2 author: Jiang, He-wei title: SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses date: 2020-07-14 words: 6829.0 sentences: 423.0 pages: flesch: 54.0 cache: ./cache/cord-286217-3uklf2u2.txt txt: ./txt/cord-286217-3uklf2u2.txt summary: Here we construct a SARS-CoV-2 proteome microarray containing 18 out of the 28 predicted proteins and apply it to the characterization of the IgG and IgM antibodies responses in the sera from 29 convalescent patients. We detected the SARS-CoV-2-specific IgG and IgM proteins bound to the array using fluorescent-labeled anti-human antibodies, thereby generating a global assessment of each patient''s humoral antibody response. All of the samples and the controls were probed on the proteome microarray, and after data filtering and normalization, we constructed the IgG and IgM profile for each serum and performed clustering analysis to generate heatmaps (Figs. To statistically analyze the IgG responses against SARS-CoV-2 proteins, we calculated the p-values followed by multiple testing correction (or q-values), and applied significant analysis of microarray (SAM) to identify significant positive proteins (Supplementary Fig. 7 and Data 2). abstract: We still know very little about how the human immune system responds to SARS-CoV-2. Here we construct a SARS-CoV-2 proteome microarray containing 18 out of the 28 predicted proteins and apply it to the characterization of the IgG and IgM antibodies responses in the sera from 29 convalescent patients. We find that all these patients had IgG and IgM antibodies that specifically bind SARS-CoV-2 proteins, particularly the N protein and S1 protein. Besides these proteins, significant antibody responses to ORF9b and NSP5 are also identified. We show that the S1 specific IgG signal positively correlates with age and the level of lactate dehydrogenase (LDH) and negatively correlates with lymphocyte percentage. Overall, this study presents a systemic view of the SARS-CoV-2 specific IgG and IgM responses and provides insights to aid the development of effective diagnostic, therapeutic and vaccination strategies. url: https://www.ncbi.nlm.nih.gov/pubmed/32665645/ doi: 10.1038/s41467-020-17488-8 id: cord-298759-j965t808 author: Jiang, Nan title: Development of a robust Escherichia coli-based cell-free protein synthesis application platform date: 2020-10-17 words: 5253.0 sentences: 298.0 pages: flesch: 55.0 cache: ./cache/cord-298759-j965t808.txt txt: ./txt/cord-298759-j965t808.txt summary: The Escherichia coli-based system was chosen in this study, and the model protein deGFP was expressed to explore a more efficient cell-free system. To overcome these problems, cell-free protein synthesis (CFPS) has received new attention as an emerging synthetic biology technology, because it is an open system, not limited by cell growth or cell membrane, and it allows the use of various reaction formats. The selection of extracts, the size of the plasmid, the molecular crowding effect and the metal ion J o u r n a l P r e -p r o o f effect, which are important component parameters, were explored to improve the protein expression efficiency. Based on the optimized CFPS systems, the cell-free fundamental scientific research platform, primary screening platform, and portable biomolecular synthesis platform were established. Therefore, researchers need to optimize the metal ions and the corresponding concentration for the best cell-free protein synthesis. abstract: Since the cell-free protein synthesis system is not limited by the cell growth, all the substrates are used to produce the protein of interest, and the reaction environment can be flexibly controlled. All the advantages allow it to synthesize toxic proteins, membrane proteins, and unnatural proteins that are difficult to make in vivo. However, one typical reason why the cell-free system has not been widely accepted as a practical alternative, is its expression efficiency problem. The Escherichia coli-based system was chosen in this study, and the model protein deGFP was expressed to explore a more efficient cell-free system. The results showed that Mg2+ with a concentration of 15 mM in the cell-free system with BL21 Star (DE3) as the extract could better synthesize protein. The smaller the vectors, the lighter the burden, the higher the protein synthesis. Simulating the crowding effect in the cell does not improve the protein expression efficiency of the optimized cell-free protein synthesis system. Based on the optimized system, the cell-free fundamental research platform, primary screening platform, and portable biomolecular synthesis platform were established. This study provides a robust cell-free protein synthesis toolbox with easy extract preparation and high protein yield. It also enables more researchers to reap the benefits from the cell-free biosynthesis platform. url: https://api.elsevier.com/content/article/pii/S1369703X20303843 doi: 10.1016/j.bej.2020.107830 id: cord-001093-5l0fthw3 author: Jin, Fan title: Ligand Clouds around Protein Clouds: A Scenario of Ligand Binding with Intrinsically Disordered Proteins date: 2013-10-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Intrinsically disordered proteins (IDPs) were found to be widely associated with human diseases and may serve as potential drug design targets. However, drug design targeting IDPs is still in the very early stages. Progress in drug design is usually achieved using experimental screening; however, the structural disorder of IDPs makes it difficult to characterize their interaction with ligands using experiments alone. To better understand the structure of IDPs and their interactions with small molecule ligands, we performed extensive simulations on the c-Myc(370–409) peptide and its binding to a reported small molecule inhibitor, ligand 10074-A4. We found that the conformational space of the apo c-Myc(370–409) peptide was rather dispersed and that the conformations of the peptide were stabilized mainly by charge interactions and hydrogen bonds. Under the binding of the ligand, c-Myc(370–409) remained disordered. The ligand was found to bind to c-Myc(370–409) at different sites along the chain and behaved like a ‘ligand cloud’. In contrast to ligand binding to more rigid target proteins that usually results in a dominant bound structure, ligand binding to IDPs may better be described as ligand clouds around protein clouds. Nevertheless, the binding of the ligand and a non-ligand to the c-Myc(370–409) target could be clearly distinguished. The present study provides insights that will help improve rational drug design that targets IDPs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789766/ doi: 10.1371/journal.pcbi.1003249 id: cord-279586-likfvwwj author: Jin, Jian title: Effects of Sonication on the In vitro Digestibility and Structural Properties of Buckwheat Protein Isolates date: 2020-09-17 words: 4831.0 sentences: 248.0 pages: flesch: 48.0 cache: ./cache/cord-279586-likfvwwj.txt txt: ./txt/cord-279586-likfvwwj.txt summary: The present work investigated the effects of sonication at different amplitudes and durations on the in vitro digestibility of buckwheat protein isolates (BPIs). The tertiary structure analysis showed that sonication exposed the hydrophobic core buried inside the protein molecules and broke the intramolecular crosslinks, based on the increase in the surface hydrophobicity and intrinsic fluorescence and the decrease in the disulphide content. Therefore, this study was aimed at investigating the effects of sonication duration and acoustic amplitude on the in vitro digestibility of buckwheat protein isolates (BPIs). In addition, the effects of sonication on the tertiary structures (surface hydrophobicity, intrinsic fluorescence, sulfhydryl and disulfide bond contents), secondary structure, particle size, zeta-potential and microstructure of BPIs were studied to elucidate the structural mechanism underlying the effect of ultrasound on the digestibility of the proteins. abstract: The present work investigated the effects of sonication at different amplitudes and durations on the in vitro digestibility of buckwheat protein isolates (BPIs). The conformation, particle size and microstructures of the BPIs were also studied to explicate the possible mechanisms of the sonication-induced changes. The results showed that sonication conditions of 20 kHz, pulsed on-time 10 s, off-time 5s, amplitude of 60% and duration of 10 min (SA6T10) improved the digestibility of BPIs from 41.4% (control) to 58.2%. The tertiary structure analysis showed that sonication exposed the hydrophobic core buried inside the protein molecules and broke the intramolecular crosslinks, based on the increase in the surface hydrophobicity and intrinsic fluorescence and the decrease in the disulphide content. The secondary structure analysis showed that SA6T10 decreased the content of β-turn and β-sheet by 40.9% and 22.4%, respectively, and increased the content of anti-parallel β-sheet, random coil, and α-helix by 40.9%, 30.6%, and 25.5%, respectively. The particle size of the control BPIs (427.7±76.7 nm) increased to 2130.8±356.2 nm in the SA6T10 sonicated sample with a corresponding decrease in the polydispersity index from 0.97±0.04 to 0.51±0.13. Moreover, scanning electron microscopy indicated that sonication broke the macroparticles into smaller fragments and changed the surface state of the proteins. Taken together, sonication has proven to be a promising approach for improving the digestibility of buckwheat proteins, which can be explored as a source of plant-based alternative protein for food applications. url: https://doi.org/10.1016/j.ultsonch.2020.105348 doi: 10.1016/j.ultsonch.2020.105348 id: cord-301128-woe6knpv author: Joyeux, Marc title: Requirements for DNA-bridging proteins to act as topological barriers of the bacterial genome date: 2020-08-12 words: 4507.0 sentences: 226.0 pages: flesch: 51.0 cache: ./cache/cord-301128-woe6knpv.txt txt: ./txt/cord-301128-woe6knpv.txt summary: The results presented in this article reveal that the formation of DNA loops is by no means sufficient to create topologically independent domains and that DNA-bridging proteins must exert rather strong constraints on their binding sites in order to act as topological barriers: They must block the diffusion of the excess of twist through both binding sites and must additionally block the rotation of one DNA segment relative to the other one. We report below on our efforts to determine the minimal set of mandatory properties that allow molecular bridges to act as topological barriers and block the diffusion of torsional stress in out-of-equilibrium supercoiled chains. Since DNAbridging proteins form DNA loops by dynamically cross-linking widely separated DNA sites, the question amounts here to determine the constraints that must be imposed to beads α and β J o u r n a l P r e -p r o o f to divide the circular DNA chain into two topologically independent loops. abstract: Abstract Bacterial genomes have been shown to be partitioned into several kilobases long chromosomal domains that are topologically independent from each other, meaning that change of DNA superhelicity in one domain does not propagate to neighbors. Both in vivo and in vitro experiments have been performed to question the nature of the topological barriers at play, leading to several predictions on possible molecular actors. Here, we address the question of topological barriers using polymer models of supercoiled DNA chains that are constrained such as to mimic the action of predicted molecular actors. More specifically, we determine under which conditions DNA-bridging proteins may act as topological barriers. To this end, we developed a coarse-grained bead-and-spring model and investigated its properties through Brownian dynamics simulations. As a result, we find that DNA-bridging proteins must exert rather strong constraints on their binding sites: they must block the diffusion of the excess of twist through the two binding sites on the DNA molecule and, simultaneously, prevent the rotation of one DNA segment relative to the other one. Importantly, not all DNA-bridging proteins satisfy this second condition. For example, single bridges formed by proteins that bind DNA non-specifically, like H-NS dimers, are expected to fail with this respect. Our findings might also explain, in the case of specific DNA-bridging proteins like LacI, why multiple bridges are required to create stable independent topological domains. Strikingly, when the relative rotation of the DNA segments is not prevented, relaxation results in complex intrication of the two domains. Moreover, while the value of the torsional stress in each domain may vary, their differential is preserved. Our work also predicts that nucleoid associated proteins known to wrap DNA must form higher protein-DNA complexes to efficiently work as topological barriers. url: https://api.elsevier.com/content/article/pii/S0006349520306007 doi: 10.1016/j.bpj.2020.08.004 id: cord-295381-0dqu3p3y author: Kamal, Adeela title: Therapeutic and diagnostic implications of Hsp90 activation date: 2004-06-01 words: 5102.0 sentences: 211.0 pages: flesch: 37.0 cache: ./cache/cord-295381-0dqu3p3y.txt txt: ./txt/cord-295381-0dqu3p3y.txt summary: Recent work has identified the role of Hsp90 in multiple signal transduction pathways and revealed that the molecular mechanism of tumor selectivity by Hsp90 inhibitors is the result of an activated, high-affinity conformation of Hsp90 in tumors. A recent study reported that the Hsp90 in tumor cells is maintained in an activated conformation by the formation of multi-chaperone complexes that have increased ATPase activity and 100-fold greater binding affinity for 17-AAG compared with the uncomplexed, latent form of Hsp90 that is present in normal cells [28] . A model for Hsp90-dependent malignant progression has been proposed in which, as tumor cells gradually accumulate mutant and overexpressed signaling proteins, Hsp90 becomes engaged in the active chaperoning and stabilization of oncoproteins and adopts a high-affinity form that is induced by bound co-chaperone proteins ( Figure 3 ) [28] . FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinases abstract: Abstract The molecular chaperone heat-shock protein 90 (Hsp90) is involved in the stabilization and conformational maturation of many signaling proteins that are deregulated in cancers. Hsp90 inhibition results in the proteasomal degradation of these client proteins and leads to potent antitumor activity. The Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) is presently in clinical trials. Recent work has identified the role of Hsp90 in multiple signal transduction pathways and revealed that the molecular mechanism of tumor selectivity by Hsp90 inhibitors is the result of an activated, high-affinity conformation of Hsp90 in tumors. This review discusses these recent advances in the understanding of tumor Hsp90 for the treatment and diagnosis of cancer. In addition, the role of Hsp90 in non-oncological diseases will also be discussed. url: https://api.elsevier.com/content/article/pii/S1471491404001030 doi: 10.1016/j.molmed.2004.04.006 id: cord-338468-c0jv3i1t author: Kanduc, Darja title: From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry date: 2020-07-16 words: 4143.0 sentences: 234.0 pages: flesch: 41.0 cache: ./cache/cord-338468-c0jv3i1t.txt txt: ./txt/cord-338468-c0jv3i1t.txt summary: Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. In the wake of such results, in order to validate (or, as well, invalidate) the cross-reactivity hypothesis, investigation was expanded here by analyzing the peptide sharing between the human host and immunoreactive epitopes that are also present in SARS-CoV-2. Table 2 documents that numerous immunoreactive SARS-CoV-2 epitopes are composed mostly or, in many instances, uniquely of peptide sequences shared with human proteins. This study shows that hexapeptides from immunoreactive epitopes present in SARS-CoV-2 are widespread among a high number of human proteins. Table S2 : Hexapeptide sharing between 233 epitopes present in SARS-CoV-2 and human proteins. Table S3 : List and short description of 460 human proteins that share hexapeptides with the 233 SARS-CoV-2 epitopes. abstract: Aim: To define the autoimmune potential of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods: Experimentally validated epitopes cataloged at the Immune Epitope DataBase (IEDB) and present in SARS-CoV-2 were analyzed for peptide sharing with the human proteome. Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. Conclusions: This study represents a starting point or hint for future scientific–clinical investigations and suggests a range of possible protein targets of autoimmunity in SARS-CoV-2 infection. From an experimental perspective, the results warrant the testing of patients’ sera for autoantibodies against these protein targets. Clinically, the results warrant a stringent surveillance on the future pathologic sequelae of the current SARS-CoV-2 pandemic. url: https://doi.org/10.3390/antib9030033 doi: 10.3390/antib9030033 id: cord-322955-7dw32xby author: Kathwate, Gunderao H title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins date: 2020-06-12 words: 5729.0 sentences: 392.0 pages: flesch: 47.0 cache: ./cache/cord-322955-7dw32xby.txt txt: ./txt/cord-322955-7dw32xby.txt summary: title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Those properties are calculated by different methods at IEDB server (http://tools.iedb.org/bcell/ )like Kolaskar-Tongaonkar antigenicity scale provide physiology of the amino acid residues(45), Emini Surface accessible score for accessible surface of the epitope(46), Secondary structure of epitopes also has role in antigenicity. High scored and common peptides predicted by various tools were selected for deriving sequence of potential vaccine candidate. We designed a multi-epitopes vaccine construct from S-protein of SARS-CoV2. From various epitopes predicted by the online server based on common sequence and high score three TCR and two BCR epitopes were selected as part of COVID19 vaccine. This vaccine codes epitopes form S protein of SARS-CoV2 virus for T and B cell receptors. abstract: COVID 19 is disease caused by novel corona virus, SARS-CoV2 originated in China most probably of Bat origin. Till date, no specific vaccine or drug has been discovered to tackle the infections caused by SARS-CoV2. In response to this pandemic, we utilized bioinformatics knowledge to develop efficient vaccine candidate against SARS-CoV2. Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes were antigenic in nature non-toxic and probably non-allergen. Modelled and refined tertiary structure was predicted as valid for further use. Protein-Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. Designed multiepitope vaccine has induced cell mediated and humoral immunity along with increased interferon gamma response. Macrophages and dendritic cells were also found increased over the vaccine exposure. In silico codon optimization and cloning in expression vector indicates that vaccine can be efficiently expressed in E. coli. In conclusion, predicted vaccine is a good antigen, probable no allergen and has potential to induce cellular and humoral immunity. url: https://doi.org/10.1101/2020.06.03.131755 doi: 10.1101/2020.06.03.131755 id: cord-272268-8vrcwwll author: Kedersha, Nancy title: Chapter 4 Regulation of Translation by Stress Granules and Processing Bodies date: 2009-10-27 words: 8598.0 sentences: 456.0 pages: flesch: 45.0 cache: ./cache/cord-272268-8vrcwwll.txt txt: ./txt/cord-272268-8vrcwwll.txt summary: Cytoplasmic stress granules (SGs) and processing bodies (PBs) are dynamic structures that form in response to stress-induced translational arrest. Critical components of the ''''cell biology'''' of protein translation are mRNP granules known as processing bodies (PBs) and stress granules (SGs). These transient cytoplasmic ''''structures'''' are actively assembled from untranslated mRNA by a host of RNA-binding proteins, which determine whether specific transcripts will be reinitiated, degraded, or stored. In 1999, it was noted that stress-induced translational arrest causes untranslated mRNPs to assemble into large cytoplasmic ''''SGs,'''' whose formation is triggered by, and dependent upon, the phosphorylation of eIF2a. Virus infection also induces the assembly of SGs and PBs suggesting that RNA granules play a role in reprogramming mRNA translation/decay during viral infection. RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2a to the assembly of mammalian stress granules abstract: Stress necessitates rapid reprogramming of translation in order to facilitate an adaptive response and promote survival. Cytoplasmic stress granules (SGs) and processing bodies (PBs) are dynamic structures that form in response to stress-induced translational arrest. PBs are linked to mRNA silencing and decay, while SGs are more closely linked to translation and the sorting of specific mRNAs for different fates. While they share some components and can interact physically, SGs and PBs are regulated independently, house separate functions, and contain unique markers. SG formation is associated with numerous disease states, and the expanding list of SG-associated proteins integrates SG formation with other processes such as transcription, splicing, and survival. Growing evidence suggests that SG assembly is initiated by translational arrest, and mediates cross talk with many other signaling pathways. url: https://api.elsevier.com/content/article/pii/S1877117309900047 doi: 10.1016/s1877-1173(09)90004-7 id: cord-291727-4wfhuvww author: Ketteler, Robin title: On programmed ribosomal frameshifting: the alternative proteomes date: 2012-11-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Frameshifting results from two main mechanisms: genomic insertions or deletions (indels) or programmed ribosomal frameshifting. Whereas indels can disrupt normal protein function, programmed ribosomal frameshifting can result in dual-coding genes, each of which can produce multiple functional products. Here, I summarize technical advances that have made it possible to identify programmed ribosomal frameshifting events in a systematic way. The results of these studies suggest that such frameshifting occurs in all genomes, and I will discuss methods that could help characterize the resulting alternative proteomes. url: https://www.ncbi.nlm.nih.gov/pubmed/23181069/ doi: 10.3389/fgene.2012.00242 id: cord-346819-11fkgzaa author: Khan, Mohd Imran title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date: 2020-09-03 words: 4405.0 sentences: 291.0 pages: flesch: 57.0 cache: ./cache/cord-346819-11fkgzaa.txt txt: ./txt/cord-346819-11fkgzaa.txt summary: title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. The genome analysis of the SARS-CoV-2 strains from 13 different countries showed a large number of mutations within the major structural proteins. This study provides a deeper insight into the emergence of these mutations within the major structural as well as nsp encoded by the SARS-CoV-2 genome from different countries. Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations backbone RMSD was also noticed (Fig 4A) . abstract: A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. In this study, we have made an attempt to investigate the SARS-CoV-2 genome reported from 13 different countries, identification of mutations in major coronavirus proteins of these different SARS-CoV-2 genomes and compared with SARS-CoV. These thirteen complete genome sequences of SARS-CoV-2 showed high identity (>99%) to each other, while they shared 82% identity with SARS-CoV. Here, we performed a very systematic mutational analysis of SARS-CoV-2 genomes from different geographical locations, which enabled us to identify numerous unique features of this viral genome. This includes several important country-specific unique mutations in the major proteins of SARS-CoV-2 namely, replicase polyprotein, spike glycoprotein, envelope protein and nucleocapsid protein. Indian strain showed mutation in spike glycoprotein at R408I and in replicase polyprotein at I671T, P2144S and A2798V,. While the spike protein of Spain & South Korea carried F797C and S221W mutation, respectively. Likewise, several important country specific mutations were analyzed. The effect of mutations of these major proteins were also investigated using various in silico approaches. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. It was found that the R60C mutation in Mpro affects the protein dynamics, thereby, affecting the binding of inhibitor within its active site. The implications of mutation on structural characteristics were determined. The information provided in this manuscript holds great potential in further scientific research towards the design of potential vaccine candidates/small molecular inhibitor against COVID19. url: https://www.ncbi.nlm.nih.gov/pubmed/32881907/ doi: 10.1371/journal.pone.0238344 id: cord-304343-m7tbdfri author: Khandia, Rekha title: A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy date: 2019-07-03 words: 20281.0 sentences: 1088.0 pages: flesch: 32.0 cache: ./cache/cord-304343-m7tbdfri.txt txt: ./txt/cord-304343-m7tbdfri.txt summary: Similarly, inhibiting the mTOR signaling pathway can prevent apoptosis and even enhance necroptosis, whereas starvation, which induces autophagy, protects cells from zVAD-mediated necroptotic death [194] . For instance, autophagy has been demonstrated to be actively involved in the replication of influenza A virus (IAV), which induces autophagosome formation during the early phase of infection and later inhibits autophagosomal maturation by preventing autophagosomal-lysosomal fusion and promoting autophagosomes to accumulate in virus-infected cells [253] . (5) A novel anti-cancer molecule, HA15, which targets HSPA5/BIP was shown to induce endoplasmic reticulum stress and increase the unfolded protein response, resulting in cancer cell death through autophagy and apoptosis. (5) A novel anti-cancer molecule, HA15, which targets HSPA5/BIP was shown to induce endoplasmic reticulum stress and increase the unfolded protein response, resulting in cancer cell death through autophagy and apoptosis. In addition, the novel anti-cancer molecule HA15, which targets HSPA5/BIP, was shown to induce ER stress and increase the unfolded protein response, resulting in cancer cell death via autophagy and apoptosis [304] . abstract: Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health. url: https://doi.org/10.3390/cells8070674 doi: 10.3390/cells8070674 id: cord-341129-eo0vjcmk author: Kielian, Margaret title: Virus membrane-fusion proteins: more than one way to make a hairpin date: 2006 words: 6986.0 sentences: 333.0 pages: flesch: 45.0 cache: ./cache/cord-341129-eo0vjcmk.txt txt: ./txt/cord-341129-eo0vjcmk.txt summary: Virus membrane-fusion proteins drive the fusion reaction by undergoing a major conformational change that is triggered by interactions with the target cell. The class I membrane-fusion reaction is mediated by the refolding of the fusion protein to a highly stable rod-like structure with a central trimeric α-helical coiled coil. In vitro studies using the ectodomains of both the alphavirus and flavivirus proteins showed that trimerization requires insertion of the fusion peptide into target membranes 64, 65 . However, H230A virus undergoes apparently normal conformational changes upon exposure to low pH, including heterodimer dissociation and fusion-loop exposure, cholesterol-dependent target-membrane insertion, and formation of the E1 homotrimer. Recent work indicates that exogenous domain III blocks class II membrane fusion and infection by binding to the fusion protein during the low-pH-induced conformational change 92 . abstract: Structure–function studies have defined two classes of viral membrane-fusion proteins that have radically different architectures but adopt a similar overall 'hairpin' conformation to induce fusion of the viral and cellular membranes and therefore initiate infection. In both classes, the hairpin conformation is achieved after a conformational change is triggered by interaction with the target cell. This review will focus in particular on the properties of the more recently described class II proteins. url: https://www.ncbi.nlm.nih.gov/pubmed/16357862/ doi: 10.1038/nrmicro1326 id: cord-254957-jqp1gto6 author: Klann, Kevin title: Growth factor receptor signaling inhibition prevents SARS-CoV-2 replication date: 2020-08-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Summary SARS-CoV-2 infections are rapidly spreading around the globe. The rapid development of therapies is of major importance. However, our lack of understanding of the molecular processes and host cell signaling events underlying SARS-CoV-2 infection hinder therapy development. We employed a SARS-CoV-2 infection system in permissible human cells to study signaling changes by phospho-proteomics. We identified viral protein phosphorylation and defined phosphorylation-driven host cell signaling changes upon infection. Growth factor receptor (GFR) signaling and downstream pathways were activated. Drug-protein network analyses revealed GFR signaling as key pathway targetable by approved drugs. Inhibition of GFR downstream signaling by five compounds prevented SARS-CoV-2 replication in cells, assessed by cytopathic effect, viral dsRNA production, and viral RNA release into the supernatant. This study describes host cell signaling events upon SARS-CoV-2 infection and reveals GFR signaling as central pathway essential for SARS-CoV-2 replication. It provides with novel strategies for COVID-19 treatment. url: https://www.ncbi.nlm.nih.gov/pubmed/32877642/ doi: 10.1016/j.molcel.2020.08.006 id: cord-266543-ng9zr299 author: Klebe, Gerhard title: Virtual ligand screening: strategies, perspectives and limitations date: 2006-06-20 words: 11098.0 sentences: 527.0 pages: flesch: 41.0 cache: ./cache/cord-266543-ng9zr299.txt txt: ./txt/cord-266543-ng9zr299.txt summary: In consequence, either the three-dimensional (3D) structure of the macromolecular target -as given by crystal structure analyses, NMR or sophisticated homology modelling -or, at the very least, a rigid reference ligand with a known bioactive conformation mapping out the putative receptor binding site must be available [5] . If one excludes purely retrospective studies, in which the potential of a method is demonstrated by its ability to enrich putatively active molecules from a sample of anticipated nonactive ones, 50 targets have been studied to date, and reports on the discovery of mostly micromolar binding ligands in a truly predictive fashion are available (Table 1) . With respect to VS, a unique and precise assignment of the protonation states of the ligand and protein functional groups in a pK a range between 3 and 11 is essential because, for example, for docking it is important whether such a group is considered as donor or acceptor of a hydrogen bond (Krämer and Klebe, unpublished). abstract: In contrast to high-throughput screening, in virtual ligand screening (VS), compounds are selected using computer programs to predict their binding to a target receptor. A key prerequisite is knowledge about the spatial and energetic criteria responsible for protein–ligand binding. The concepts and prerequisites to perform VS are summarized here, and explanations are sought for the enduring limitations of the technology. Target selection, analysis and preparation are discussed, as well as considerations about the compilation of candidate ligand libraries. The tools and strategies of a VS campaign, and the accuracy of scoring and ranking of the results, are also considered. url: https://www.sciencedirect.com/science/article/pii/S1359644606001784 doi: 10.1016/j.drudis.2006.05.012 id: cord-007755-o2r8ktie author: Kokoszka, Malgorzata E. title: Mapping Protein–Protein Interactions with Phage-Displayed Combinatorial Peptide Libraries and Alanine Scanning date: 2014-10-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: One avenue for inferring the function of a protein is to learn what proteins it may bind to in the cell. Among the various methodologies, one way for doing so is to affinity select peptide ligands from a phage-displayed combinatorial peptide library and then to examine if the proteins that carry such peptide sequences interact with the target protein in the cell. With the protocols described in this chapter, a laboratory with skills in microbiology, molecular biology, and protein biochemistry can readily identify peptides in the library that bind selectively, and with micromolar affinity, to a given target protein on the time scale of 2 months. To illustrate this approach, we use a library of bacteriophage M13 particles, which display 12-mer combinatorial peptides, to affinity select different peptide ligands for two different targets, the SH3 domain of the human Lyn protein tyrosine kinase and a segment of the yeast serine/threonine protein kinase Cbk1. The binding properties of the selected peptide ligands are then dissected by sequence alignment, Kunkel mutagenesis, and alanine scanning. Finally, the peptide ligands can be used to predict cellular interacting proteins and serve as the starting point for drug discovery. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122165/ doi: 10.1007/978-1-4939-2020-4_12 id: cord-258363-gmgbus9i author: Kolla, Venkatadri title: Synthesis of a bacteriophage MB78 late protein by novel ribosomal frameshifting() date: 2000-08-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: MB78 is a virulent phage of Salmonella typhimurium that possesses a number of interesting features, making it a suitable organism to study the regulation of gene expression. A detailed physical map of this phage genome has been constructed and is being extensively studied at the molecular level. Here, we demonstrate the expression of two late proteins of bacteriophage MB78 derived from the same gene as a result of possible ribosomal frameshifting. In vitro transcription-translation yields a major protein that migrates as 28 kDa, whereas in vivo expression using pET expression vectors yields two equally expressed proteins of molecular sizes 28 and 26 kDa. A putative slippery sequence TTTAAAG and a pseudoknot structure, two essential cis elements required for the classical ribosomal frameshifting, are identified in the reading frame. Mutations created at the slippery sequence resulted in a single 28 kDa protein and completely abolished the expression of 26 kDa protein. Thus, we have produced the first evidence that ribosomal frameshifting occurs in bacteriophage MB78 of Salmonella typhimurium. url: https://www.sciencedirect.com/science/article/pii/S037811190000264X doi: 10.1016/s0378-1119(00)00264-x id: cord-309384-vlk8cebh author: Kolter, Thomas title: Ganglioside Biochemistry date: 2012-12-19 words: 16840.0 sentences: 960.0 pages: flesch: 38.0 cache: ./cache/cord-309384-vlk8cebh.txt txt: ./txt/cord-309384-vlk8cebh.txt summary: A principal difference between ganglioside biosynthesis in the Golgi apparatus and degradation in the endolysosomal compartment is that during GSL formation, membranebound glycosyltransferases interact with their membranebound glycolipid substrates by diffusion within the twodimensional plane of the lipid bilayer. As glycosidase substrates, GSLs with four carbohydrate residues or less require the additional presence of small lipid binding glycoproteins, either the GM2 activator protein or one of the four saposins A-D. In vitro, in addition to enzymes and activator proteins, also an appropriate membrane-lipid composition of the ganglioside-containing membrane is required for degradation [222] . Due to the deficiency of two enzyme activities, β-hexosaminidases A and B, storage of negatively charged glycolipids characteristic for Tay-Sachs disease and, in addition, of uncharged substrates such as GA2 in the brain and globoside in visceral organs (Figure 16 ) is observed. abstract: Gangliosides are sialic acid-containing glycosphingolipids. They occur especially on the cellular surfaces of neuronal cells, where they form a complex pattern, but are also found in many other cell types. The paper provides a general overview on their structures, occurrence, and metabolism. Key functional, biochemical, and pathobiochemical aspects are summarized. url: https://www.ncbi.nlm.nih.gov/pubmed/25969757/ doi: 10.5402/2012/506160 id: cord-259505-7hiss0j3 author: Kong, Qingming title: Proteomic analysis of purified coronavirus infectious bronchitis virus particles date: 2010-06-09 words: 6907.0 sentences: 355.0 pages: flesch: 44.0 cache: ./cache/cord-259505-7hiss0j3.txt txt: ./txt/cord-259505-7hiss0j3.txt summary: It is an important prerequisite for the functional studies to know the protein composition of the purified viral particles, as it allows the analysis of specific proteins and their roles during the virus life cycle, resulting in better understanding of the infection process and the pathogenesis of viruses. To date, there have been no reports about TENP associated with virus, but it''s an enriched and abundant protein identified in purified infectious bronchitis particles which suggests to us that it may be a requisite host protein in IBV life cycles. The present study 1) provides the first proteomic analysis of infectious bronchitis particles, 2) establishes the most comprehensive proteomic index of IBV and 3) shows that most of the virion incorporated host proteins have central roles in virus life cycle. abstract: BACKGROUND: Infectious bronchitis virus (IBV) is the coronavirus of domestic chickens causing major economic losses to the poultry industry. Because of the complexity of the IBV life cycle and the small number of viral structural proteins, important virus-host relationships likely remain to be discovered. Toward this goal, we performed two-dimensional gel electrophoresis fractionation coupled to mass spectrometry identification approaches to perform a comprehensive proteomic analysis of purified IBV particles. RESULTS: Apart from the virus-encoded structural proteins, we detected 60 host proteins in the purified virions which can be grouped into several functional categories including intracellular trafficking proteins (20%), molecular chaperone (18%), macromolcular biosynthesis proteins (17%), cytoskeletal proteins (15%), signal transport proteins (15%), protein degradation (8%), chromosome associated proteins (2%), ribosomal proteins (2%), and other function proteins (3%). Interestingly, 21 of the total host proteins have not been reported to be present in virions of other virus families, such as major vault protein, TENP protein, ovalbumin, and scavenger receptor protein. Following identification of the host proteins by proteomic methods, the presence of 4 proteins in the purified IBV preparation was verified by western blotting and immunogold labeling detection. CONCLUSIONS: The results present the first standard proteomic profile of IBV and may facilitate the understanding of the pathogenic mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/20534109/ doi: 10.1186/1477-5956-8-29 id: cord-017400-jxbhdch8 author: Koroleva, Olga title: Proteomic Analysis of the Plant Nucleolus date: 2007 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The nucleolus is a prominent sub-nuclear structure found in all eukaryotes. It is where the ribosomal RNA genes are transcribed and ribosomes are synthesised. However, much evidence has now accumulated that the nucleolus is involved in many other nuclear processes. Nucleoli are of moderate protein complexity, comprising a few hundred proteins, and can be isolated for proteomic analysis. In this chapter we describe the purification and analysis of plant nucleoli by proteomic methods and summarise the current results. We also discuss more specific tagging methods that have been used to analyse individual protein complexes, as well as methods for analysing post-translational modifications of nucleolar proteins. Finally we discuss the assessment of the reliability of such proteomic data, and the presentation and curation of this type of data. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121954/ doi: 10.1007/978-3-540-72617-3_16 id: cord-008556-oetrdm8g author: Kozak, Marilyn title: Regulation of Protein Synthesis in Virus-Infected Animal Cells date: 2008-03-01 words: 23945.0 sentences: 1270.0 pages: flesch: 51.0 cache: ./cache/cord-008556-oetrdm8g.txt txt: ./txt/cord-008556-oetrdm8g.txt summary: One consequence of the scanning mechanism is that deleting the "ribosome binding site" (i.e., the normal initiator codon and flanking sequences) will not abolish translation; ribosomes will simply use the next AUG codon downstream, which, in some cases, has been shown to direct the synthesis of a biologically active, truncated protein (Downey et al., 1984; Halpern and Smiley, 1984; Katinka and Yaniv, 1982) . The best evidence for this is the ability of both EMC and SFV 26 S mRNA to be translated in EMC virus-infected cells, in which host translation is drastically inhibited by a mechanism that has not been difined, but that clearly does not involve cap binding protein (Mosenkis et al., 1985) . In wild-type adenovirus-infected cells, in which host protein synthesis is drastically reduced, both adenovirus and influenza virus mRNAs are translated efficiently. abstract: This chapter summarizes the structural features that govern the translation of viral mRNAs: where the synthesis of a protein starts and ends, how many proteins can be produced from one mRNA, and how efficiently. It focuses on the interplay between viral and cellular mRNAs and the translational machinery. That interplay, together with the intrinsic structure of viral mRNAs, determines the patterns of translation in infected cells. It also points out some possibilities for translational regulation that can only be glimpsed at present, but are likely to come into focus in the future. The mechanism of selecting the initiation site for protein synthesis appears to follow a single formula. The translational machinery displays a certain flexibility that is exploited more frequently by viral than by cellular mRNAs. Although some of the parameters that determine efficiency have been identified, how efficiently a given mRNA will be translated cannot be predicted by summing the known parameters. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131717/ doi: 10.1016/s0065-3527(08)60265-1 id: cord-267475-6f4h3cck author: Kozak, Marilyn title: Pushing the limits of the scanning mechanism for initiation of translation date: 2002-10-16 words: 24538.0 sentences: 1234.0 pages: flesch: 50.0 cache: ./cache/cord-267475-6f4h3cck.txt txt: ./txt/cord-267475-6f4h3cck.txt summary: This depends on careful structural arrangements, however, which are rarely present in cellular mRNAs. Understanding the rules for initiation of translation enables understanding of human diseases in which the expression of a critical gene is reduced by mutations that add upstream AUG codons or change the context around the AUG(START) codon. (Whether the second AUG codon resides in a strong or weak context is not relevant; the ribosome reads the mRNA linearly and thus the decision to stop or to bypass the first AUG is not influenced by whether there is a better initiation site downstream.) The large number of genes that employ leaky scanning precludes discussion of the biological significance of the proteins thereby produced, but it merits noting that, for many of the viruses in Table 3 , replication requires production of both listed proteins. abstract: Selection of the translational initiation site in most eukaryotic mRNAs appears to occur via a scanning mechanism which predicts that proximity to the 5′ end plays a dominant role in identifying the start codon. This ‘position effect’ is seen in cases where a mutation creates an AUG codon upstream from the normal start site and translation shifts to the upstream site. The position effect is evident also in cases where a silent internal AUG codon is activated upon being relocated closer to the 5′ end. Two mechanisms for escaping the first-AUG rule – reinitiation and context-dependent leaky scanning – enable downstream AUG codons to be accessed in some mRNAs. Although these mechanisms are not new, many new examples of their use have emerged. Via these escape pathways, the scanning mechanism operates even in extreme cases, such as a plant virus mRNA in which translation initiates from three start sites over a distance of 900 nt. This depends on careful structural arrangements, however, which are rarely present in cellular mRNAs. Understanding the rules for initiation of translation enables understanding of human diseases in which the expression of a critical gene is reduced by mutations that add upstream AUG codons or change the context around the AUG(START) codon. The opposite problem occurs in the case of hereditary thrombocythemia: translational efficiency is increased by mutations that remove or restructure a small upstream open reading frame in thrombopoietin mRNA, and the resulting overproduction of the cytokine causes the disease. This and other examples support the idea that 5′ leader sequences are sometimes structured deliberately in a way that constrains scanning in order to prevent harmful overproduction of potent regulatory proteins. The accumulated evidence reveals how the scanning mechanism dictates the pattern of transcription – forcing production of monocistronic mRNAs – and the pattern of translation of eukaryotic cellular and viral genes. url: https://api.elsevier.com/content/article/pii/S0378111902010569 doi: 10.1016/s0378-1119(02)01056-9 id: cord-272241-2fwz8z8n author: Kumar, Amit title: Exploring the SARS-CoV-2 structural proteins for multi-epitope vaccine development: an in-silico approach date: 2020-09-09 words: 4608.0 sentences: 281.0 pages: flesch: 49.0 cache: ./cache/cord-272241-2fwz8z8n.txt txt: ./txt/cord-272241-2fwz8z8n.txt summary: title: Exploring the SARS-CoV-2 structural proteins for multi-epitope vaccine development: an in-silico approach Hence, in this study, we have used immunoinformatic approaches to predict highly antigenic epitopes from SARS-CoV-2 structural proteins that would evoke a strong immune response in humans. For this purpose, we have used the structural proteins: Spike, Envelope, and nucleocapsid to predict B-cell, cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes for construction of vaccine. We have also performed the docking and molecular dynamic simulations (MDS) between the vaccine and human Toll-like Receptor-3 (TLR-3) to study their binding stability. The VaxiJen 2.0 server predicts the antigenicity of the multi-epitope vaccine peptide based on the physicochemical properties of the input protein. Whereas, ANTIGENpro server predicts the antigenicity of the multi-epitopic vaccine based on the protein microarray data analysis of the target organism. Three structural proteins (spike glycoprotein, nucleocapsid, and envelope) were selected to construct a multi-epitope vaccine, which is capable of eliciting the humoral and cell-mediated immune response. abstract: INTRODUCTION: The ongoing life-threatening pandemic of coronavirus disease 2019 (COVID-19) has extensively affected the world. During this global health crisis, it is fundamentally crucial to find strategies to combat SARS-CoV-2. Despite several efforts in this direction and continuing clinical trials, no vaccine has been approved for it yet. METHODS: To find a preventive measure, we have computationally designed a multi-epitopic subunit vaccine using immuno-informatic approaches. RESULTS: The structural proteins of SARS-CoV-2 involved in its survival and pathogenicity were used to predict antigenic epitopes. The antigenic epitopes were capable of eliciting a strong humoral as well as cell-mediated immune response, our predictions suggest. The final vaccine was constructed by joining the all epitopes with specific linkers and to enhance their stability and immunogenicity. The physicochemical property of the vaccine was assessed. The vaccine 3D structure prediction and validation were done and docked with the human TLR-3 receptor. Furthermore, molecular dynamics simulations of the vaccine-TLR-3 receptor complex are employed to assess its dynamic motions and binding stability in-silico. CONCLUSION: Based on this study, we strongly suggest synthesizing this vaccine, which further can be tested in-vitro and in-vivo to check its potency in a cure for COVID-19. url: https://doi.org/10.1080/14760584.2020.1813576 doi: 10.1080/14760584.2020.1813576 id: cord-269531-7gy4epzo author: Kumar, Pankaj title: Proteomic analysis of purified turkey adenovirus 3 virions date: 2015-07-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Turkey adenovirus 3 (TAdV-3) causes high mortality and significant economic losses to the turkey industry. However, little is known about the molecular determinants required for viral replication and pathogenesis. Moreover, TAdV-3 does not grow well in cell culture, thus detailed structural studies of the infectious particle is particularly challenging. To develop a better understanding of virus-host interactions, we performed a comprehensive proteomic analysis of proteinase K treated purified TAdV-3 virions isolated from spleens of infected turkeys, by utilizing one-dimensional liquid chromatography mass spectrometry. Our analysis resulted in the identification of 13 viral proteins associated with TAdV-3 virions including a novel uncharacterized TaV3gp04 protein. Further, we detected 18 host proteins in purified virions, many of which are involved in cell-to cell spread, cytoskeleton dynamics and virus replication. Notably, seven of these host proteins have not yet been reported to be present in any other purified virus. In addition, five of these proteins are known antiviral host restriction factors. The availability of reagents allowed us to identify two cellular proteins (collagen alpha-1 (VI) chain and haemoglobin) in the purified TAdV-3 preparations. These results represent the first comprehensive proteomic profile of TAdV-3 and may provide information for illustrating TAdV-3 replication and pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0214-z) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1186/s13567-015-0214-z doi: 10.1186/s13567-015-0214-z id: cord-352371-t54zftal author: Kumar, Ravindra title: Prediction of endoplasmic reticulum resident proteins using fragmented amino acid composition and support vector machine date: 2017-09-04 words: 6606.0 sentences: 343.0 pages: flesch: 54.0 cache: ./cache/cord-352371-t54zftal.txt txt: ./txt/cord-352371-t54zftal.txt summary: RESULTS: In this study, we have reported a novel support vector machine based method for predicting endoplasmic reticulum resident proteins, named as ERPred. But these have some shortcomings like (i) among the above mentioned predictors, none were designed specifically to predict ERRPs; (ii) datasets used for training for prediction model were very old; (iii) subcellular locations were determined for a particular organism or groups (plant/animal/viral); (iv) many of them do not provide webserver/standalone software for scientific purpose and if some of them does so, they are not in working condition. Using standalone version of ScanProsite (Gattiker, Gasteiger & Bairoch, 2002) , out of 124 proteins of training dataset, we were able to find ER retention signal ([KRHQSA]-[DENQ]-E-L) in only 66 proteins, which shows that signal sequence is not present in all ERRPs. This shows that signal based approach may not be appropriate for complete ERRP repertoire prediction of any proteome. abstract: BACKGROUND: The endoplasmic reticulum plays an important role in many cellular processes, which includes protein synthesis, folding and post-translational processing of newly synthesized proteins. It is also the site for quality control of misfolded proteins and entry point of extracellular proteins to the secretory pathway. Hence at any given point of time, endoplasmic reticulum contains two different cohorts of proteins, (i) proteins involved in endoplasmic reticulum-specific function, which reside in the lumen of the endoplasmic reticulum, called as endoplasmic reticulum resident proteins and (ii) proteins which are in process of moving to the extracellular space. Thus, endoplasmic reticulum resident proteins must somehow be distinguished from newly synthesized secretory proteins, which pass through the endoplasmic reticulum on their way out of the cell. Approximately only 50% of the proteins used in this study as training data had endoplasmic reticulum retention signal, which shows that these signals are not essentially present in all endoplasmic reticulum resident proteins. This also strongly indicates the role of additional factors in retention of endoplasmic reticulum-specific proteins inside the endoplasmic reticulum. METHODS: This is a support vector machine based method, where we had used different forms of protein features as inputs for support vector machine to develop the prediction models. During training leave-one-out approach of cross-validation was used. Maximum performance was obtained with a combination of amino acid compositions of different part of proteins. RESULTS: In this study, we have reported a novel support vector machine based method for predicting endoplasmic reticulum resident proteins, named as ERPred. During training we achieved a maximum accuracy of 81.42% with leave-one-out approach of cross-validation. When evaluated on independent dataset, ERPred did prediction with sensitivity of 72.31% and specificity of 83.69%. We have also annotated six different proteomes to predict the candidate endoplasmic reticulum resident proteins in them. A webserver, ERPred, was developed to make the method available to the scientific community, which can be accessed at http://proteininformatics.org/mkumar/erpred/index.html. DISCUSSION: We found that out of 124 proteins of the training dataset, only 66 proteins had endoplasmic reticulum retention signals, which shows that these signals are not an absolute necessity for endoplasmic reticulum resident proteins to remain inside the endoplasmic reticulum. This observation also strongly indicates the role of additional factors in retention of proteins inside the endoplasmic reticulum. Our proposed predictor, ERPred, is a signal independent tool. It is tuned for the prediction of endoplasmic reticulum resident proteins, even if the query protein does not contain specific ER-retention signal. url: https://doi.org/10.7717/peerj.3561 doi: 10.7717/peerj.3561 id: cord-329448-kxxy60x9 author: Kumari, Sudha title: Endocytosis unplugged: multiple ways to enter the cell date: 2010-02-02 words: 11521.0 sentences: 541.0 pages: flesch: 31.0 cache: ./cache/cord-329448-kxxy60x9.txt txt: ./txt/cord-329448-kxxy60x9.txt summary: These factors include one or more underlying principle in cargo enrichment, necessitating specific coat and coat-associated protein assembly, a scission mechanism, and a means to integrate these steps; several molecules and membrane parameters can influence and diversify an endocytic process. CtBP1/BARS (C-terminal-binding protein-1/brefeldin A ribosylation substrate) proteins were originally demonstrated to regulate dynamin-independent fluid uptake in a variety of cell lines, and were later reported to localize to the site of and affect macropinosome membrane closure in a phosphorylation-dependent manner [36] . Overexpression of dominant negative, GTP-binding mutants of dynamin also blocked receptor-mediated endocytosis in various cells, suggesting a role for the GTPase activity of dynamin in the clathrin-dependent endocytic process outside the nervous system. The identification of an endocytic pathway as distinct has been primarily based on associated cargo proteins or lipids, and molecular regulators; the contribution of kinetics and detailed physical mechanism to such categorization is not generally available except in some wellcharacterized situations, namely clathrin-pit endocytosis or endocytosis by actin-dependent forces in yeast. abstract: Endocytosis occurs at the cell surface and involves internalization of the plasma membrane (PM) along with its constituent membrane proteins and lipids. Endocytosis is involved in sampling of the extracellular milieu and also serves to regulate various processes initiated at the cell surface. These include nutrient uptake, signaling from cell-surface receptors, and many other processes essential for cell and tissue functioning in metazoans. It is also central to the maintenance of PM lipid and protein homeostasis. There are multiple means of internalization that operate concurrently, at the cell surface. With advancement in high-resolution visualization techniques, it is now possible to track multiple endocytic cargo at the same time, revealing a remarkable diversity of endocytic processes in a single cell. A combination of live cell imaging and efficient genetic manipulations has also aided in understanding the functional hierarchy of molecular players in these mechanisms of internalization. Here we provide an account of various endocytic routes, their mechanisms of operation and occurrence across phyla. url: https://www.ncbi.nlm.nih.gov/pubmed/20125123/ doi: 10.1038/cr.2010.19 id: cord-323768-r7jbm1et author: Lagarda-Diaz, Irlanda title: Legume Lectins: Proteins with Diverse Applications date: 2017-06-12 words: 6811.0 sentences: 368.0 pages: flesch: 41.0 cache: ./cache/cord-323768-r7jbm1et.txt txt: ./txt/cord-323768-r7jbm1et.txt summary: Because lectins recognize and bind to specific glycoconjugates present on the surface of cells and intracellular structures; they can serve as potential target molecules for developing practical applications in the fields of food; agriculture; health and pharmaceutical research. This review presents the current knowledge of the main structural characteristics of legume lectins and the relationship of structure to the exhibited specificities; provides an overview of their particular antimicrobial; insecticidal and antitumor biological activities and describes possible applications based on the pattern of recognized glyco-targets. The isolation and purification of lectins from seeds of native plants such as Parkinsonia aculeata, Olneya tesota, Acacia constricta, Prosopis juliflora, Cercidium praecox, Caesalpinia caladenia and Phaseolus acutifolius has been described. Purification and characterization of complex carbohydrate specific isolectins from wild legume seeds: Acacia constricta is (vinorama) highly homologous to Phaseolus Vulgaris lectins abstract: Lectins are a diverse class of proteins distributed extensively in nature. Among these proteins; legume lectins display a variety of interesting features including antimicrobial; insecticidal and antitumor activities. Because lectins recognize and bind to specific glycoconjugates present on the surface of cells and intracellular structures; they can serve as potential target molecules for developing practical applications in the fields of food; agriculture; health and pharmaceutical research. This review presents the current knowledge of the main structural characteristics of legume lectins and the relationship of structure to the exhibited specificities; provides an overview of their particular antimicrobial; insecticidal and antitumor biological activities and describes possible applications based on the pattern of recognized glyco-targets. url: https://www.ncbi.nlm.nih.gov/pubmed/28604616/ doi: 10.3390/ijms18061242 id: cord-264392-he1vekrt author: Lambeth, L. S. title: Complete genome sequence of Nariva virus, a rodent paramyxovirus date: 2008-12-23 words: 4363.0 sentences: 204.0 pages: flesch: 52.0 cache: ./cache/cord-264392-he1vekrt.txt txt: ./txt/cord-264392-he1vekrt.txt summary: This study confirmed the classification of NarPV as a member of the subfamily Paramyxovirinae and established the close genome organization and sequence relationship between the two rodent paramyxoviruses isolated almost a decade apart and from two locations separated by more than 15,000 km. This was then followed by PCR to fill in the ''''gaps'''' using specific primers designed from NarPV Nariva virus genome 201 sequences obtained from the cDNA subtraction or degenerate primers designed using highly conserved consensus sequences of known paramyxoviruses in the subfamily Paramyxovirinae. Overall comparison of deduced sizes and amino acid sequences of all proteins indicated that NarPV is most closely related to MosPV (Table 1) genome is significantly larger (16,650 nt) than that of NarPV due to the longer untranslated regions (UTRs) located at the 3 0 end of most genes ( Fig. 1b and Table 1 ). abstract: Nariva virus (NarPV) was isolated from forest rodents (Zygodontomys b. brevicauda) in eastern Trinidad in the early 1960s. Initial classification within the family Paramyxoviridae was based mainly on morphological observations including the structure of nucleocapsids and virion surface projections. Here, we report the characterization of the complete genome sequence of NarPV. The genome is 15,276 nucleotides in length, conforming to the rule-of-six, and has a genome organization typical of most members of the family, with six transcriptional units in the order 3′-N–P-M-F–H-L-5′. The gene junctions contain highly conserved gene start and stop signals and a tri-nucleotide intergenic sequence present in most members of the subfamily Paramyxovirinae. Sequence comparison studies indicate that NarPV is most closely related to Mossman virus, which was isolated from wild rats (Rattus leucopus) in Queensland, Australia, in 1970. This study confirmed the classification of NarPV as a member of the subfamily Paramyxovirinae and established the close genome organization and sequence relationship between the two rodent paramyxoviruses isolated almost a decade apart and from two locations separated by more than 15,000 km. url: https://doi.org/10.1007/s00705-008-0287-3 doi: 10.1007/s00705-008-0287-3 id: cord-017817-ztp7w9yh author: Land, Walter Gottlieb title: Cell-Autonomous (Cell-Intrinsic) Stress Responses date: 2018-03-28 words: 17727.0 sentences: 855.0 pages: flesch: 40.0 cache: ./cache/cord-017817-ztp7w9yh.txt txt: ./txt/cord-017817-ztp7w9yh.txt summary: Autophagy is an evolutionarily highly conserved self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components such as defective/damaged or redundant organelles or protein aggregates are delivered to the lysosome for recycling and degradation. More recent studies then revealed that these transcription factors, notably Nrf2, are activated by Keap1 as the primary negative regulator of Nrf2, that is, a molecule that simultaneously operates as a sensor protein able to perceive dyshomeostatic Subclass IIC-4 DAMPs, for example, in terms of redox changes reflecting electrophilic stress. Strikingly, a complex relationship reportedly exists between autophagy and DAMPs in cellular adaption to stress and injury and cell death characterized by a crosstalk between autophagy induction and secretion or release of DAMPs. In fact, growing evidence indicates that autophagic mechanisms are involved in regulating release and degradation of DAMPs including CALR, HMGB1, ATP, and DNA in several cell types [37, 148, 175] . abstract: In this chapter, the role of cell-intrinsic stress responses is examined which include autophagic processes, the oxidative stress response, the heat shock response, the unfolded proteins response, and the DNA damage response. Autophagy (macroautophagy, microautophagy, and chaperone-mediated autophagy) is a self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components are delivered to the lysosome for recycling and degradation. The oxidative stress response is directed against any oxidative stress and is mediated by antioxidative defense systems including antioxidant enzymes such as superoxide dismutase, detoxifying enzymes such as glutathione peroxidase, and energy-dependent efflux pumps. The heat shock response is induced upon exposure of cells to any stress condition and characterized by emission of heat shock proteins which operate as DAMPs to maintain and restore homeostasis. The unfolded protein response is induced by any stress of the endoplasmic reticulum that is perceived by three sensor molecules. Under remediable endoplasmic reticulum stress conditions, the sensors trigger signalling pathways to resolve this stress. However, in severe irremediable endoplasmic reticulum stress, the unfolded protein response may lead to pro-inflammatory and pro-apoptotic responses resulting in regulated cell death. Finally, the DNA damage response is induced by any DNA damage that occurs in a variety of exogenous and endogenous conditions. When successful, this stress response leads to DNA repair and is associated with the emission of various DAMPs which contribute to restoration of homeostasis. When unsuccessful, the DNA damage response, like the unsuccessful unfolded protein response, can result in regulated cell death, either in form of apoptosis or necrosis. Together, the ultimate goal of all the stress responses is to maintain cellular homeostasis and ensure cell integrity. When they fail, the incidence of regulated cell death is frequently observed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122488/ doi: 10.1007/978-3-319-78655-1_18 id: cord-260708-l9w5jhsw author: Lasecka, Lidia title: The molecular biology of nairoviruses, an emerging group of tick-borne arboviruses date: 2013-12-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The nairoviruses are a rapidly emerging group of tick-borne bunyaviruses that includes pathogens of humans (Crimean-Congo hemorrhagic fever virus [CCHFV]) and livestock (Nairobi sheep disease virus [NSDV], also known as Ganjam virus), as well as a large number of viruses for which the normal vertebrate host has not been established. Studies on this group of viruses have been fairly limited, not least because CCHFV is a BSL4 human pathogen, restricting the number of labs able to study the live virus, while NSDV, although highly pathogenic in naive animals, is not seen as a threat in developed countries, making it a low priority. Nevertheless, recent years have seen significant progress in our understanding of the biology of these viruses, particularly that of CCHFV, and this article seeks to draw together our existing knowledge to generate an overall picture of their molecular biology, underlining areas of particular ignorance for future studies. url: https://www.ncbi.nlm.nih.gov/pubmed/24327094/ doi: 10.1007/s00705-013-1940-z id: cord-332811-kjgah8ts author: Lee, Do Hyun title: Immunoprophylactic effect of chicken egg yolk antibody (IgY) against a recombinant S1 domain of the porcine epidemic diarrhea virus spike protein in piglets date: 2015-06-23 words: 5898.0 sentences: 237.0 pages: flesch: 43.0 cache: ./cache/cord-332811-kjgah8ts.txt txt: ./txt/cord-332811-kjgah8ts.txt summary: title: Immunoprophylactic effect of chicken egg yolk antibody (IgY) against a recombinant S1 domain of the porcine epidemic diarrhea virus spike protein in piglets A codon-optimized PEDV S1 gene consisting of amino acid residues 25–749 was synthesized and used to establish a stable porcine cell line constitutively expressing a recombinant PEDV S1 protein containing the chicken immunoglobulin Fc fragment at its C-terminus. Moreover, oral passive immunization using chicken IgY raised against the PEDV S1 protein was found to control and prevent PED post-challenge in suckling piglets. All neonatal piglets except for animals in the control group were inoculated orally with 1 ml of the small-intestine homogenate containing 10 4 TCID 50 /ml PEDV field virus determined using real-time RT-PCR as described previously [10] . Immunoprophylactic effect of chicken egg yolk immunoglobulin (IgY) against porcine epidemic diarrhea virus (PEDV) in piglets abstract: Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine causing high mortality rates in piglets. PEDV outbreaks have occurred continuously in most swine-producing Asian countries and have recently emerged in the United States, leading to large economic losses for both the Asian and US pig industries. The spike (S) protein of PEDV consists of the S1 and S2 domains, responsible for virus binding and fusion, respectively. The involvement of the S1 domain in specific high-affinity interactions with the cellular receptor and induction of neutralizing antibodies in the natural host makes it a logical target for the development of effective vaccines and therapeutics against PEDV. Passive immunization by oral administration of egg yolk antibodies (IgY) obtained from immunized chickens provides an alternative source of specific antibodies for the prevention and treatment of PEDV in newborn piglets. In this study, we produced an IgY against the PEDV S1 protein and investigated its immunoprophylactic effect in neonatal piglets. A codon-optimized PEDV S1 gene consisting of amino acid residues 25–749 was synthesized and used to establish a stable porcine cell line constitutively expressing a recombinant PEDV S1 protein containing the chicken immunoglobulin Fc fragment at its C-terminus. The purified recombinant S1 protein was found to mediate potent immune responses in immunized hens. We next tested the ability of oral passive immunization with anti-PEDV S1 IgY to protect piglets against PEDV. Specific chicken IgY against the S1 protein was orally administered to neonatal piglets, and their responses subsequent to a virulent PEDV challenge were monitored. The results showed that oral administration of anti-PEDV S1 IgY efficiently protects neonatal piglets against PEDV, suggesting its potential as a prophylactic or therapeutic agent against acute PEDV infection. url: https://doi.org/10.1007/s00705-015-2494-z doi: 10.1007/s00705-015-2494-z id: cord-285180-32bxx94u author: Lee, Sunhee title: Functional characterization and proteomic analysis of the nucleocapsid protein of porcine deltacoronavirus date: 2015-10-02 words: 7641.0 sentences: 359.0 pages: flesch: 43.0 cache: ./cache/cord-285180-32bxx94u.txt txt: ./txt/cord-285180-32bxx94u.txt summary: Time-course Western blot analysis revealed that the PK-PDCoV-N cells stably express and accumulate robust levels of a ∼45 kDa recombinant N protein, larger than its predicted molecular weight of approximately 38 kDa possibly due to post-translational modifications and the presence of C-terminal myc and histidine tags (Fig. 1C ). To identify the differentially expressed cellular protein spots in PK-PDCoV-N cells at different time points, 10 protein spots with a statistically significant alteration, including 8 up-regulated and 2 down-regulated protein spots (Fig. 4B) , were selected and manually excised from the stained gels. These proteins showing altered expression were associated with various cellular functions including intracellular transport, metabolic processes, gene regulation, the stress response, protein synthesis, cytoskeleton networks, and cell division. Coronavirus infection of cultured cells is known to cause ER stress and to induce the UPR, which then crosstalks with various cellular signaling pathways, including mitogen-activated protein kinase cascades, autophagy, apoptosis, and innate immune responses, indicating the involvement of UPR activation in virus-host interactions and viral pathogenesis . abstract: Porcine deltacoronavirus (PDCoV) is a newly discovered enterotropic swine coronavirus that causes enteritis and diarrhea in piglets. Like other coronaviruses, PDCoV commonly contains 4 major structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Among these, the N protein is known to be the most abundant and multifunctional viral component. Therefore, as the first step toward understanding the biology of PDCoV, the present study investigated functional characteristics and expression dynamics of host proteins in a stable porcine cell line constitutively expressing the PDCoV N protein. Similar to N proteins of other coronaviruses, the PDCoV N protein was found to interact with itself to form non-covalently linked oligomers and was mainly localized to the nucleolus. We then assessed alterations in production levels of proteins in the N-expressing PK (PK-PDCoV-N) cells at different time points by means of proteomic analysis. According to the results of high-resolution two-dimensional gel electrophoresis, a total of 43 protein spots were initially found to be differentially expressed in PK-PDCoV-N cells in comparison with control PK cells. Of these spots, 10 protein spots showed a statistically significant alteration, including 8 up-regulated and 2 down-regulated protein spots and were picked for subsequent protein identification by peptide mass fingerprinting following matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The affected cellular proteins that we identified in this study were classified into the functional groups involved in various cellular processes such as cell division, metabolism, the stress response, protein biosynthesis and transport, cytoskeleton networks and cell communication. Notably, two members of the heat shock protein 70 family were found to be up-regulated in PK-PDCoV-N cells. These proteomic data will provide insights into the specific cellular response to the N protein during PDCoV infection. url: https://api.elsevier.com/content/article/pii/S0168170215002786 doi: 10.1016/j.virusres.2015.06.013 id: cord-320083-0k15w624 author: Leitão, Jorge H. title: Microbial Virulence Factors date: 2020-07-27 words: 2819.0 sentences: 140.0 pages: flesch: 39.0 cache: ./cache/cord-320083-0k15w624.txt txt: ./txt/cord-320083-0k15w624.txt summary: Microbial virulence factors encompass a wide range of molecules produced by pathogenic microorganisms, enhancing their ability to evade their host defenses and cause disease [...]. The paper focused on the discovery, properties and substrate specificity of the two proteases, their high specificity towards actin, and discussed their contribution to the invasiveness of Serratia, although further knowledge of the bacterium virulence factors and the cellular response mechanisms is required to fully understand the mechanism of Serratia invasion of the host cell [14] . The roles played by virulence factors produced by bacteria when crossing the central nervous system is also addressed, followed by the review of the specific traits of bacterial species more commonly associated with meningitis [15] . The authors also present a thorough review of the main virulence factors used by the organism, including pyolysin, fimbriae, extracellular matrix-binding proteins, neuraminidases, and ability to form biofilms [17] . From Gene to Protein-How Bacterial Virulence Factors Manipulate Host Gene Expression during Infection abstract: Microbial virulence factors encompass a wide range of molecules produced by pathogenic microorganisms, enhancing their ability to evade their host defenses and cause disease [...]. url: https://www.ncbi.nlm.nih.gov/pubmed/32727013/ doi: 10.3390/ijms21155320 id: cord-299270-fwbz3t25 author: Lemieux, M. Joanne title: Structure and function of proteins in membranes and nanodiscs date: 2020-08-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The field of membrane structural biology represents a fast-moving field with exciting developments including native nanodiscs that allow preparation of complexes of post-translationally modified proteins bound to biological lipids. This has led to conceptual advances including biological membrane:protein assemblies or “memteins” as the fundamental functional units of biological membranes. Tools including cryo-electron microscopy and X-ray crystallography are maturing such that it is becoming increasingly feasible to solve structures of large, multicomponent complexes, while complementary methods including nuclear magnetic resonance spectroscopy yield unique insights into interactions and dynamics. Challenges remain, including elucidating exactly how lipids and ligands are recognized at atomic resolution and transduce signals across asymmetric bilayers. In this special volume some of the latest thinking and methods are gathered through the analysis of a range of transmembrane targets. Ongoing work on areas including polymer design, protein labelling and microfluidic technologies will ensure continued progress on improving resolution and throughput, providing deeper understanding of this most important group of targets. url: https://api.elsevier.com/content/article/pii/S0005273620302881 doi: 10.1016/j.bbamem.2020.183445 id: cord-260869-rym2ik0o author: Lemmermeyer, Tanja title: Characterization of monoclonal antibodies against feline coronavirus accessory protein 7b date: 2016-02-29 words: 6482.0 sentences: 389.0 pages: flesch: 58.0 cache: ./cache/cord-260869-rym2ik0o.txt txt: ./txt/cord-260869-rym2ik0o.txt summary: The 7b protein has a molecular mass of $26 kDa, it is secreted from the cell and contains (i) a Cterminal KDEL-like endoplasmic reticulum (ER) retention signal, (ii) an N-terminal signal sequence of 17 amino acids and (iii) a potential N-glycosylation site at aa position 68 (Vennema et al., 1992a) . The identity of the purified protein was confirmed by SDS-PAGE and Western blotting using anti-His mAb. The protein had an apparent molecular mass of 24 kDa as judged by SDS-PAGE analysis, which is predicted for this protein, and was recognized by the His-tag-specific antibody (Fig. 1a) . Two additional minor bands in the SDS-PAGE were specifically recognized by Western blotting using the His-tag-specific mAb. These bands are consistent with a dimer and a 37-kDa degradation product, respectively, of the GST-7bDSS-His protein (Fig. 1b) . The results outlined above show that the anti-7b mAbs recognize exclusively the nonglycosylated form of the viral protein in FCoV-infected cells. abstract: Feline coronaviruses (FCoVs) encode five accessory proteins termed 3a, 3b, 3c, 7a and 7b of unknown function. These proteins are dispensable for viral replication in vitro but are supposed to play a role in virulence. In the current study, we produced and characterized 7b-specific monoclonal antibodies (mAbs). A recombinant form of the 7b protein was expressed as a fusion protein in Escherichia coli, purified by immobilized metal affinity chromatography and used as immunogen. Two hybridoma lines, 5B6 and 14D8, were isolated that expressed mAbs that recognized 7b proteins of both FCoV serotypes. Using an extensive set of N- and C-terminally truncated 7b proteins expressed in E. coli and a synthetic peptide, the binding sites of mAbs 5B6 and 14D8 were mapped to an 18-residue region that comprises the only potential N-glycosylation site of the FCoV 7b protein. The two mAbs were suitable to detect a 24-kDa protein, which represents the nonglycosylated form of 7b in FCoV-infected cells. We speculate that glycosylation of 7b is part of the viral evasion strategy to prevent an immune response against this antigenic site. url: https://api.elsevier.com/content/article/pii/S0378113515301140 doi: 10.1016/j.vetmic.2015.12.009 id: cord-290638-7ro72sv3 author: Lenstra, Johannes A. title: Antigenicity of the peplomer protein of infectious bronchitis virus date: 1989-01-31 words: 3960.0 sentences: 230.0 pages: flesch: 53.0 cache: ./cache/cord-290638-7ro72sv3.txt txt: ./txt/cord-290638-7ro72sv3.txt summary: Abstract To study the antigenic structure of the peplomer protein of the avian coronavirus infectious bronchitis virus, fragments from the peplomer gene were generated by restriction-enzyme cleavage or by limited DNase digestion and inserted in the Escherichia coli expression plasrnid pEX (Stanley and Luzio, 1984). Recombinants expressing the IBV gene fragments were selected by immunoscreening with a rabbit antiserum or, when the expression product was not recognized antigenically, by hybridization followed by gel electrophoresis of the protein expression products. Figure 2 (C) shows a Western blot of hybrid proteins screened with this MAb. The strong binding to fragments p2, s4, psl and ps2 localizes the epitope of MAb 26.1 between residues 390 and 612, the same region that is recognized by all polyclonal sera. The localization of epitopes within stretches of 10-20 residues in several coronaviruses (Fig. 4 , unpublished results) demonstrates that the binding of antibody does not depend on particular flanking sequences, and that any nativelike folding of the epitope in the hybrid protein is confined to the same small region. abstract: Abstract To study the antigenic structure of the peplomer protein of the avian coronavirus infectious bronchitis virus, fragments from the peplomer gene were generated by restriction-enzyme cleavage or by limited DNase digestion and inserted in the Escherichia coli expression plasrnid pEX (Stanley and Luzio, 1984). The antigenicity of the expression products was tested using a number of polyclonal antisera and monoclonal antibodies. The polyclonal antisera recognized different sets of epitopes in the 1162-residue sequence. The N-terminal region of one of the two subunits, S2, was recognized by all polyclonal sera and by two monoclonal antibodies. This clearly immunodominant region contains at least two adjacent or overlapping epitopes, one of which has been localized within 18 residues. The epitopes found as antigenic pEX expression products do not coincide with the regions in the S1 subunit that have been found to contain hypervariable sequences. We suggest that these regions constitute conformation dependent neutralization epitopes that cannot be detected in the pEX system. The relevance of our finclings for vaccine development is discussed. url: https://api.elsevier.com/content/article/pii/016158908990014X doi: 10.1016/0161-5890(89)90014-x id: cord-334592-54dofkxh author: Levine, Beth title: Autophagy in immunity and inflammation date: 2011-01-20 words: 10249.0 sentences: 418.0 pages: flesch: 29.0 cache: ./cache/cord-334592-54dofkxh.txt txt: ./txt/cord-334592-54dofkxh.txt summary: Moreover, p62 is required for starvation and IFN-γ-induced targeting of Fau (and perhaps other ubiquitylated protein complexes) to mycobacteria-containing phagosomes, resulting in the generation of antimycobacterial Fau-derived peptides 42 .The role of p62 in innate immunity is probably evolutionarily ancient, as the Drosophila p62 orthologue REF(2)P was originally identified in a screen for modifiers of sigma virus replication 43 . The mechanisms by which autophagy genes mediate in vivo resistance to infection are not fully understood, but are likely to involve a combination of xenophagy, other autophagy-protein-dependent effects on microbial replication or survival, activation of innate and adaptive immune responses, and/or alterations in pathogen-induced cell death (Fig. 3 ). abstract: Autophagy is an essential, homeostatic process by which cells break down their own components. Perhaps the most primordial function of this lysosomal degradation pathway is adaptation to nutrient deprivation. However, in complex multicellular organisms, the core molecular machinery of autophagy — the 'autophagy proteins' — orchestrates diverse aspects of cellular and organismal responses to other dangerous stimuli such as infection. Recent developments reveal a crucial role for the autophagy pathway and proteins in immunity and inflammation. They balance the beneficial and detrimental effects of immunity and inflammation, and thereby may protect against infectious, autoimmune and inflammatory diseases. url: https://doi.org/10.1038/nature09782 doi: 10.1038/nature09782 id: cord-021772-5v4gor2v author: Levine, Gwendolyn J. title: Cerebrospinal Fluid and Central Nervous System Cytology date: 2019-05-31 words: 12646.0 sentences: 768.0 pages: flesch: 46.0 cache: ./cache/cord-021772-5v4gor2v.txt txt: ./txt/cord-021772-5v4gor2v.txt summary: 45, 46 In a recent study of 106 canine CSF samples without pleocytosis (TNCC <5/μL) but containing at least 500 RBCs/μL, the mean percentage of neutrophils (45.2% versus 5.7%), percentage of samples with eosinophils present (36.8% versus 6.8%), and mean protein concentration (40 mg/dL versus 26 mg/dL) were found to be significantly increased in the samples with blood contamination when compared with controls. 4 A study of cats with CNS cryptococcosis showed organisms in 9 of 11 of the CSF samples, and a majority of cases (9 of 10) had neutrophilic pleocytosis and increased protein concentration (8 of 10). A case series of five cats showed CSF ranging from normal to marked neutrophilic pleocytosis with moderately elevated protein concentration and variable correlation to clinical outcome. 85 A study of eight dogs with natural infection (confirmed by CNS tissue-PCR and histopathology) showed lymphocytic pleocytosis in all samples and normal protein concentrations. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151995/ doi: 10.1016/b978-0-323-53314-0.00014-6 id: cord-017968-17d37a2z author: Lewinski, Martin title: Systems Approaches to Map In Vivo RNA–Protein Interactions in Arabidopsis thaliana date: 2018-08-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Proteins that specifically interact with mRNAs orchestrate mRNA processing steps all the way from transcription to decay. Thus, these RNA-binding proteins represent an important control mechanism to double check which proportion of nascent pre-mRNAs is ultimately available for translation into distinct proteins. Here, we discuss recent progress to obtain a systems-level understanding of in vivo RNA–protein interactions in the reference plant Arabidopsis thaliana using protein-centric and RNA-centric methods as well as combined protein binding site and structure probing. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122672/ doi: 10.1007/978-3-319-92967-5_5 id: cord-321386-u1imic5l author: Li, Chun title: Protein Sequence Comparison and DNA-binding Protein Identification with Generalized PseAAC and Graphical Representation date: 2018-02-17 words: 5503.0 sentences: 311.0 pages: flesch: 59.0 cache: ./cache/cord-321386-u1imic5l.txt txt: ./txt/cord-321386-u1imic5l.txt summary: METHODS: Based on two physicochemical properties of amino acids, a protein primary sequence was converted into a three-letter sequence, and then a graph without loops and multiple edges and its geometric line adjacency matrix were obtained. A generalized PseAAC (pseudo amino acid composition) model was thus constructed to characterize a protein sequence numerically. In addition, a generalized PseAAC based SVM (support vector machine) model was developed to identify DNA-binding proteins. Also, we develop a SVM (support vector machine) model using the generalized PseAAC to identify DNA-binding and non-binding proteins on three datasets. By combining these elements with the conventional amino acid composition (AAC), a dimensional feature vector can be constructed to numerically characterize a protein sequence: , By combining these elements with the frequencies of occurrence of 20 standard amino acids and their three representative letters, a generalized PseAAC model of a protein sequence was constructed. Numerical characterization of protein sequences based on the generalized Chou''s pseudo amino acid composition abstract: AIM AND OBJECTIVE: The rapid increase in the amount of protein sequence data available leads to an urgent need for novel computational algorithms to analyze and compare these sequences. This study is undertaken to develop an efficient computational approach for timely encoding protein sequences and extracting the hidden information. METHODS: Based on two physicochemical properties of amino acids, a protein primary sequence was converted into a three-letter sequence, and then a graph without loops and multiple edges and its geometric line adjacency matrix were obtained. A generalized PseAAC (pseudo amino acid composition) model was thus constructed to characterize a protein sequence numerically. RESULTS: By using the proposed mathematical descriptor of a protein sequence, similarity comparisons among β-globin proteins of 17 species and 72 spike proteins of coronaviruses were made, respectively. The resulting clusters agreed well with the established taxonomic groups. In addition, a generalized PseAAC based SVM (support vector machine) model was developed to identify DNA-binding proteins. Experiment results showed that our method performed better than DNAbinder, DNA-Prot, iDNA-Prot and enDNA-Prot by 3.29-10.44% in terms of ACC, 0.056-0.206 in terms of MCC, and 1.45-15.76% in terms of F1M. When the benchmark dataset was expanded with negative samples, the presented approach outperformed the four previous methods with improvement in the range of 2.49-19.12% in terms of ACC, 0.05-0.32 in terms of MCC, and 3.82-33.85% in terms of F1M. CONCLUSION: These results suggested that the generalized PseAAC model was very efficient for comparison and analysis of protein sequences, and very competitive in identifying DNA-binding proteins. url: https://doi.org/10.2174/1386207321666180130100838 doi: 10.2174/1386207321666180130100838 id: cord-323331-80d01l6f author: Li, Jie title: Golgi Structure and Function in Health, Stress, and Diseases date: 2019-01-01 words: 13448.0 sentences: 930.0 pages: flesch: 50.0 cache: ./cache/cord-323331-80d01l6f.txt txt: ./txt/cord-323331-80d01l6f.txt summary: Mechanistically, GRASP proteins form homodimers via the N-terminal PDZ domains, and dimers from adjacent Golgi cisternae further oligomerize in trans and function as the "glue" that tethers the cisternae into a stack (Wang et al. Other than the well-studied GRASP65-GM130 and GM130-p115-giantin complexes, the GRIP domain containing golgins are another group of proteins associated with the Golgi structure. Depletion of αSNAP in p53 null or Bax null cells still results in apoptosis, indicating that the anti-apoptotic function is independent of p53 and Bax. Interestingly, αSNAP depletion induces apoptosis independent of the cleavage of Golgi proteins such as GRASP65, golgin-160, and p115 but rather by dysregulation of ER-Golgi vesicle cycling and possibly through ER stress (Naydenov et al. The coiled-coil membrane protein golgin-84 is a novel rab effector required for Golgi ribbon formation Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis abstract: The Golgi apparatus is a central intracellular membrane-bound organelle with key functions in trafficking, processing, and sorting of newly synthesized membrane and secretory proteins and lipids. To best perform these functions, Golgi membranes form a unique stacked structure. The Golgi structure is dynamic but tightly regulated; it undergoes rapid disassembly and reassembly during the cell cycle of mammalian cells and is disrupted under certain stress and pathological conditions. In the past decade, significant amount of effort has been made to reveal the molecular mechanisms that regulate the Golgi membrane architecture and function. Here we review the major discoveries in the mechanisms of Golgi structure formation, regulation, and alteration in relation to its functions in physiological and pathological conditions to further our understanding of Golgi structure and function in health and diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/31435807/ doi: 10.1007/978-3-030-23173-6_19 id: cord-294575-kky8j9oy author: Li, Jieqiong title: Characterization of plasma proteins in children of different Mycobacterium tuberculosis infection status using label-free quantitative proteomics date: 2017-09-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an infectious disease found worldwide. Children infected with MTB are more likely to progress to active TB (ATB); however, the molecular mechanism behind this process has long been a mystery. We employed the label-free quantitative proteomic technology to identify and characterize differences in plasma proteins between ATB and latent TB infection (LTBI) in children. To detect differences that are indicative of MTB infection, we first selected proteins whose expressions were markedly different between the ATB and LTBI groups and the control groups (inflammatory disease control (IDC) and healthy control (HC) groups). A total of 521 proteins differed (> 1.5-fold or < 0.6-fold) in the LTBI group, and 318 proteins in the ATB group when compared with the control groups. Of these, 49 overlapping proteins were differentially expressed between LTBI and ATB. Gene Ontology (GO) analysis revealed most proteins had a cellular and organelle distribution. The MTB infection status was mainly related to differences in binding, cellular and metabolic processes. XRCC4, PCF11, SEMA4A and ATP11A were selected and further verified by qPCR and western blot. At the mRNA level, the expression of XRCC4, PCF11and SEMA4A presented an increased trend in ATB group compare with LTBI. At the protein level, the expression of all these proteins by western blot in ATB/LTBI was consistent with the trends from proteomic detection. Our results provide important data for future mechanism studies and biomarker selection for MTB infection in children. url: https://doi.org/10.18632/oncotarget.21179 doi: 10.18632/oncotarget.21179 id: cord-288101-pij16jaa author: Li, Jun-Yu title: Proteomic analysis of the response of porcine adrenal gland to heat stress date: 2019-02-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Heat stress (HS) and its associated pathologies are major challenges facing the pig industry in southern China, and are responsible for large economic losses. However, the molecular mechanisms governing the abnormal secretion of HS-responsive hormones, such as glucocorticoids, are not fully understood. The goal of this study was to investigate differentially expressed proteins (DEPs) in the adrenal glands of pigs, and to elucidate changes in the immune neuroendocrine system in pigs following HS. Through a functional proteomics approach, we identified 1202 peptides, corresponding to 415 proteins. Of these, we found 226 DEPs between heat-stressed and control porcine adrenal gland tissue; 99 of these were up-regulated and 127 were down-regulated in response to HS. These DEPs included proteins involved in substrate transport, cytoskeletal changes, and stress responses. Ingenuity Pathway Analysis was used to identify the subcellular characterization, functional pathway involvement, regulatory networks, and upstream regulators of the identified proteins. Functional network and pathway analyses may provide insights into the complexity and dynamics of HS-host interactions, and may accelerate our understanding of the mechanisms of HS. url: https://api.elsevier.com/content/article/pii/S0034528818310993 doi: 10.1016/j.rvsc.2018.11.004 id: cord-310680-klywz85w author: Li, Qihan title: The interaction of the SARS coronavirus non-structural protein 10 with the cellular oxido-reductase system causes an extensive cytopathic effect date: 2005-04-06 words: 4397.0 sentences: 210.0 pages: flesch: 53.0 cache: ./cache/cord-310680-klywz85w.txt txt: ./txt/cord-310680-klywz85w.txt summary: The gene for the SARS-CoV non-structural protein 10, which is located in the open reading frame of pp1a/pp1ab gene, was synthesized and used to screen for the specific cellular gene coding for the protein interacting with this nsp10 protein in a human embryo lung cDNA library using a yeast trap method. The pathological analysis of the lung tissue from the deceased patients revealed severe Abbreviations: SARS-CoV, severe acute respiratory syndrome coronavirus; BTF3, basic transcription factor-3; ATF5, activation transcription factor-5; NADH, nicotinamide adenine dinucleotide dehydrogenase; FBS, fetal bovine serum; DMEM, double minimal essential media; QDO, quartdrop-out; NC, nitrocellulose; HE, hematoxyline and eosin method; GFP, green fluorescence protein; GST, glutathione S-transferase * Corresponding author. To further investigate the contribution of this interaction to the cytopathic effect of SARS-CoV, a detection series of mitochondrial function and the activity of the oxido-reductase system in the human embryo lung fibroblast transfected with the nsp10 gene was performed. abstract: The pathological mechanism of SARS-CoV infection was investigated. The gene for the SARS-CoV non-structural protein 10, which is located in the open reading frame of pp1a/pp1ab gene, was synthesized and used to screen for the specific cellular gene coding for the protein interacting with this nsp10 protein in a human embryo lung cDNA library using a yeast trap method. The results indicated that apart from the two subunits of cellular RNA polymerase complex, BTF3 and ATF5, this nsp10 protein was also able to interact specifically with the NADH 4L subunit and cytochrome oxidase II. Further study revealed that the activity of the NADH-cytochrome was altered and the inner mitochondrial membrane was depolarized in the transfected human embryo lung fibroblast by the nsp10 protein gene. The cytopathic effect of the Coronavirus 229E strain appeared more extensive in these cells than in the control cells. url: https://www.ncbi.nlm.nih.gov/pubmed/16157265/ doi: 10.1016/j.jcv.2004.12.019 id: cord-024989-0o6agnrc author: Li, Qihao title: Prediction and analysis of key protein structures of 2019-nCoV date: 2020-05-12 words: 3244.0 sentences: 172.0 pages: flesch: 58.0 cache: ./cache/cord-024989-0o6agnrc.txt txt: ./txt/cord-024989-0o6agnrc.txt summary: Aim: The purpose of this study was to predict and analyze the structure and function of 2019-novel Coronavirus (nCoV) key proteins. Differential key protein structure analysis of 2019-nCoV Although some amino acids were inserted in two positions of nsp3 in orf1ab [23] , the insertion sites were in the nsp3b and nsp3c regions, which are mainly related to the binding reaction of nucleic acids. Back-mutating mutant amino acids to study the functional change of RBD of S protein In order to study the effect of interactional amino acid changes in 2019-nCoV-ACE2 binding region RBD, we mutated the changed three amino acid residues (Glu 470 , Gln 484 and Asn 487 ) within the RBD structure back to the original amino acids. • We elaborated the sequence and structure differences in each key protein of 2019-nCoV and other bat SARS coronaviruses (CoVs). abstract: Aim: The purpose of this study was to predict and analyze the structure and function of 2019-novel Coronavirus (nCoV) key proteins. Materials & methods: We obtained the structure and sequence of proteins from related databases and studied them through multiple sequence alignment, homology modeling, sequence analysis, virtual screening, reverse mutation, protein structure overlap and surface property analysis. Results & conclusion: We found no significant changes in envelope protein, membrane protein, nucleocapsid protein and key proteases in open reading frame 1ab, and predicted results of proteins and performed molecular dynamics simulations. Based on the surface properties of spike protein and docking results with angiotensin-converting enzyme 2, we believe that the binding ability of spike protein to angiotensin-converting enzyme 2 may be similar to SARS. These studies will help us in fighting 2019-nCoV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236793/ doi: 10.2217/fvl-2020-0020 id: cord-327000-oyg3oyx1 author: Li, Shasha title: Porcine Epidemic Diarrhea Virus and the Host Innate Immune Response date: 2020-05-11 words: 11098.0 sentences: 688.0 pages: flesch: 48.0 cache: ./cache/cord-327000-oyg3oyx1.txt txt: ./txt/cord-327000-oyg3oyx1.txt summary: This review highlights the immune evasion mechanisms employed by PEDV, which provides insights for the better understanding of PEDV-host interactions and developing effective vaccines and antivirals against CoVs. Porcine epidemic diarrhea virus (PEDV) is the etiological agent of porcine epidemic diarrhea (PED) that causes an acute and highly contagious enteric disease of swine characterized by vomiting, diarrhea, dehydration, and anorexia in pigs of all ages, especially resulting in severe diarrhea and high mortality rate in piglets. Nsp3 is the largest nsp protein, containing two papain-like protease (PLP1 and PLP2) domains, of which PEDV PLP2 acts as a viral deubiquitinase (DUB), to negatively regulate type I IFN signaling [80] . The evasive strategies utilized by PEDV are classified into four major types: (1) inhibition of RLRs-mediated IFN production pathways, (2) inhibition of the activation of transcription factors responsible for IFN induction, (3) disruption of the signal cascades induced by IFN, and (4) hiding its viral RNA to avoid the exposure of viral RNA to immune sensors. abstract: Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus (CoV), is the causative agent of porcine epidemic diarrhea (PED). PED causes lethal watery diarrhea in piglets, which has led to substantial economic losses in many countries and is a great threat to the global swine industry. Interferons (IFNs) are major cytokines involved in host innate immune defense, which induce the expression of a broad range of antiviral effectors that help host to control and antagonize viral infections. PEDV infection does not elicit a robust IFN response, and some of the mechanisms used by the virus to counteract the host innate immune response have been unraveled. PEDV evades the host innate immune response by two main strategies including: 1) encoding IFN antagonists to disrupt innate immune pathway, and 2) hiding its viral RNA to avoid the exposure of viral RNA to immune sensors. This review highlights the immune evasion mechanisms employed by PEDV, which provides insights for the better understanding of PEDV-host interactions and developing effective vaccines and antivirals against CoVs. url: https://doi.org/10.3390/pathogens9050367 doi: 10.3390/pathogens9050367 id: cord-007208-wnkjdg6y author: Li, Sheng-Hsiang title: Demonstration of a Glycoprotein Derived From the Ceacam10 Gene in Mouse Seminal Vesicle Secretions(1) date: 2005-09-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: CEACAM10 was purified from mouse seminal vesicle secretions by a series of purification steps that included ion exchange chromatography on a DEAE-Sephacel column and ion exchange high-performance liquid chromatography on a sulfopropyl column. It was shown to be a 36-kDa glycoprotein with an N-linked carbohydrate moiety. The circular dichromoism spectrum of CEACAM10 in 50 mM phosphate buffer at pH 7.4 appeared as one negative band arising from the β form at 217 nm. CEACAM10 was expressed predominantly in seminal vesicles of adult mice. Both CEACAM10 and its mRNA were demonstrated on the luminal epithelium of the mucosal folds in the seminal vesicle. The amount of Ceacam10 mRNA in the seminal vesicle was correlated with the stage of animal maturation. Castration of adult mice resulted in cessation of Ceacam10 expression, while treatment of castrated mice with testosterone propionate in corn oil restored Ceacam10 expression in the seminal vesicle. During the entire course of pregnancy, Ceacam10 might be silent in the embryo. A cytochemical study illustrated the presence of the CEACAM10 binding region on the entire surface of mouse sperm. CEACAM10-sperm binding greatly enhanced sperm motility in vitro. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109865/ doi: 10.1095/biolreprod.105.039651 id: cord-018276-elb93kp6 author: Li, Shitao title: Proteomics Defines Protein Interaction Network of Signaling Pathways date: 2012-12-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Protein interactions play fundamental roles in signaling transduction. Analysis of protein–protein interaction (PPI) has contributed numerous insights to the understanding of the regulation of signal pathways. Different approaches have been used to discover PPI and characterize protein complexes. In addition to conventional PPI methods, such as yeast two-hybrid (YTH), affinity purification coupled with mass spectrometry (AP-MS) is emerging as an important and popular tool to unravel protein complex and elucidate protein function through the interaction partners. With the AP-MS method, protein complexes are prepared first by affinity purification directly from cell lysates, followed by characterization of their components by mass spectrometry. In contrast to most PPI methods, AP-MS reflects PPI under near physiological conditions in the relevant organism and cell type. AP-MS is also able to probe dynamic PPI dependent on protein posttranslational modifications, which is common for signal transduction. AP-MS mapping protein interaction network of various signal pathways has dramatically increased in recent years. Here, I’ll present the strategies toward obtaining an interactome map of signal pathway and the methodology, detailed protocols, and perspectives of AP-MS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123116/ doi: 10.1007/978-94-007-5811-7_2 id: cord-003761-ikni2acz author: Li, Zengbin title: Biological Function and Application of Picornaviral 2B Protein: A New Target for Antiviral Drug Development date: 2019-06-04 words: 6425.0 sentences: 331.0 pages: flesch: 39.0 cache: ./cache/cord-003761-ikni2acz.txt txt: ./txt/cord-003761-ikni2acz.txt summary: In this review, we mainly summarize recent research data on the viroporin or viroporin-like activity of 2B proteins, which affects the biological function of the membrane, regulates cell death, and affects the host immune response. In particular, the 2B protein may change the Ca 2+ concentration to regulate autophagy and apoptosiswhich are distinct cell death mechanisms controlled by the virus to effectively evade the host immunity, thereby promoting viral replication and release [48] [49] [50] [51] [52] . Thus, the main points of focus for research on the structure and function of the 2B protein toward ultimate drug development are: (1) mechanism of increasing membrane permeability to disturb the ion balance, (2) regulation of autophagy and apoptosis, (3) inhibition of the host immune response, and (4) promotion of viral replication and release. abstract: Picornaviruses are associated with acute and chronic diseases. The clinical manifestations of infections are often mild, but infections may also lead to respiratory symptoms, gastroenteritis, myocarditis, meningitis, hepatitis, and poliomyelitis, with serious impacts on human health and economic losses in animal husbandry. Thus far, research on picornaviruses has mainly focused on structural proteins such as VP1, whereas the non-structural protein 2B, which plays vital roles in the life cycle of the viruses and exhibits a viroporin or viroporin-like activity, has been overlooked. Viroporins are viral proteins containing at least one amphipathic α-helical structure, which oligomerizes to form transmembrane hydrophilic pores. In this review, we mainly summarize recent research data on the viroporin or viroporin-like activity of 2B proteins, which affects the biological function of the membrane, regulates cell death, and affects the host immune response. Considering these mechanisms, the potential application of the 2B protein as a candidate target for antiviral drug development is discussed, along with research challenges and prospects toward realizing a novel treatment strategy for picornavirus infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630369/ doi: 10.3390/v11060510 id: cord-340746-icuzy3vp author: Liang, Yunfei title: Comprehensive Antibody Epitope Mapping of the Nucleocapsid Protein of Severe Acute Respiratory Syndrome (SARS) Coronavirus: Insight into the Humoral Immunity of SARS date: 2005-08-01 words: 8408.0 sentences: 374.0 pages: flesch: 47.0 cache: ./cache/cord-340746-icuzy3vp.txt txt: ./txt/cord-340746-icuzy3vp.txt summary: We identified the immunodominant antigenic sites responsible for the antibodies in sera from SARS patients and antisera from small animals and differentiated the linear from the conformational antibody-combining sites comprising the natural epitopes by use of yeast surface display. The full-length SARS-CoV N protein (amino acids 1-422) was expressed on the yeast cell surface, as indicated by reactivity of the Xpress epitope tag with the anti-Xpress antibody (Fig. 2) . We used heat denaturation of the fusion proteins tethered to the EBY100 yeast cell surface to categorize the specific linear and conformational SARS-CoV N protein mAb epitopes (35, 36 ) . Our subsequent determination of the antigenic structures of the N protein responsible for antibodies in polyclonal antisera from immunized mice and sera from convalescent SARS patients demonstrated the immunogenic specificity of 3 conformational (amino acids 1-69, 68 -213, and 337-422) and 3 linear (amino acids 1-69, 121-213, and 337-422) epitopes (Fig. 1C) . abstract: Background: The epidemic outbreak of severe acute respiratory syndrome (SARS) posed a worldwide threat to public health and economic stability. Although the pandemic has been contained, concerns over its recurrence remain. It is essential to identify specific diagnostic agents and antiviral vaccine candidates to fight this highly contagious disease. Methods: We generated 14 monoclonal antibodies (mAbs) specific to the SARS coronavirus (SARS-CoV) nucleocapsid (N) protein and used these to thoroughly map the N protein antigenic determinants. We identified the immunodominant antigenic sites responsible for the antibodies in sera from SARS patients and antisera from small animals and differentiated the linear from the conformational antibody-combining sites comprising the natural epitopes by use of yeast surface display. Results: We identified 5 conformational and 3 linear epitopes within the entire N protein; 3 conformational and 3 linear epitopes were immunodominant. The antibody responses to the N protein fragments in mammalian sera revealed that 3 regions of the N protein are strong antigenic domains. We expanded the specificity of the N protein epitope and identified 4 novel conformational epitopes (amino acids 1–69, 68–213, 212–341, and 337–422). Conclusion: The antigenic structures identified for the SARS-CoV N protein, the epitope-specific mAbs, and the serum antibody profile in SARS patients have potential use in the clinical diagnosis and understanding of the protective immunity to SARS-CoV. url: https://www.ncbi.nlm.nih.gov/pubmed/15976093/ doi: 10.1373/clinchem.2005.051045 id: cord-258489-pyfc7jde author: Lico, Chiara title: Viral vectors for production of recombinant proteins in plants date: 2008-03-10 words: 11091.0 sentences: 527.0 pages: flesch: 39.0 cache: ./cache/cord-258489-pyfc7jde.txt txt: ./txt/cord-258489-pyfc7jde.txt summary: In this review, we will focus on transient production strategies using plant viral expression systems, with a particular focus on the variety of proteins produced, and their applications. The unique properties of viruses such as ease of manipulation, high level amplification, site specific recombination, strong infectivity, enhanced translation and compact and repetitive morphological structure have enabled their broad application, from basic research to product development, including the generation of robust expression systems. From the discovery of viruses in 1898 (tobacco mosaic virus, TMV) (Bos, 1999) , to the first demonstration of RNAs role in virus replication by turnip yellow mosaic virus (TYMV) (Matthews, 1989) , to the very recent discovery of gene silencing and its implication in host response to infection, gene regulation and transgene expression (Baulcombe, 1999; Lu et al., 2003; Waterhouse and Helliwell, 2003) , plant virology has played a crucial role in the understanding of the most fundamental concepts of modern biology. Thanks to the recent improvements of viral-based vectors, mAbs have been produced with transient expression systems to quickly achieve much higher production levels along with other complex proteins. abstract: Global demand for recombinant proteins has steadily accelerated for the last 20 years. These recombinant proteins have a wide range of important applications, including vaccines and therapeutics for human and animal health, industrial enzymes, new materials and components of novel nano‐particles for various applications. The majority of recombinant proteins are produced by traditional biological “factories,” that is, predominantly mammalian and microbial cell cultures along with yeast and insect cells. However, these traditional technologies cannot satisfy the increasing market demand due to prohibitive capital investment requirements. During the last two decades, plants have been under intensive investigation to provide an alternative system for cost‐effective, highly scalable, and safe production of recombinant proteins. Although the genetic engineering of plant viral vectors for heterologous gene expression can be dated back to the early 1980s, recent understanding of plant virology and technical progress in molecular biology have allowed for significant improvements and fine tuning of these vectors. These breakthroughs enable the flourishing of a variety of new viral‐based expression systems and their wide application by academic and industry groups. In this review, we describe the principal plant viral‐based production strategies and the latest plant viral expression systems, with a particular focus on the variety of proteins produced and their applications. We will summarize the recent progress in the downstream processing of plant materials for efficient extraction and purification of recombinant proteins. J. Cell. Physiol. 216: 366–377, 2008. © 2008 Wiley‐Liss, Inc. url: https://www.ncbi.nlm.nih.gov/pubmed/18330886/ doi: 10.1002/jcp.21423 id: cord-294945-hcf7gsv8 author: Lin, K.H. title: Comparative proteomic analysis of cauliflower under high temperature and flooding stresses date: 2015-02-12 words: 8221.0 sentences: 414.0 pages: flesch: 49.0 cache: ./cache/cord-294945-hcf7gsv8.txt txt: ./txt/cord-294945-hcf7gsv8.txt summary: The objectives of this study were to identify the proteins that were differentially regulated and the physiological changes that occurred during different time periods in ''H41'', ''H69'', and ''H71'' when responding to treatments of flooding, 40 °C, and both stresses combined. By the comparative proteomic analysis, 85 protein peaks that were differentially expressed in response to combination treatments at 0, 6, and 24 h, 69 (33 in ''H41'', 29 in ''H69'', and 9 in ''H71'') were identified, of which were cultivar specific. Compared to NFC treatment at 0 h, NFH treatment for 6 h showed that the abundances of peaks 271 (phosphoserine aminotransferase), 272 (imidazole glycerol phosphate synthase subunit hisF), Table 6 Identification of differentially expressed proteins found in cauliflower ''H71'' plants by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in comparison to combination treatments for 0 and 6 h. abstract: High-temperature and waterlogging are major abiotic stresses that affect the yield and quality of cauliflower. Cauliflower cultivars ‘H41’ and ‘H69’ are tolerant to high temperature and flooding, respectively; however, ‘H71’ is sensitive to both stresses. The objectives of this study were to identify the proteins that were differentially regulated and the physiological changes that occurred during different time periods in ‘H41’, ‘H69’, and ‘H71’ when responding to treatments of flooding, 40 °C, and both stresses combined. Changes in the leaf proteome were analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and identified by Mascot peptide mass fingerprint (PMF) and database searching. Stress treatments caused significant reductions in electrolyte leakage, chlorophyll fluorescence Fv/Fm, chlorophyll content, and water potential as stress times were prolonged. By the comparative proteomic analysis, 85 protein peaks that were differentially expressed in response to combination treatments at 0, 6, and 24 h, 69 (33 in ‘H41’, 29 in ‘H69’, and 9 in ‘H71’) were identified, of which were cultivar specific. Differentially regulated proteins predominantly functioned in photosynthesis and to a lesser extent in energy metabolism, cellular homeostasis, transcription and translation, signal transduction, and protein biosynthesis. This is the first report that utilizes proteomics to discover changes in the protein expression profile of cauliflower in response to heat and flooding. url: https://doi.org/10.1016/j.scienta.2014.12.013 doi: 10.1016/j.scienta.2014.12.013 id: cord-312741-0au4nctt author: Lin, Panpan title: Coronavirus in human diseases: Mechanisms and advances in clinical treatment date: 2020-10-01 words: 14665.0 sentences: 840.0 pages: flesch: 42.0 cache: ./cache/cord-312741-0au4nctt.txt txt: ./txt/cord-312741-0au4nctt.txt summary: 160, 161 Once the PAMPs from invaded viruses are detected, RIG-I and MDA5 interact with the mitochondrial antiviral signaling protein (MAVs) that is a mitochondrial membrane-bound F I G U R E 2 Escape mechanisms of innate immune response of SARS-CoV and MERS-CoV adaptor molecule, followed by the activation of several kinase complexes and multiple subsequent transcription factors (IRF3, IRF7, and NF-κB). Antiviral peptides analogous derived from these regions exhibited inhibition to the spike protein-mediated cell-cell fusion and viral entry in viruses such as SARS-CoV, MERS-CoV, as well as HCoV-229E. Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein abstract: Coronaviruses (CoVs), a subfamily of coronavirinae, are a panel of single‐stranded RNA virus. Human coronavirus (HCoV) strains (HCoV‐229E, HCoV‐OC43, HCoV‐HKU1, HCoV‐NL63) usually cause mild upper respiratory diseases and are believed to be harmless. However, other HCoVs, associated with severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID‐19, have been identified as important pathogens due to their potent infectivity and lethality worldwide. Moreover, currently, no effective antiviral drugs treatments are available so far. In this review, we summarize the biological characters of HCoVs, their association with human diseases, and current therapeutic options for the three severe HCoVs. We also highlight the discussion about novel treatment strategies for HCoVs infections. url: https://www.ncbi.nlm.nih.gov/pubmed/33173860/ doi: 10.1002/mco2.26 id: cord-279463-bli8hwda author: Lipp, Joachim title: The membrane-spanning segment of invariant chain (Iγ) contains a potentially cleavable signal sequence date: 1986-09-26 words: 6276.0 sentences: 367.0 pages: flesch: 62.0 cache: ./cache/cord-279463-bli8hwda.txt txt: ./txt/cord-279463-bli8hwda.txt summary: As type II membrane proteins contain only a single stretch of hydrophobic amino acid residues, this might function as a signal for membrane insertion as well as a membrane anchor (Markoff et al., 1984; Spiess and Lodish, 1986) . plycat is an in-frame fusion between the 5'' region of ly encoding the cytoplas, mic, membrane-spanning segment plus 12 amino acids of the exoplasmic portion of ly and the gene encoding the cytoplasmic protein chloramphenicol acetyltransferase (CAT). After protease digestion in the presence of microsomal membranes, lyCAT* is reduced in molecular weight by about 2 kd, suggesting that it exposes 20-30 amino acid residues on the cytoplasmic side ( Figure 3 , lanes 2 and 3). This signal sequence is located in the amino-terminal half of the membrane-spanning segment, and it is cleaved when the preceding cytoplasmic domain is removed. abstract: Abstract The human invariant chain (Iγ) of class II histocompatibility antigens spans the membrane of the endoplasmic reticulum once. It exposes a small amino-terminal domain on the cytoplasmic side and a carboxyterminal, glycosylated domain on the exoplasmic side of the membrane. When the exoplasmic domain of Iγ is replaced by the cytoplasmic protein chloramphenicol acetyltransferase (CAT), CAT becomes the exoplasmic, glycosylated domain of the resulting membrane protein IγCAT∗. Deletion of the hydrophilic cytoplasmic domain from IγCAT gives rise to a secreted protein from which an amino-terminal segment is cleaved, most likely by signal peptidase. We conclude that the membrane-spanning region of Iγ contains a signal sequence in its amino-terminal half and that hydrophilic residues at the amino-terminal end of a signal sequence can determine cleavage by signal peptidase. url: https://www.ncbi.nlm.nih.gov/pubmed/3530500/ doi: 10.1016/0092-8674(86)90710-5 id: cord-000708-iuo2cw23 author: Lippé, Roger title: Deciphering Novel Host–Herpesvirus Interactions by Virion Proteomics date: 2012-05-28 words: 5052.0 sentences: 261.0 pages: flesch: 43.0 cache: ./cache/cord-000708-iuo2cw23.txt txt: ./txt/cord-000708-iuo2cw23.txt summary: These studies include the alphaherpesvirinae herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV; Loret et al., 2008; Kramer et al., 2011) , the betaherpesvirinae human and murine cytomegaloviruses (HCMV and MCMV, respectively; Kattenhorn et al., 2004; Varnum et al., 2004) and the gammaherpesvirinae Kaposi sarcoma herpesvirus (KSHV), gamma herpesvirus 68 (γHV68), Epstein-Barr virus (EBV), and Alcelaphine (Bortz et al., 2003; Johannsen et al., 2004; Bechtel et al., 2005; Zhu et al., 2005; Dry et al., 2008) . Cellular stress rather than stage of the cell cycle enhances the replication and plating efficiencies of herpes simplex virus type 1 ICP0-viruses Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0 Herpes simplex virus 1 alpha regulatory protein ICP0 interacts with and stabilizes the cell cycle regulator cyclin D3 Identification and functional evaluation of cellular and viral factors involved in the alteration of nuclear architecture during herpes simplex virus 1 infection abstract: Over the years, a vast array of information concerning the interactions of viruses with their hosts has been collected. However, recent advances in proteomics and other system biology techniques suggest these interactions are far more complex than anticipated. One particularly interesting and novel aspect is the analysis of cellular proteins incorporated into mature virions. Though sometimes considered purification contaminants in the past, their repeated detection by different laboratories suggests that a number of these proteins are bona fide viral components, some of which likely contribute to the viral life cycles. The present mini review focuses on cellular proteins detected in herpesviruses. It highlights the common cellular functions of these proteins, their potential implications for host–pathogen interactions, discusses technical limitations, the need for complementing methods and probes potential future research avenues. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390586/ doi: 10.3389/fmicb.2012.00181 id: cord-013046-r6dtiu97 author: Liu, Bin title: Combining evolutionary information extracted from frequency profiles with sequence-based kernels for protein remote homology detection date: 2014-02-15 words: 6945.0 sentences: 347.0 pages: flesch: 52.0 cache: ./cache/cord-013046-r6dtiu97.txt txt: ./txt/cord-013046-r6dtiu97.txt summary: title: Combining evolutionary information extracted from frequency profiles with sequence-based kernels for protein remote homology detection For instance, the kernel combination methodology (VBKC) (Damoulas and Girolami, 2008 ) used a single multiclass kernel machine to combine various kernels based on different feature spaces; SVM-physicochemical distance transformation (PDT) (Liu et al., 2012) combined the amino acid physicochemical properties and the profile features via PDT to incorporate the local sequence-order information of the entire protein sequences. The results obtained by these four methods on the SCOP benchmark are listed in Supplementary Table S1 of Supplementary Material S4, from which we can see that the current method outperforms SVM-Top-n-gram-combine-LSA (Liu et al., 2008) , SVM-PDT-Profile (Liu et al., 2012) and BioSVM-2L (Muda et al., 2011) and is highly comparable with Profile (Kuang et al., 2005) and HHSearch (So¨ding, 2005) , indicating that the profile-based protein representation is a promising approach to extract the evolutionary information from frequency profiles for protein remote homology detection. Protein remote homology detection by combining Chou''s pseudo amino acid composition and profile-based protein representation abstract: Motivation: Owing to its importance in both basic research (such as molecular evolution and protein attribute prediction) and practical application (such as timely modeling the 3D structures of proteins targeted for drug development), protein remote homology detection has attracted a great deal of interest. It is intriguing to note that the profile-based approach is promising and holds high potential in this regard. To further improve protein remote homology detection, a key step is how to find an optimal means to extract the evolutionary information into the profiles. Results: Here, we propose a novel approach, the so-called profile-based protein representation, to extract the evolutionary information via the frequency profiles. The latter can be calculated from the multiple sequence alignments generated by PSI-BLAST. Three top performing sequence-based kernels (SVM-Ngram, SVM-pairwise and SVM-LA) were combined with the profile-based protein representation. Various tests were conducted on a SCOP benchmark dataset that contains 54 families and 23 superfamilies. The results showed that the new approach is promising, and can obviously improve the performance of the three kernels. Furthermore, our approach can also provide useful insights for studying the features of proteins in various families. It has not escaped our notice that the current approach can be easily combined with the existing sequence-based methods so as to improve their performance as well. Availability and implementation: For users’ convenience, the source code of generating the profile-based proteins and the multiple kernel learning was also provided at http://bioinformatics.hitsz.edu.cn/main/∼binliu/remote/ Contact: bliu@insun.hit.edu.cn or bliu@gordonlifescience.org Supplementary information: Supplementary data are available at Bioinformatics online. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537947/ doi: 10.1093/bioinformatics/btt709 id: cord-350309-j4oh1z8m author: Liu, D. X. title: Coronavirus envelope protein: A small membrane protein with multiple functions date: 2007-05-29 words: 3403.0 sentences: 167.0 pages: flesch: 48.0 cache: ./cache/cord-350309-j4oh1z8m.txt txt: ./txt/cord-350309-j4oh1z8m.txt summary: The E proteins from infectious bronchitis virus (IBV) and mouse hepatitis virus (MHV) are translated from the third and second ORFs of mRNA 3 and 5 of the respective viruses by a cap-independent, internal ribosomal entry mechanism [6] [7] [8] [9] [10] [11] [12] . This modification is unique to SARS-CoV E protein, and it is still unknown whether the modification can also be detected in virus-infected cells and in virions. However, the membrane topologies of SARS-CoV E protein in virions and in virusinfected cells are still unknown. Similar to other viroporins [46] , expression of SARS-CoV and MHV E protein enhanced the membrane permeability of bacterial and mammalian cells [47, 48] . These results indicate that the ion channel activity of coronavirus E protein is important for virus replication, especially in the case of some coronaviruses, such as MHV. Biochemical evidence for the presence of mixed membrane topologies of the severe acute respiratory syndrome coronavirus envelope protein expressed in mammalian cells abstract: Coronavirus envelope protein is a small membrane protein and minor component of the virus particles. It plays important roles in virion assembly and morphogenesis, alteration of the membrane permeability of host cells and virus-host cell interaction. Here we review recent progress in characterization of the biochemical properties, membrane topology and functions of the protein. url: https://www.ncbi.nlm.nih.gov/pubmed/17530462/ doi: 10.1007/s00018-007-7103-1 id: cord-316745-n10ia3j3 author: Liu, HongDe title: A new approach to the prediction of transmembrane structures date: 2008-05-23 words: 1828.0 sentences: 133.0 pages: flesch: 61.0 cache: ./cache/cord-316745-n10ia3j3.txt txt: ./txt/cord-316745-n10ia3j3.txt summary: In this paper, a new approach, maximum spectrum of continuous wavelet transform (MSCWT), is proposed to predict TMHs. The predictions for eight SARS-CoV membrane proteins indicate that MSCWT has the same capacity with software TMpred. In this paper, MSCWT was proposed to predict TMHs of membrane proteins. MSCWT of a signal could be obtained from the following steps: firstly, choose an appreciated mother wavelet and an appreciated scale range to perform CWT; then, detect and record the CWT maximum at every translation; finally, plot the recorded maximum value to its position (translation). Figure 1 shows the TMHs predicted by MSCWT and TMpred for SARS-CoV protein Orf9 and Orf14. MSCWT has the highest accuracy rate of membrane protein sequence (84.6%), while TMpred and DAS are 75.4% and 80.0%, respectively. In this paper, the proposed new method MSCWT shows a good efficiency in predicting the positions and amounts of TMHs of membrane protein. abstract: About 20%–30% of genome products have been predicted as membrane proteins, which have significant biological functions. The prediction of the amount and position for the transmembrane protein helical segments (TMHs) is the hot spot in bioinformatics. In this paper, a new approach, maximum spectrum of continuous wavelet transform (MSCWT), is proposed to predict TMHs. The predictions for eight SARS-CoV membrane proteins indicate that MSCWT has the same capacity with software TMpred. Moreover, the test on a dataset of 131 structure-known proteins with 548 TMHs shows that the prediction accuracy of MSCWT for TMHs is 91.6% and that for membrane protein is 89.3%. url: https://doi.org/10.1007/s11434-008-0055-5 doi: 10.1007/s11434-008-0055-5 id: cord-346965-0oq2n0af author: Liu, Zhi-Ping title: Bridging protein local structures and protein functions date: 2008-04-18 words: 14491.0 sentences: 810.0 pages: flesch: 44.0 cache: ./cache/cord-346965-0oq2n0af.txt txt: ./txt/cord-346965-0oq2n0af.txt summary: The characteristics between interface and noninterface portions of a protein surface, such as sequence conservation, proportions of amino acids, secondary structure, solvent accessibility and side-chain conformational entropy, are often used to distinguish the specificity of local structures relating to protein binding function. The method relies on a simplified representation of the chemical groups found in amino acid side-chains to identify functional sites from a single protein structure and a number of its sequence homologs. (2006) improved previous approaches by combining two known measures of ''functionality'' in proteins, i.e. cleft volume and residue conservation, to develop a method for identifying the location of ligand-binding pockets in proteins. (2006) applied an SVM method to predict DNA-binding sites using the features including amino acid sequence, profile of evolutionary conservation of sequence positions, and low-resolution structural information. (2006) developed a method to predict both protein-protein binding site location and interface type (obligate or non-obligate) using a Bayesian network in combination with surface patch analysis. abstract: One of the major goals of molecular and evolutionary biology is to understand the functions of proteins by extracting functional information from protein sequences, structures and interactions. In this review, we summarize the repertoire of methods currently being applied and report recent progress in the field of in silico annotation of protein function based on the accumulation of vast amounts of sequence and structure data. In particular, we emphasize the newly developed structure-based methods, which are able to identify locally structural motifs and reveal their relationship with protein functions. These methods include computational tools to identify the structural motifs and reveal the strong relationship between these pre-computed local structures and protein functions. We also discuss remaining problems and possible directions for this exciting and challenging area. url: https://www.ncbi.nlm.nih.gov/pubmed/18421562/ doi: 10.1007/s00726-008-0088-8 id: cord-305602-yzc4bosn author: Llano, Manuel title: Chapter Seven Defining Pharmacological Targets by Analysis of Virus–Host Protein Interactions date: 2018-12-31 words: 5909.0 sentences: 324.0 pages: flesch: 41.0 cache: ./cache/cord-305602-yzc4bosn.txt txt: ./txt/cord-305602-yzc4bosn.txt summary: This higher than expected connectivity suggests that the direct interactions of viral proteins with host factors allow the access of the virus to cellular complexes. For example, in a TAP-MS experiment were mapped 3787 complex associations between 54 viral proteins from different viruses and 1079 host proteins (Rozenblatt-Rosen et al., 2012) , highlighting the high degree of connectivity of the interacting proteins. As discussed above, some of the host factors predicted, by the combined transcriptional profiling and in silico analyses, to interact with host proteins implicated in direct binary contacts with influenza proteins (Y2H interactors) were demonstrated to influence viral replication in functional screenings (Shapira et al., 2009 ). Most of the small molecules interfering with PPIs bind directly to the implicated surfaces of interactions (orthosteric modulators) by targeting hot spot residues or by molecular mimicry of elements of secondary structures (Arkin et al., 2014; Basse et al., 2016; Fry, 2006; Wells & McClendon, 2007; Yin & Hamilton, 2005) . abstract: Abstract Viruses are obligate parasites that depend on cellular factors for replication. Pharmacological inhibition of essential viral proteins, mostly enzymes, is an effective therapeutic alternative in the absence of effective vaccines. However, this strategy commonly encounters drug resistance mechanisms that allow these pathogens to evade control. Due to the dependency on host factors for viral replication, pharmacological disruption of the host-pathogen protein–protein interactions (PPIs) is an important therapeutic alternative to block viral replication. In this review we discuss salient aspects of PPIs implicated in viral replication and advances in the development of small molecules that inhibit viral replication through antagonism of these interactions. url: https://www.ncbi.nlm.nih.gov/pubmed/29459033/ doi: 10.1016/bs.apcsb.2017.11.001 id: cord-017775-qohf9pxp author: Loa, Chien Chang title: Recombinant Turkey Coronavirus Nucleocapsid Protein Expressed in Escherichia coli date: 2015-09-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Expression and purification of turkey coronavirus (TCoV) nucleocapsid (N) protein from a prokaryotic expression system as histidine-tagged fusion protein are presented in this chapter. Expression of histidine-tagged fusion N protein with a molecular mass of 57 kDa is induced with isopropyl β-d-1-thiogalactopyranoside (IPTG). The expressed N protein inclusion body is extracted and purified by chromatography on nickel-agarose column to near homogeneity. The protein recovery can be 10 mg from 100 ml of bacterial culture. The purified N protein is a superior source of TCoV antigen for antibody-capture ELISA for detection of antibodies to TCoV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122433/ doi: 10.1007/978-1-4939-3414-0_4 id: cord-290088-g9559ux3 author: Loh, Hwei-San title: Using transgenic plants and modified plant viruses for the development of treatments for human diseases date: 2017-08-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Production of proteins in plants for human health applications has become an attractive strategy attributed by their potentials for low-cost production, increased safety due to the lack of human or animal pathogens, scalability and ability to produce complex proteins. A major milestone for plant-based protein production for use in human health was achieved when Protalix BioTherapeutics produced taliglucerase alfa (Elelyso(®)) in suspension cultures of a transgenic carrot cell line for the treatment of patients with Gaucher's disease, was approved by the USA Food and Drug Administration in 2012. In this review, we are highlighting various approaches for plant-based production of proteins and recent progress in the development of plant-made therapeutics and biologics for the prevention and treatment of human diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/28800551/ doi: 10.1016/j.coviro.2017.07.019 id: cord-262904-0b0ljjq1 author: Lon, Jerome Rumdon title: Prediction and evolution of B cell epitopes of surface protein in SARS-CoV-2 date: 2020-10-29 words: 5006.0 sentences: 263.0 pages: flesch: 53.0 cache: ./cache/cord-262904-0b0ljjq1.txt txt: ./txt/cord-262904-0b0ljjq1.txt summary: It is worth mentioning that all 6 identified epitopes were conserved in nearly 3500 SARS-CoV-2 genomes, showing that it is helpful to obtain stable and long-acting epitopes under the condition of high frequency of amino acid mutation, which deserved further study at the experiment level. On this basis, we predicted the linear and conformational B cell epitopes, analyzed the conservation of the epitopes, the adaptability and other evolutionary characteristics of the surface protein, which provided a theoretical basis for the vaccine development and prevention of SARS-CoV-2. With the amino acid sequences of the surface protein of SARS-CoV-2 of NC_045512.2 as templates, we predicted the 3D structure of E and M protein through the online server SWISS-MODEL [10] based on homology modeling method, selected the optimal structure based on the template identity and GMQE value [10] , and the rationality of the structure was evaluated by Ramachandran plot [11] with PDBsum server. abstract: BACKGROUND: In order to obtain antibodies that recognize natural proteins, it is possible to predict the antigenic determinants of natural proteins, which are eventually embodied as polypeptides. The polypeptides can be coupled with corresponding vectors to stimulate the immune system to produce corresponding antibodies, which is also a simple and effective vaccine development method. The discovery of epitopes is helpful to the development of SARS-CoV-2 vaccine. METHODS: The analyses were related to epitopes on 3 proteins, including spike (S), envelope (E) and membrane (M) proteins, which are located on the lipid envelope of the SARS-CoV-2. Based on the NCBI Reference Sequence: NC_045512.2, the conformational and linear B cell epitopes of the surface protein were predicted separately by various prediction methods. Furthermore, the conservation of the epitopes, the adaptability and other evolutionary characteristics were also analyzed, the sequences of the whole genome of SARS-CoV-2 were obtained from the GISAID. RESULTS: 7 epitopes were predicted, including 6 linear epitopes and 1 conformational epitope. One of the linear and one of the conformational consist of identical sequence, but represent different forms of epitopes. It is worth mentioning that all 6 identified epitopes were conserved in nearly 3500 SARS-CoV-2 genomes, showing that it is helpful to obtain stable and long-acting epitopes under the condition of high frequency of amino acid mutation, which deserved further study at the experiment level. CONCLUSION: The findings would facilitate the vaccine development, had the potential to be directly applied on the prevention in this disease, but also have the potential to prevent the possible threats caused by other types of coronavirus. url: https://doi.org/10.1186/s12985-020-01437-4 doi: 10.1186/s12985-020-01437-4 id: cord-296347-fanlvxqs author: Loureiro, Joana title: Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions date: 2006-12-02 words: 28921.0 sentences: 1425.0 pages: flesch: 45.0 cache: ./cache/cord-296347-fanlvxqs.txt txt: ./txt/cord-296347-fanlvxqs.txt summary: We discuss the many human cytomegalovirus (HCMV)-encoded immunomodulatory genes that interfere with antigen presentation (immunoevasins) and focus on the HCMV immunoevasins US2 and US11, which induce the degradation of class I MHC heavy chains by the proteasome by catalyzing their export from the endoplasmic reticulum (ER)-membrane into the cytosol, a process termed ER dislocation. One theme that arises from the characterization of this process over the 10 years that have passed since its discovery is that HC dislocation is unique in many respects: HC molecules do not meet the requirement of being either misfolded or misassembled, yet their dislocation takes place by virtue of the presence of US2 or US11; the speed of HC degradation is unrivaled by that of any other ER-associated degradation substrates: HC half-life is reduced from hours to a mere 2-5 min in cells infected by HCMV or in ce lls expressin g either US2 or US11 ( Wiertz et al ., 1996a ,b) ; both US2 and US11 have stringent requirements in terms of which HLA alleles (Barel et al., 2003 (Barel et al., , 2006 Machold et al., 1997) or assembly, folding and ubiquitination status of the class I MHC complex (Blom et al., 2004; Furman et al., 2003; Gewurz et al., 2001) either viral protein is able to target for dislocation and proteasomal destruction. abstract: Relatively small genomes and high replication rates allow viruses and bacteria to accumulate mutations. This continuously presents the host immune system with new challenges. On the other side of the trenches, an increasingly well‐adjusted host immune response, shaped by coevolutionary history, makes a pathogen's life a rather complicated endeavor. It is, therefore, no surprise that pathogens either escape detection or modulate the host immune response, often by redirecting normal cellular pathways to their advantage. For the purpose of this chapter, we focus mainly on the manipulation of the class I and class II major histocompatibility complex (MHC) antigen presentation pathways and the ubiquitin (Ub)‐proteasome system by both viral and bacterial pathogens. First, we describe the general features of antigen presentation pathways and the Ub‐proteasome system and then address how they are manipulated by pathogens. We discuss the many human cytomegalovirus (HCMV)‐encoded immunomodulatory genes that interfere with antigen presentation (immunoevasins) and focus on the HCMV immunoevasins US2 and US11, which induce the degradation of class I MHC heavy chains by the proteasome by catalyzing their export from the endoplasmic reticulum (ER)‐membrane into the cytosol, a process termed ER dislocation. US2‐ and US11‐mediated subversion of ER dislocation ensures proteasomal degradation of class I MHC molecules and presumably allows HCMV to avoid recognition by cytotoxic T cells, whilst providing insight into general aspects of ER‐associated degradation (ERAD) which is used by eukaryotic cells to purge their ER of defective proteins. We discuss the similarities and differences between the distinct pathways co‐opted by US2 and US11 for dislocation and degradation of human class I MHC molecules and also a putatively distinct pathway utilized by the murine herpes virus (MHV)‐68 mK3 immunoevasin for ER dislocation of murine class I MHC. We speculate on the implications of the three pathogen‐exploited dislocation pathways to cellular ER quality control. Moreover, we discuss the ubiquitin (Ub)‐proteasome system and its position at the core of antigen presentation as proteolysis and intracellular trafficking rely heavily on Ub‐dependent processes. We add a few examples of manipulation of the Ub‐proteasome system by pathogens in the context of the immune system and such diverse aspects of the host–pathogen relationship as virus budding, bacterial chromosome integration, and programmed cell death, to name a few. Finally, we speculate on newly found pathogen‐encoded deubiquitinating enzymes (DUBs) and their putative roles in modulation of host–pathogen interactions. url: https://api.elsevier.com/content/article/pii/S0065277606920069 doi: 10.1016/s0065-2776(06)92006-9 id: cord-196265-mvnkkcow author: M''esz''aros, B''alint title: Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications date: 2020-04-21 words: 12653.0 sentences: 666.0 pages: flesch: 47.0 cache: ./cache/cord-196265-mvnkkcow.txt txt: ./txt/cord-196265-mvnkkcow.txt summary: We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif resource, ELM, and were presented with candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton and cell signalling. Proximity-based mass spectrometry on the MHV replication complex further revealed that the RTC environment repurposes components from the host autophagy, vesicular trafficking and translation machineries (V''kovski et al., 2019) In the present work, we identify a set of conserved SLiM candidates in the ACE2 and integrin proteins, which are likely to act in the cell entry system of SARS-CoV-2. The C-terminal tail of both subunits share a high degree of sequence similarity, and similarly to ACE2, contain several known and candidate SLiMs (see Table 1 and Figure 6 ) that propagate signals in the cytoplasm and regulate integrin activity not just through intracellular pathways, but also changing the structural state of the ectodomains determining ligand binding capacity (Anthis and Campbell, 2011) . abstract: The primary cell surface receptor for SARS-CoV-2 is the angiotensin-converting enzyme 2 (ACE2). Recently it has been noticed that the viral Spike protein has an RGD motif, suggesting that cell surface integrins may be co-receptors. We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif resource, ELM, and were presented with candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton and cell signalling. These SLiM candidates are highly conserved in vertebrates. They suggest potential interactions with the AP2 mu2 subunit as well as I-BAR, LC3, PDZ, PTB and SH2 domains found in signalling and regulatory proteins present in epithelial lung cells. Several motifs overlap in the tail sequences, suggesting that they may act as molecular switches, often involving tyrosine phosphorylation status. Candidate LIR motifs are present in the tails of ACE2 and integrin beta3, suggesting that these proteins can directly recruit autophagy components. We also noticed that the extracellular part of ACE2 has a conserved MIDAS structural motif, which are commonly used by beta integrins for ligand binding, potentially supporting the proposal that integrins and ACE2 share common ligands. The findings presented here identify several molecular links and testable hypotheses that might help uncover the mechanisms of SARS-CoV-2 attachment, entry and replication, and strengthen the possibility that it might be possible to develop host-directed therapies to dampen the efficiency of viral entry and hamper disease progression. The strong sequence conservation means that these putative SLiMs are good candidates: Nevertheless, SLiMs must always be validated by experimentation before they can be stated to be functional. url: https://arxiv.org/pdf/2004.10274v1.pdf doi: nan id: cord-004400-li1sc47z author: Ma, Jingjiao title: Acetylation at K108 of the NS1 protein is important for the replication and virulence of influenza virus date: 2020-02-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Non-structural protein 1 (NS1) of influenza virus is a multifunctional protein that plays an important role in virus replication and virulence. In this study, an acetylation modification was identified at the K108 residue of the NS1 protein of H1N1 influenza virus. To further explore the function of the K108 acetylation modification of the NS1 protein, a deacetylation-mimic mutation (K108R) and a constant acetylation-mimic mutation (K108Q) were introduced into the NS1 protein in the background of A/WSN/1933 H1N1 (WSN), resulting in two mutant viruses (WSN-NS1-108R and WSN-NS1-108Q). In vitro and mouse studies showed that the deacetylation-mimic mutation K108R in the NS1 protein attenuated the replication and virulence of WSN-NS1-108R, while the constant acetylation-mimic mutant virus WSN-NS1-108Q showed similar replication and pathogenicity as the wild-type WSN virus (WSN-wt). The results indicated that acetylation at K108 of the NS1 protein has an important role in the replication and virulence of influenza virus. To further explore the potential mechanism, the type I interferon (IFN-I) antagonistic activity of the three NS1 proteins (NS1-108Q, NS1-108R, and NS1-wt) was compared in cells, which showed that the K108R mutation significantly attenuated the IFN-β antagonistic activity of the NS1 protein compared with NS1-wt and NS1-108Q. Both NS1-wt and NS1-108Q inhibited the IFN-β response activated by RIG-I CARD domain, MAVS, TBK1, and IRF3 more efficiently than the NS1-108R protein in cells. Taken together, the results indicated that acetylation at NS1 K108 is important for the IFN antagonistic activity of the NS1 protein and virulence of the influenza virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038556/ doi: 10.1186/s13567-020-00747-3 id: cord-337067-j8ebslif author: Mades, Andreas title: Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins date: 2012-11-15 words: 8726.0 sentences: 459.0 pages: flesch: 48.0 cache: ./cache/cord-337067-j8ebslif.txt txt: ./txt/cord-337067-j8ebslif.txt summary: The overexpression of Sec63 reduces the steady-state levels of viral and cellular multi-spanning membrane proteins in a cotranslational mode, while soluble and single-spanning ER reporters are not affected. The specific action of Sec63 is further sustained by our observations that the up-regulation of either Sec62 or two other ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the steady-state level of a multi-spanning membrane reporter. Similar results were obtained with cell lysates prepared with the denaturing detergent SDS (Fig. 1B) , indicating that the observed down-regulation of HBV.S by excess Sec63 was not merely due to changes in the solubility profile. To analyze whether an up-regulation of these ERdj proteins might also affect the level of a multi-spanning membrane protein, FLAG-tagged versions of ERdj1 and ERdj4 were cotransfected with HBV.S. FLAG-specific Western blotting confirmed the ectopic expression of ERdj1 and ERdj4 in 63 and 25 kDa forms, respectively, consistent with their theoretical molecular masses (Fig. 9) . abstract: The Sec61 translocon of the endoplasmic reticulum (ER) membrane forms an aqueous pore, allowing polypeptides to be transferred across or integrated into membranes. Protein translocation into the ER can occur co- and posttranslationally. In yeast, posttranslational translocation involves the heptameric translocase complex including its Sec62p and Sec63p subunits. The mammalian ER membrane contains orthologs of yeast Sec62p and Sec63p, but their function is poorly understood. Here, we analyzed the effects of excess and deficit Sec63 on various ER cargoes using human cell culture systems. The overexpression of Sec63 reduces the steady-state levels of viral and cellular multi-spanning membrane proteins in a cotranslational mode, while soluble and single-spanning ER reporters are not affected. Consistent with this, the knock-down of Sec63 increases the steady-state pools of polytopic ER proteins, suggesting a substrate-specific and regulatory function of Sec63 in ER import. Overexpressed Sec63 exerts its down-regulating activity on polytopic protein levels independent of its Sec62-interacting motif, indicating that it may not act in conjunction with Sec62 in human cells. The specific action of Sec63 is further sustained by our observations that the up-regulation of either Sec62 or two other ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the steady-state level of a multi-spanning membrane reporter. A J domain-specific mutation of Sec63, proposed to weaken its interaction with the ER resident BiP chaperone, reduces the down-regulating capacity of excess Sec63, suggesting an involvement of BiP in this process. Together, these results suggest that Sec63 may perform a substrate-selective quantity control function during cotranslational ER import. url: https://doi.org/10.1371/journal.pone.0049243 doi: 10.1371/journal.pone.0049243 id: cord-356019-k7gs1ohp author: Makhzoum, Abdullah title: Recent advances on host plants and expression cassettes'' structure and function in plant molecular pharming date: 2013-08-20 words: 8923.0 sentences: 405.0 pages: flesch: 40.0 cache: ./cache/cord-356019-k7gs1ohp.txt txt: ./txt/cord-356019-k7gs1ohp.txt summary: As molecular pharming platforms, plants are excellent biofactories for the production of drugs, antibodies, and vaccines in various host systems such as whole transgenic plants, cell suspension culture, hairy roots, and hydroponic culture [1] [2] [3] . Here, we review these aspects and report recent advances in the improvements of plant molecular pharming to increase protein yield and accumulation based on upstream and downstream processing studies and empirical essays. In addition to the importance of promoter architecture for gene expression in molecular pharming, other strategies based on using specific peptides at N-and C-termini have been employed to enhance the transcript level of recombinant proteins. For example, the production and accumulation of the recombinant human granulocyte colony-stimulating factor was significantly increased in transgenic rice suspension culture by an RNAi approach designed to suppress the cysteine proteinase gene expression or by the inhibition of proteinase [104, 105] . abstract: Plant molecular pharming is a promising system to produce important recombinant proteins such as therapeutic antibodies, pharmaceuticals, enzymes, growth factors, and vaccines. The system provides an interesting alternative method to the direct extraction of proteins from inappropriate source material while offering the possibility to overcome problems related to product safety and source availability. Multiple factors including plant hosts, genes of interest, expression vector cassettes, and extraction and purification techniques play important roles in the plant molecular pharming. Plant species, as a biosynthesis platform, are a crucial factor in achieving high yields of recombinant protein in plant. The choice of recombinant gene and its expression strategy is also of great importance in ensuring a high amount of the recombinant proteins. Many studies have been conducted to improve expression, accumulation, and purification of the recombinant protein from molecular pharming systems. Re-engineered vectors and expression cassettes are also pivotal tools in enhancing gene expression at the transcription and translation level, and increasing protein accumulation, stability, retention and targeting of specific organelles. In this review, we report recent advances and strategies of plant molecular pharming while focusing on the choice of plant hosts and the role of some molecular pharming elements and approaches: promoters, codon optimization, signal sequences, and peptides used for upstream design, purification and downstream processing. url: https://doi.org/10.1007/s40259-013-0062-1 doi: 10.1007/s40259-013-0062-1 id: cord-022499-7d58f1k3 author: Mall, Sanjay title: Transmembrane α helices date: 2004-01-07 words: 12212.0 sentences: 583.0 pages: flesch: 55.0 cache: ./cache/cord-022499-7d58f1k3.txt txt: ./txt/cord-022499-7d58f1k3.txt summary: For example, if effects were averaged over three shells of lipids, changes in fatty acyl chain lengths by 4 and 10 carbons from that giving optimal interaction would decrease lipid-protein binding constants by factors of 1.6 and 21, respectively. These results suggest that the effects of charge on the interactions between phospholipids and transmembrane ot helices will often be rather small and will be strongly dependent on the detailed structure of the peptide and its orientation in the membrane. However, there is evidence for the presence of a small number of "special" anionic phospholipids binding to some membrane proteins, acting as "cofactors." An example is provided by cytochrome c oxidase, whose crystal structure shows the presence of a lipid molecule bound between the transmembrane a helices (Iwata et al., 1995) . It could therefore be that matching of the thickness of the lipid bilayer and the transmembrane length of the protein is important in retention in ER, as was suggested for the Golgi complex. abstract: This chapter discusses effects of intrinsic membrane proteins on lipid bilayers and model transmembrane α helices. Incorporation of a protein into a lipid bilayer has significant effects on the properties of the bilayer. The rough surface presented by a protein to the surrounding lipid bilayer tends to produce poor packing unless the lipid fatty acyl chains distort to match the surface of the protein. In a liquid crystalline bilayer the lipid fatty acyl chains are disordered, because the chains undergo extensive wobbling fluctuations. The presence of a rigid protein surface reduces the extent of these motional fluctuations. However, the chains tilt and become conformationally disordered to maximize contact with the rough surface of the protein. The net result is that the presence of a protein leads to decreased order for the chains, with a wide range of chain orientations relative to the bilayer normal, but with reduced extent and rate of motion. Because of the reduced motion, lipids adjacent to membrane proteins are often referred to as being motionally restricted. It is clear that the reasons for the disorder of the bulk lipids and the disorder of the lipids adjacent to the protein are different; for the bulk phospholipids, the disorder is dynamic, whereas, for the boundary lipids the disorder is static. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157917/ doi: 10.1016/s1063-5823(02)52014-7 id: cord-286970-4pl95r0o author: Mamipour, Mina title: An overview on molecular chaperones enhancing solubility of expressed recombinant proteins with correct folding date: 2017-04-12 words: 4994.0 sentences: 279.0 pages: flesch: 50.0 cache: ./cache/cord-286970-4pl95r0o.txt txt: ./txt/cord-286970-4pl95r0o.txt summary: In this article, we attempted to review cytoplasmic chaperones such as Hsp families and periplasmic chaperones including; generic chaperones, specialized chaperones, PPIases, and proteins involved in disulfide bond formation. Numerous studies demonstrate positive effects of molecular chaperons on correct folding formation of recombinant protein and prevention of IBs formation in the cytoplasm and periplasm [17, 18] . In this review we focused on cytoplasmic and periplasmic chaperones category and their applications in recombinant protein expression with correct folding. The Hsp90 family are highly conserved and proteins, which exist in all organisms from bacteria to humans and their expressions rises in response to the stress conditions in prokaryotic and eukaryotic LolA (B,C,D,E) periplasm space, Inner membrane and Outer membrane rapid transfer of associated lipoproteins ATP (+) [108] PapD and its family periplasm space and Outer membrane biogenesis of pilus (−) [163] FimC periplasm space interacts with each pilus subunit (−) [164] cells. abstract: The majority of research topics declared that most of the recombinant proteins have been expressed by Escherichia coli in basic investigations. But the majority of high expressed proteins formed as inactive recombinant proteins that are called inclusion body. To overcome this problem, several methods have been used including suitable promoter, environmental factors, ladder tag to secretion of proteins into the periplasm, gene protein optimization, chemical chaperones and molecular chaperones sets. Co-expression of the interest protein with molecular chaperones is one of the common methods The chaperones are a group of proteins, which are involved in making correct folding of recombinant proteins. Chaperones are divided two groups including; cytoplasmic and periplasmic chaperones. Moreover, periplasmic chaperones and proteases can be manipulated to increase the yields of secreted proteins. In this article, we attempted to review cytoplasmic chaperones such as Hsp families and periplasmic chaperones including; generic chaperones, specialized chaperones, PPIases, and proteins involved in disulfide bond formation. url: https://api.elsevier.com/content/article/pii/S0141813017304944 doi: 10.1016/j.ijbiomac.2017.04.025 id: cord-001866-s5otdtwq author: Mandal, Nakul title: Proteomic Analysis of the Vitreous following Experimental Retinal Detachment in Rabbits date: 2015-11-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Purpose. The pathogenesis of rhegmatogenous retinal detachment (RRD) remains incompletely understood, with no clinically effective treatment for potentially severe complications such as photoreceptor cell death and proliferative vitreoretinopathy. Here we investigate the protein profile of the vitreous following experimental retinal detachment using a comparative proteomic based approach. Materials and Methods. Retinal detachment was created in the right eyes of six New Zealand red pigmented rabbits. Sham surgery was undertaken in five other rabbits that were used as controls. After seven days the eyes were enucleated and the vitreous was removed. The vitreous samples were evaluated with two-dimensional polyacrylamide gel electrophoresis and the differentially expressed proteins were identified with tandem mass spectrometry. Results. Ten protein spots were found to be at least twofold differentially expressed when comparing the vitreous samples of the sham and retinal detachment surgery groups. Protein spots that were upregulated in the vitreous following retinal detachment were identified as albumin fragments, and those downregulated were found to be peroxiredoxin 2, collagen-Iα1 fragment, and α-1-antiproteinase F. Conclusions. Proteomic investigation of the rabbit vitreous has identified a set of proteins that help further our understanding of the pathogenesis of rhegmatogenous retinal detachment and its complications. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667062/ doi: 10.1155/2015/583040 id: cord-259112-tkj5de7b author: Mandal, Santi M title: Inhaler with electrostatic sterilizer and use of cationic amphiphilic peptides may accelerate recovery from COVID-19 date: 2020-06-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We explore the design of a smart inhaler with electrostatic sterilizer and propose the utilization of cationic amphiphilic peptides, independently or in conjunction with a bronchodilator, for COVID-19 patients to quickly improve wellbeing while maintaining a strategic distance to protect healthcare personnel from virus-containing aerosol or droplets during the process of inhalation. url: https://doi.org/10.2144/btn-2020-0042 doi: 10.2144/btn-2020-0042 id: cord-280679-jj3wzojy author: Marblestone, Jeffrey G. title: Comparison of SUMO fusion technology with traditional gene fusion systems: Enhanced expression and solubility with SUMO date: 2006-01-01 words: 4854.0 sentences: 250.0 pages: flesch: 54.0 cache: ./cache/cord-280679-jj3wzojy.txt txt: ./txt/cord-280679-jj3wzojy.txt summary: For this study, three model proteins, enhanced green florescent protein (eGFP), matrix metalloprotease-13 (MMP13), and myostatin (growth differentiating factor-8, GDF8), were fused to the C termini of maltose-binding protein (MBP), glutathione S-transferase (GST), thioredoxin (TRX), NUS A, ubiquitin (Ub), and SUMO tags. Taken together, these results demonstrate that SUMO is superior to commonly used fusion tags in enhancing expression and solubility with the distinction of generating recombinant protein with native sequences. Three candidate proteins, enhanced green fluorescent protein (eGFP), and two previously described difficult-to-express proteins, matrix metalloprotease-13 (MMP13) and myostatin (growth differentiating factor-8, GDF8), were expressed as fusions with maltose-binding protein (MBP), glutathione S-transferase (GST), thioredoxin (TRX), NUS A, ubiquitin (Ub), and SUMO. The ability of commonly used fusion tags to enhance protein expression and solubility was investigated using three candidate proteins (eGFP, MMP13, and GDF8) and six fusion tags (SUMO, Ub, MBP, GST, TRX, and NUS A). abstract: Despite the availability of numerous gene fusion systems, recombinant protein expression in Escherichia coli remains difficult. Establishing the best fusion partner for difficult-to-express proteins remains empirical. To determine which fusion tags are best suited for difficult-to-express proteins, a comparative analysis of the newly described SUMO fusion system with a variety of commonly used fusion systems was completed. For this study, three model proteins, enhanced green florescent protein (eGFP), matrix metalloprotease-13 (MMP13), and myostatin (growth differentiating factor-8, GDF8), were fused to the C termini of maltose-binding protein (MBP), glutathione S-transferase (GST), thioredoxin (TRX), NUS A, ubiquitin (Ub), and SUMO tags. These constructswere expressed in E. coli and evaluated for expression and solubility. As expected, the fusion tags varied in their ability to produce tractable quantities of soluble eGFP, MMP13, and GDF8. SUMO and NUS A fusions enhanced expression and solubility of recombinant proteins most dramatically. The ease at which SUMO and NUS A fusion tags were removed from their partner proteins was then determined. SUMO fusions are cleaved by the natural SUMO protease, while an AcTEV protease site had to be engineered between NUS A and its partner protein. A kinetic analysis showed that the SUMO and AcTEV proteases had similarK(M) values, but SUMOprotease had a 25-fold higher k(cat) than AcTEV protease, indicating a more catalytically efficient enzyme. Taken together, these results demonstrate that SUMO is superior to commonly used fusion tags in enhancing expression and solubility with the distinction of generating recombinant protein with native sequences. url: https://www.ncbi.nlm.nih.gov/pubmed/16322573/ doi: 10.1110/ps.051812706 id: cord-258468-52gej3co author: Marcekova, Zuzana title: Heterologous expression of full-length capsid protein of porcine circovirus 2 in Escherichia coli and its potential use for detection of antibodies date: 2009-08-05 words: 6991.0 sentences: 326.0 pages: flesch: 53.0 cache: ./cache/cord-258468-52gej3co.txt txt: ./txt/cord-258468-52gej3co.txt summary: title: Heterologous expression of full-length capsid protein of porcine circovirus 2 in Escherichia coli and its potential use for detection of antibodies coli-expressed Cap protein to self-assemble into virus-like particles (VLPs), the immunization of mice with recombinant Cap yielded antibodies with the same specificity as those raised against native PCV 2 virions. In addition, the antigenic properties of the purified Cap protein were employed in a subunit-based indirect ELISA to monitor the levels of PCV 2 specific antibodies in piglets originating from a herd which was experiencing PCV 2 infection. In order to eliminate the cluster of rare codons from the 5 end of the cap gene, the expression vector encoding a truncated variant of Cap protein ( Cap-His), which was lacking the first 16 amino acid residues, was constructed (Fig. 1B) . In summary, a bacterial expression system has been developed for the production of the full-length recombinant capsid protein of porcine circovirus type 2. abstract: A capsid protein of porcine circovirus 2 (PCV 2) serves as a diagnostic antigen for the detection of PCV 2-associated disease known as a postweaning multisystemic wasting syndrome (PMWS). In this report, a bacterial expression system was developed for the expression and purification of the full-length PCV 2 capsid (Cap) protein from a codon-optimized cap gene. Replacement of rare arginine codons located at the 5′ end of the cap reading frame with codons optimal for E. coli was found to overcome the poor expression of the viral protein in the prokaryotic system. The Cap protein was purified to greater than 95% homogeneity by using a single cation-exchange chromatography at a yield of 10 mg per litre of bacterial culture. Despite the failure of the E. coli-expressed Cap protein to self-assemble into virus-like particles (VLPs), the immunization of mice with recombinant Cap yielded antibodies with the same specificity as those raised against native PCV 2 virions. In addition, the antigenic properties of the purified Cap protein were employed in a subunit-based indirect ELISA to monitor the levels of PCV 2 specific antibodies in piglets originating from a herd which was experiencing PCV 2 infection. These results pave the way for a straightforward large-scale production of the recombinant PCV 2 capsid protein and its use as a diagnostic antigen or a PCV 2 subunit vaccine. url: https://api.elsevier.com/content/article/pii/S0166093409003541 doi: 10.1016/j.jviromet.2009.07.028 id: cord-005145-1l87fdmi author: Marquet-Blouin, E. title: Neutralizing immunogenicity of transgenic carrot (Daucus carota L.)-derived measles virus hemagglutinin date: 2003 words: 5640.0 sentences: 282.0 pages: flesch: 49.0 cache: ./cache/cord-005145-1l87fdmi.txt txt: ./txt/cord-005145-1l87fdmi.txt summary: Despite differences in post-translational processing viral and bacterial antigens preserved their immunogenic properties when produced in plants and induced cross-reactive and sometimes neutralizing and protective antibodies. The aim of this study was (1) to explore the potential of carrots as an expression system for antigens that is suitable for human consumption, and (2) to test whether the measles virus hemagglutinin glycoprotein would preserve its neutralizing immunogenicity in this system. Although some work has been done with transgenic carrot callus cells (Brodzik et al., 2000) , this is one of the first reports of the expression of a transgenic antigen in mature carrots, showing that high levels of virus-neutralizing antibodies can be induced with a glycoprotein produced in this plant. The flow cytometry data showed that all mice vaccinated with transgenic leaf or root extracts produced high levels of antibodies cross-reacting with the native protein independently whether virus-infected or H-protein transfected cells were used. Plant-derived measles virus hemagglutinin protein induces neutralizing antibodies in mice abstract: Although edible vaccines seem to be feasible, antigens of human pathogens have mostly been expressed in plants that are not attractive for human consumption (such as potatoes) unless they are cooked. Boiling may reduce the immunogenicity of many antigens. More recently, the technology to transform fruit and vegetable plants have become perfected. We transformed carrot plants with Agrobacterium tumefaciens to generate plants (which can be eaten raw) transgenic for an immunodominant antigen of the measles virus, a major pathogen in man. The hemagglutinin (H) glycoprotein is the principle target of neutralizing and protective antibodies against measles. Copy numbers of the H transgene were verified by Southern blot and specific transcription was confirmed by RT-PCR. The H protein was detected by western blot in the membrane fraction of transformed carrot plants. The recombinant protein seemed to have a 8% lower molecular weight than the viral protein. Although this suggests a different glycosylation pattern, proper folding of the transgenic protein was confirmed by conformational-dependent monoclonal antibodies. Immunization of mice with leaf or root extracts induced high titres of IgG1 and IgG2a antibodies that cross-reacted strongly with the measles virus and neutralized the virus in vitro. These results demonstrate that transgenic carrot plants can be used as an efficient expression system to produce highly immunogenic viral antigens. Our study may pave the way towards an edible vaccine against measles which could be complementary to the current live-attenuated vaccine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088612/ doi: 10.1023/a:1022354322226 id: cord-307227-x6xketcn author: Martin, William R. title: Repurposing of FDA-Approved Toremifene to Treat COVID-19 by Blocking the Spike Glycoprotein and NSP14 of SARS-CoV-2 date: 2020-09-10 words: 3999.0 sentences: 219.0 pages: flesch: 52.0 cache: ./cache/cord-307227-x6xketcn.txt txt: ./txt/cord-307227-x6xketcn.txt summary: Here, we combine homology modeling, molecular docking, molecular dynamics simulation, and binding affinity calculations to determine potential targets for toremifene, a selective estrogen receptor modulator which we have previously identified as a SARS-CoV-2 inhibitor. These results suggest potential structural mechanisms for toremifene by blocking the spike protein and NSP14 of SARS-CoV-2, offering a drug candidate for COVID-19. 2, 3 In our initial network-based drug repurposing study, 4 we identified toremifene, another selective estrogen receptor modulator (SERM), as a strong candidate for the potential treatment of COVID-19. A drug repurposing study for SARS-CoV-1 5 indicated a low 50% effective concentration (EC 50 ) for toremifene, and noted that estrogen signaling may not be involved in the inhibitory pathway, similar to that of inhibition of Ebola. Future work will be needed to confirm these results; optimally, the determination of a cocrystal structure with Journal of Proteome Research pubs.acs.org/jpr Article NSP14 and/or the spike glycoprotein from SARS-CoV-2 with toremifene would be solved. abstract: [Image: see text] The global pandemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to the death of more than 675,000 worldwide and over 150,000 in the United States alone. However, there are currently no approved effective pharmacotherapies for COVID-19. Here, we combine homology modeling, molecular docking, molecular dynamics simulation, and binding affinity calculations to determine potential targets for toremifene, a selective estrogen receptor modulator which we have previously identified as a SARS-CoV-2 inhibitor. Our results indicate the possibility of inhibition of the spike glycoprotein by toremifene, responsible for aiding in fusion of the viral membrane with the cell membrane, via a perturbation to the fusion core. An interaction between the dimethylamine end of toremifene and residues Q954 and N955 in heptad repeat 1 (HR1) perturbs the structure, causing a shift from what is normally a long, helical region to short helices connected by unstructured regions. Additionally, we found a strong interaction between toremifene and the methyltransferase nonstructural protein (NSP) 14, which could be inhibitory to viral replication via its active site. These results suggest potential structural mechanisms for toremifene by blocking the spike protein and NSP14 of SARS-CoV-2, offering a drug candidate for COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32907334/ doi: 10.1021/acs.jproteome.0c00397 id: cord-329149-1giy1fow author: Martinez-Martin, Nadia title: Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions date: 2017-02-22 words: 11180.0 sentences: 487.0 pages: flesch: 27.0 cache: ./cache/cord-329149-1giy1fow.txt txt: ./txt/cord-329149-1giy1fow.txt summary: Despite SPR and related methods offering higher sensitivity for detection of transient Biochemical and MS PDGFR identified as a high affinity cell surface receptor for the CMV gHgLgO protein complex [21] Herpes simplex viruses (HSVs) Biophysical Secreted and plasma membrane-expressed glycoprotein G targets a specific set of human chemokines with high affinity [22] Human immunodeficiency virus type 1 (HIV) Despite the undoubted importance of the biochemical and biophysical approaches to the study of host-pathogen interactions, the aforementioned limitations have motivated the development of alternative technologies for large-scale analysis of ePPIs. From the initial utilization of microarrays for detection of PPI over a decade ago, human proteome chips containing thousands of recombinant proteins have been generated, some of which are now commercially available. abstract: Pathogens have evolved unique mechanisms to breach the cell surface barrier and manipulate the host immune response to establish a productive infection. Proteins exposed to the extracellular environment, both cell surface-expressed receptors and secreted proteins, are essential targets for initial invasion and play key roles in pathogen recognition and subsequent immunoregulatory processes. The identification of the host and pathogen extracellular molecules and their interaction networks is fundamental to understanding tissue tropism and pathogenesis and to inform the development of therapeutic strategies. Nevertheless, the characterization of the proteins that function in the host-pathogen interface has been challenging, largely due to the technical challenges associated with detection of extracellular protein interactions. This review discusses available technologies for the high throughput study of extracellular protein interactions between pathogens and their hosts, with a focus on mammalian viruses and bacteria. Emerging work illustrates a rich landscape for extracellular host-pathogen interaction and points towards the evolution of multifunctional pathogen-encoded proteins. Further development and application of technologies for genome-wide identification of extracellular protein interactions will be important in deciphering functional host-pathogen interaction networks, laying the foundation for development of novel therapeutics. url: https://www.ncbi.nlm.nih.gov/pubmed/28321417/ doi: 10.1155/2017/2197615 id: cord-263315-g7os15m1 author: Martins-da-Silva, Andrea title: Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response date: 2018-01-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Hematophagous insects transmit infectious diseases. Sand flies are vectors of leishmaniasis, but can also transmit viruses. We have been studying immune responses of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in the Americas. We identified a non-specific antiviral response in L. longipalpis LL5 embryonic cells when treated with non-specific double-stranded RNAs (dsRNAs). This response is reminiscent of interferon response in mammals. We are investigating putative effectors for this antiviral response. Secreted molecules have been implicated in immune responses, including interferon-related responses. We conducted a mass spectrometry analysis of conditioned medium from LL5 cells 24 and 48 h after dsRNA or mock treatment. We identified 304 proteins. At 24 h, 19 proteins had an abundance equal or greater than 2-fold change, while the levels of 17 proteins were reduced when compared to control cells. At the 48 h time point, these numbers were 33 and 71, respectively. The two most abundant secreted peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an interferon-inducible protein that mediates antiviral activity, and forskolin-binding protein (FKBP), a member of the immunophilin family, which mediates the effect of immunosuppressive drugs. The transcription profile of most candidates did not follow the pattern of secreted protein abundance. url: https://www.ncbi.nlm.nih.gov/pubmed/29346269/ doi: 10.3390/v10010043 id: cord-316983-h4mtpcyc author: Mathé-Hubert, Hugo title: Comparative venomics of Psyttalia lounsburyi and P. concolor, two olive fruit fly parasitoids: a hypothetical role for a GH1 β-glucosidase date: 2016-10-25 words: 8294.0 sentences: 425.0 pages: flesch: 51.0 cache: ./cache/cord-316983-h4mtpcyc.txt txt: ./txt/cord-316983-h4mtpcyc.txt summary: We have identified here the main venom proteins of two braconid wasps, Psyttalia lounsburyi (two strains from South Africa and Kenya) and P. To assess whether this variation between two figitid species that differ in their host range similarly exists in other parasitoid taxa, we compared here the venom composition of two braconid wasps, Psyttalia lounsburyi and P. This resulted in a total of 32 and 30 putative venom proteins for Pl and Pc respectively (Tables 1 and 2), whose relative abundance was compared using (i) the RPKM normalized number of Illumina reads from Pl and Pc venom apparatus, mapped to the assembled transcriptomes and (ii) the number of peptides matches in Mascot searches. Interestingly, most of the proteins identified in the proteomics of the reservoir (detection of the most abundant putative venom proteins only, data not shown), such as actin or paramyosin, had a predicted muscular function, as expected from microscopy observations (see above; Fig. 1 ). abstract: Venom composition of parasitoid wasps attracts increasing interest – notably molecules ensuring parasitism success on arthropod pests – but its variation within and among taxa is not yet understood. We have identified here the main venom proteins of two braconid wasps, Psyttalia lounsburyi (two strains from South Africa and Kenya) and P. concolor, olive fruit fly parasitoids that differ in host range. Among the shared abundant proteins, we found a GH1 β-glucosidase and a family of leucine-rich repeat (LRR) proteins. Olive is extremely rich in glycoside compounds that are hydrolyzed by β-glucosidases into defensive toxic products in response to phytophagous insect attacks. Assuming that Psyttalia host larvae sequester ingested glycosides, the injected venom GH1 β-glucosidase could induce the release of toxic compounds, thus participating in parasitism success by weakening the host. Venom LRR proteins are similar to truncated Toll-like receptors and may possibly scavenge the host immunity. The abundance of one of these LRR proteins in the venom of only one of the two P. lounsburyi strains evidences intraspecific variation in venom composition. Altogether, venom intra- and inter-specific variation in Psyttalia spp. were much lower than previously reported in the Leptopilina genus (Figitidae), suggesting it might depend upon the parasitoid taxa. url: https://doi.org/10.1038/srep35873 doi: 10.1038/srep35873 id: cord-034406-i1hbx3pz author: Matthews, Abigail A. title: Developing inhaled protein therapeutics for lung diseases date: 2020-10-30 words: 8739.0 sentences: 395.0 pages: flesch: 40.0 cache: ./cache/cord-034406-i1hbx3pz.txt txt: ./txt/cord-034406-i1hbx3pz.txt summary: Biologic therapeutics such as protein/polypeptide drugs are conventionally administered systemically via intravenous injection for the treatment of diseases including lung diseases, although this approach leads to low target site accumulation and the potential risk for systemic side effects. In comparison, topical delivery of protein drugs to the lung via inhalation is deemed to be a more effective approach for lung diseases, as proteins would directly reach the target in the lung while exhibiting poor diffusion into the systemic circulation, leading to higher lung drug retention and efficacy while minimising toxicity to other organs. This means that high concentrations of the protein drug can be attained in the lung via pulmonary delivery, suggesting that lower doses of inhaled protein can have an equivalent or even superior therapeutic effect for lung diseases when compared to the higher doses that would be needed from systemic administration [9] . abstract: Biologic therapeutics such as protein/polypeptide drugs are conventionally administered systemically via intravenous injection for the treatment of diseases including lung diseases, although this approach leads to low target site accumulation and the potential risk for systemic side effects. In comparison, topical delivery of protein drugs to the lung via inhalation is deemed to be a more effective approach for lung diseases, as proteins would directly reach the target in the lung while exhibiting poor diffusion into the systemic circulation, leading to higher lung drug retention and efficacy while minimising toxicity to other organs. This review examines the important considerations and challenges in designing an inhaled protein therapeutics for local lung delivery: the choice of inhalation device, structural changes affecting drug deposition in diseased lungs, clearance mechanisms affecting an inhaled protein drug’s lung accumulation, protein stability, and immunogenicity. Possible approaches to overcoming these issues will also be discussed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595758/ doi: 10.1186/s43556-020-00014-z id: cord-016652-x8t3lf1x author: Matthews, David title: Viruses and the Nucleolus date: 2011-05-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The nucleolus is a dynamic sub-nuclear structure integral to the function of a eukaryotic cell. Some of its major roles involve ribosome subunit biogenesis, RNA processing, cell cycle control and responding to cellular stress, such as infection. Our understanding of the relationship between viruses and the nucleolus has moved from a phenomenological approach describing protein localisation to functional studies involving genetic analysis and proteomic approaches. These advances have provided fundamental insights as to how and why the nucleolus is targeted by many different viruses both to usurp normal functioning and to recruit nucleolar proteins to facilitate virus replication. This knowledge has been exploited for therapeutic strategies involving targeted inhibition of virus replication and live-attenuated recombinant vaccines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121007/ doi: 10.1007/978-1-4614-0514-6_14 id: cord-259412-l8uta7du author: Mattossovich, Rosanna title: O(6)-alkylguanine-DNA Alkyltransferases in Microbes Living on the Edge: From Stability to Applicability date: 2020-04-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The genome of living cells is continuously exposed to endogenous and exogenous attacks, and this is particularly amplified at high temperatures. Alkylating agents cause DNA damage, leading to mutations and cell death; for this reason, they also play a central role in chemotherapy treatments. A class of enzymes known as AGTs (alkylguanine-DNA-alkyltransferases) protects the DNA from mutations caused by alkylating agents, in particular in the recognition and repair of alkylated guanines in O(6)-position. The peculiar irreversible self-alkylation reaction of these enzymes triggered numerous studies, especially on the human homologue, in order to identify effective inhibitors in the fight against cancer. In modern biotechnology, engineered variants of AGTs are developed to be used as protein tags for the attachment of chemical ligands. In the last decade, research on AGTs from (hyper)thermophilic sources proved useful as a model system to clarify numerous phenomena, also common for mesophilic enzymes. This review traces recent progress in this class of thermozymes, emphasizing their usefulness in basic research and their consequent advantages for in vivo and in vitro biotechnological applications. url: https://www.ncbi.nlm.nih.gov/pubmed/32326075/ doi: 10.3390/ijms21082878 id: cord-321013-8pkrg0mx author: McBride, Ruth title: The Coronavirus Nucleocapsid Is a Multifunctional Protein date: 2014-08-07 words: 10761.0 sentences: 476.0 pages: flesch: 44.0 cache: ./cache/cord-321013-8pkrg0mx.txt txt: ./txt/cord-321013-8pkrg0mx.txt summary: The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. The M protein is the main core shell component and a 16 amino acid domain (aa 237-252) on the CTD of M protein binds directly to N protein via an ionic interaction, leading to specific genome encapsidation in the budding viral particle [81] [82] [83] .The N protein therefore plays an essential structural role in the CoV virion through a network of interactions with (i) the genomic RNA; (ii) M protein and (iii) other N proteins. Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA abstract: The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. Recent studies have confirmed that N is a multifunctional protein. The aim of this review is to highlight the properties and functions of the N protein, with specific reference to (i) the topology; (ii) the intracellular localization and (iii) the functions of the protein. url: https://doi.org/10.3390/v6082991 doi: 10.3390/v6082991 id: cord-315531-2gc2dc46 author: McGarvey, Peter B. title: Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets date: 2009-09-25 words: 7016.0 sentences: 335.0 pages: flesch: 39.0 cache: ./cache/cord-315531-2gc2dc46.txt txt: ./txt/cord-315531-2gc2dc46.txt summary: (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. The centers have generated a heterogeneous set of experimental data using various technologies loosely defined as proteomic, but encompassing genomic, structural, immunology and protein interaction technologies, as well as more standard cell and molecular biology techniques used to validate potential targets identified via high-throughput methods. Here we describe in detail a protein-centric approach for systems integration of such a large and heterogeneous set of data from the NIAID Biodefense Proteomics program, and present scientific case studies to illustrate its application to facilitate the basic understanding of pathogen-host interactions and for the identification of potential candidates for therapeutic or diagnostic targets. abstract: The NIAID (National Institute for Allergy and Infectious Diseases) Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org) has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2) The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3) Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and prioritization of ten potential diagnostic targets from Bacillus anthracis. The integrative analysis across data sets from multiple centers can reveal potential functional significance and hidden relationships between pathogen and host proteins, thereby providing a systems approach to basic understanding of pathogenicity and target identification. url: https://www.ncbi.nlm.nih.gov/pubmed/19779614/ doi: 10.1371/journal.pone.0007162 id: cord-021393-9loesliv author: Meade, H.M. title: EXPRESSION OF RECOMBINANT PROTEINS IN THE MILK OF TRANSGENIC ANIMALS date: 2007-09-02 words: 8080.0 sentences: 416.0 pages: flesch: 48.0 cache: ./cache/cord-021393-9loesliv.txt txt: ./txt/cord-021393-9loesliv.txt summary: To date (1997) , probably more than 50 proteins have been expressed in the milk of transgenic mice, rats, rabbits, goats, sheep, pigs, and dairy cows. Transgenes containing sequences of several milk protein genes, reviewed by Maga and Murray (1995) and Echelard (1996) , have been used to direct the expression of exogenous proteins to the lactating mammary gland. Regulatory sequences from several milk-specific genes have been isolated and tested in transgenic animals: ovine ~-lactoglobulin; murine, rat, and rabbit whey acidic protein (WAP); bovine ~-sl casein; rat, rabbit, and goat f~-casein; and guinea pig, ovine, caprine, and bovine ~-lactalbumin. A 17.2 kbp region located upstream of the rabbit WAP gene directs high level expression of a functional human protein variant in transgenic mouse milk High level production of human growth hormone in the milk of transgenic mice: The upstream region of the whey acidic protein (WAP) gene targets transgene expression to the mammary gland abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149546/ doi: 10.1016/b978-012253840-7/50015-8 id: cord-280429-4fota9rl author: Medvedev, Kirill E. title: Functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold date: 2018-06-13 words: 7468.0 sentences: 465.0 pages: flesch: 49.0 cache: ./cache/cord-280429-4fota9rl.txt txt: ./txt/cord-280429-4fota9rl.txt summary: 10 However, structural analyses of virion architecture and coat protein topology have revealed unexpected similarities, not visible in sequence comparisons, suggesting a common origin for viruses that infect hosts residing in different domains of life. In this current work, we provide functional and evolutionary analysis of viral proteins containing a Rossmann-like fold that can be found in the Evolutionary Classification of protein Domains (ECOD) database developed in our lab. The structures represented gene products from 21 viral taxonomical families with host ranges from all kingdoms of life (http://prodata.swmed.edu/rossmann_fold/viruses/). Our analysis detected 14 different bacterial virus structure topology types defined by ECOD T-groups that contain a Rossmann-like fold (Fig. 2, 12 topology groups shown). Like the bacterial and eukaryotic branches in the tree of life, the Archea are host to a multitude of Functional and Evolutionary Analysis of Viral Proteins viruses. 61 Among viral protein structures containing the minimal Rossmann fold, 14 protein families are known helicases (http://prodata.swmed.edu/ross-mann_fold/viruses/). abstract: Viruses are the most abundant life form and infect practically all organisms. Consequently, these obligate parasites are a major cause of human suffering and economic loss. Rossmann‐like fold is the most populated fold among α/β‐folds in the Protein Data Bank and proteins containing Rossmann‐like fold constitute 22% of all known proteins 3D structures. Thus, analysis of viral proteins containing Rossmann‐like domains could provide an understanding of viral biology and evolution as well as could propose possible targets for antiviral therapy. We provide functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold found in the evolutionary classification of protein domains (ECOD) database developed in our lab. We identified 81 protein families of bacterial, archeal, and eukaryotic viruses in light of their evolution‐based ECOD classification and Pfam taxonomy. We defined their functional significance using enzymatic EC number assignments as well as domain‐level family annotations. url: https://www.ncbi.nlm.nih.gov/pubmed/29722076/ doi: 10.1002/pro.3438 id: cord-277811-j58qvyum author: Mehrani, Hossein title: Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis date: 2011-01-07 words: 4086.0 sentences: 226.0 pages: flesch: 51.0 cache: ./cache/cord-277811-j58qvyum.txt txt: ./txt/cord-277811-j58qvyum.txt summary: title: Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis Haptoglobin α1 chain isoforms (spots 21, 22 and 23) were only detected in the plasma of the severe lung diseases patients but were not detectable in healthy controls ( Figure 2B and 2C). In this study we present plasma proteome analysis of SM exposed patients compared to the healthy controls. In our recent study of BAL fluid proteomics patterns in SM exposed patients we also found that haptoglobin isoforms were significantly elevated in moderate and severe lung disease patients compared to mild and healthy controls [13] . In conclusion, this study complements our previous BAL fluid proteome analysis of patients exposed to SM gas which resulted in identification of number of differentially expressed proteins. Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis abstract: INTRODUCTION: Sulfur mustard "bis (2-chlroethyl) sulphide" (SM) is a chemical warfare agent that remains a threat to human health. The aim of this study was to identify protein expression signature or biomarkers that reflect chronic lung damages induced by SM exposure. METHODS: Prior to analysis, plasma was fractionated using ethanol precipitation. Using two dimensional SDS-PAGE; fractionated protein profiles of 20 healthy and 20 exposed patients with lung diseases were established. Selected protein spots were successfully identified with MALDI TOF MS/MS. RESULTS: The results show that α1 haptoglobin isoforms were detected in plasma of the all lung disease patients but none of the healthy controls. Amyloid A1 isoforms was also detected in plasma of the lung disease patients but none of the healthy controls. Moreover, low molecular weight proteins were enriched in ethanol supernatant compared to ethanol precipitate. CONCLUSION: Our present results and previous studies suggest that ongoing tissue remodeling is involved in SM exposed lung damage patients. These finding might improve patient care and suitable therapies. url: https://www.ncbi.nlm.nih.gov/pubmed/21906349/ doi: 10.1186/1559-0275-8-2 id: cord-335915-2apj4qy9 author: Melillo, Alessandro title: Applications of Serum Protein Electrophoresis in Exotic Pet Medicine date: 2013-01-22 words: 5404.0 sentences: 225.0 pages: flesch: 43.0 cache: ./cache/cord-335915-2apj4qy9.txt txt: ./txt/cord-335915-2apj4qy9.txt summary: The main difference between the 2 products is the absence in the serum of fribrinogen, the protein involved in the processes of coagulation; the concentration of total solids of the plasma is thus slightly higher than that of serum (about 5%) and the electrophoretic pattern from it will result in a higher incidence of b-globulin fraction where the fibrinogen normally migrates. In rabbits, the normal Serum Protein Electrophoresis (SPE) pattern lacks a clear distinction between b1-globulins and b2-globulins, as present in dogs and cats, but when gammopathies in the b region occur, usually an extension of the electrophoretic band is seen, with consequent demarcation of the 2 peaks. The first studies of serum proteins in birds were performed on domestic chickens, showing many similarities with the layout of mammals (eg, the production of APPs 18, 19 ), but also several differences: the widespread presence of prealbumin, for example, the lowest concentration of g-globulin, and conversely the more marked response to inflammatory stimuli in the b-globulin field. abstract: Serum Protein Electrophoresis (SPE) is a useful diagnostic and prognostic tool in human and companion animals medicine: several experiences show that it can be useful in exotic practice as well. The fundamentals of SPE interpretation as well as some normal and pathological patterns for the species most commonly seen in practice are provided. url: https://doi.org/10.1016/j.cvex.2012.11.002 doi: 10.1016/j.cvex.2012.11.002 id: cord-334220-sqvfr31q author: Messina, Francesco title: Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date: 2020-11-03 words: 4218.0 sentences: 237.0 pages: flesch: 44.0 cache: ./cache/cord-334220-sqvfr31q.txt txt: ./txt/cord-334220-sqvfr31q.txt summary: The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. In SFigure For KEGG database the gene enrichment analysis on interactomes of NS7b, ORF1a, ORF3a and ORF8 showed pathway clusters highly significant and consistent with possible pathogenic mechanisms, such as the activation of the complement and of the coagulative cascade, (29) and the TGF-β-dominated immune response (30) . We identified different host response induced by specific proteins of SARS-CoV-2, underlining the important role of ORF3a and ORF8 in phenotypes of severe COVID-19 patients. abstract: In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level. Host conditions and comorbidities were identified as risk factors for severe and fatal disease courses, but the mechanisms of interaction between host and SARS-CoV-2 determining the grade of COVID- 19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred on published PPI, using an explorative algorithm (Random Walk with Restart) triggered by all the 28 proteins of SARS-CoV-2, or each single viral protein one-by-one. The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, an explorative network-based approach was applied to Bradykinin Storm, highlighting a possible direct action of ORF3a and NS7b to enhancing this condition. This network-based model for SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. url: https://doi.org/10.1101/2020.11.03.366666 doi: 10.1101/2020.11.03.366666 id: cord-332784-xkc89uaz author: Mishra, Shashank Shekhar title: Computational investigation of potential inhibitors of novel coronavirus 2019 through structure-based virtual screening, molecular dynamics and density functional theory studies date: 2020-07-15 words: 4245.0 sentences: 234.0 pages: flesch: 49.0 cache: ./cache/cord-332784-xkc89uaz.txt txt: ./txt/cord-332784-xkc89uaz.txt summary: The novel hit molecules identified from docking study were selected based on the docking score, binding energy calculations, and their other interactions with amino acid residues. To analyze the structural stability of the COVID-19 main protease protein-ligand complexes, molecular dynamics simulations were carried out by using Desmond in the presence of the POPC bilayer membrane (Shekhar et al., 2019) . The selected five potential hit molecules in the binding site of protease protein, interacting with amino acid residues Phe140, Gly143, Thr26, Thr190, Glu166, Pro168, Met165 and Leu141 with a docking score of À7.524 and À6.711 kcal/mol. It is found that the hydrogen bonds with Glu166 and hydrophobic interactions with Pro168, Leu167, Met 49, His41are major contributing factor for stabilizing hit molecule ZINC13144609 at the binding site which is in accordance with our docking result. abstract: Despite the intensive research efforts towards antiviral drug against COVID-19, no potential drug or vaccines has not yet discovered. Initially, the binding site of COVID-19 main protease was predicted which located between regions 2 and 3. Structure-based virtual screening was performed through a hierarchal mode of elimination technique after generating a grid box. This led to the identification of five top hit molecules that were selected on the basis of docking score and visualization of non-bonding interactions. The docking results revealed that the hydrogen bonding and hydrophobic interactions are the major contributing factors in the stabilization of complexes. The docking scores were found between −7.524 and −6.711 kcal/mol indicating strong ligand-protein interactions. Amino acid residues Phe140, Leu141, Gly143, Asn142, Thr26, Glu166 and Thr190 (hydrogen bonding interactions) and Phe140, Cys145, Cys44, Met49, Leu167, Pro168, Met165, Val42, Leu27 and Ala191 (hydrophobic interactions) formed the binding pocket of COVID-19 main protease. From identified hits, ZINC13144609 and ZINC01581128 were selected for atomistic MD simulation and density functional theory calculations. MD simulation results confirm that the protein interacting with both hit molecules is stabilized in the chosen POPC lipid bilayer membrane. The presence of lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) in the hydrophobic region of the hit molecules leads to favorable ligand-protein contacts. The calculated pharmacokinetic descriptors were found to be in their acceptable range and therefore confirming their drug-like properties. Hence, the present investigation can serve as the basis for designing and developing COVID-19 inhibitors. Communicated by Ramaswamy H. Sarma url: https://www.ncbi.nlm.nih.gov/pubmed/32666910/ doi: 10.1080/07391102.2020.1791957 id: cord-018437-yjvwa1ot author: Mitchell, Michael title: Taxonomy date: 2013-08-26 words: 9283.0 sentences: 561.0 pages: flesch: 48.0 cache: ./cache/cord-018437-yjvwa1ot.txt txt: ./txt/cord-018437-yjvwa1ot.txt summary: Classifi cation is based on the genomic nucleic acid used by the virus (DNA or RNA), strandedness (single or double stranded), and method of replication. The nucleocapsids of some viruses are surrounded by envelopes composed of lipid bilayers and host-or viral-encoded proteins. The sequence of negative-sense ssRNA is complementary to the coding sequence for translation, so mRNA must be synthesized by RNA polymerase, typically carried within the virion, before translation into viral proteins. Among the families of viruses able to infect humans and other vertebrate hosts, there are many species that target and cause disease in the lung. The nucleocapsid is surrounded by an envelope derived from host-cell membrane and viral envelope proteins, including hepatitis B surface antigen. The genome of human parainfl uenza viruses is ~15 kb in length with an organization and six reading frames (N, P, M, F, HN, L) typical of the Paramyxoviridae (Karron and Collins 2007 ) . abstract: This chapter addresses the classification and taxonomy of viruses with special attention to viruses that show pneumotropic properties. Information provided in this chapter supplements that provided in other chapters in Parts II–V of this volume that discuss individual viral pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123310/ doi: 10.1007/978-3-642-40605-8_3 id: cord-007648-tm0hn0hz author: Mockett, A.P.Adrian title: Envelope proteins of avian infectious bronchitis virus: Purification and biological properties date: 2002-12-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Immunoadsorbents, made with monoclonal antibodies, were used to purify the spike and membrane proteins of infectious bronchitis virus (IBV). The purified proteins were inoculated into rabbits to produce antisera. The rabbit anti-spike sera neutralized the infectivity of the virus whereas the anti-membrane sera did not. IBV-infected chickens produced antibodies to both the spike and membrane proteins. Both these antibodies were at their highest concentration about 9–11 days after inoculation, whereas neutralizing antibodies were present only at very low concentrations at that time. Neutralizing antibodies were at their highest concentration 21 days after inoculation. A second inoculation of virus at 42 days induced an anamnestic antibody response to the spike and membrane proteins and also for the neutralizing antibodies. The neutralizing, anti-spike and anti-membrane antibodies all reached highest concentrations 7–11 days after this inoculation. The advantages of purifying viral proteins using affinity chromatography with monoclonal antibodies are discussed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119818/ doi: 10.1016/0166-0934(85)90138-7 id: cord-304953-ntg8w5k4 author: Modis, Yorgo title: Relating structure to evolution in class II viral membrane fusion proteins date: 2014-02-11 words: 3699.0 sentences: 177.0 pages: flesch: 44.0 cache: ./cache/cord-304953-ntg8w5k4.txt txt: ./txt/cord-304953-ntg8w5k4.txt summary: The striking structural similarity between the flavivirus E proteins and RVFV G -which extends to the mode of dimerization even though E and Gc dimers form different types of icosahedral lattices -is strongly suggestive of a common evolutionary origin for certain envelope proteins within the Bunyaviridae and Flaviviridae families. The conservation of an a-helical coiled coil architecture in class I viral proteins and in the SNARE family of intracellular vesicle fusion proteins provides a compelling precedent for the evolutionary transfer of a structural membrane fusion fold between host and virus during evolution. . This study showed that the Gc envelope protein from Rift Valley fever virus (from the Bunyaviridae family) has a class II fold with striking resemblances to that of E from dengue and other flaviviruses, including a propensity to form head-to-tail dimers with a hydrophobic membrane anchor, or fusion loop buried at the dimer interface. abstract: Enveloped viruses must fuse their lipid membrane to a cellular membrane to deliver the viral genome into the cytoplasm for replication. Viral envelope proteins catalyze this critical membrane fusion event. They fall into at least three distinct structural classes. Class II fusion proteins have a conserved three-domain architecture and are found in many important viral pathogens. Until 2013, class II proteins had only been found in flaviviruses and alphaviruses. However, in 2013 a class II fusion protein was discovered in the unrelated phlebovirus genus, and two unexpectedly divergent envelope proteins were identified in families that also contain prototypical class II proteins. The structural relationships of newly identified class II proteins, reviewed herein, shift the paradigm for how these proteins evolved. url: https://doi.org/10.1016/j.coviro.2014.01.009 doi: 10.1016/j.coviro.2014.01.009 id: cord-333757-h12aozg2 author: Modis, Yorgo title: Class II Fusion Proteins date: 2013-07-10 words: 6790.0 sentences: 393.0 pages: flesch: 51.0 cache: ./cache/cord-333757-h12aozg2.txt txt: ./txt/cord-333757-h12aozg2.txt summary: Furthermore, all available crystal structures of class II fusion proteins lack the ''stem'' region, 43 a 30-55 amino acid linker between Domain III and the C-terminal transmembrane anchor (Figs. The three-dimensional structures of four class II fusion proteins in their postfusion states 29,55,56,94 reveal striking differences from the prefusion forms (Fig. 3) , and suggest a 13 and B) two SFV E1 12 molecules in the prefusion conformation as found on the viral surface, viewed perpendicular to the viral membrane. 29, 55 A deep channel extends from the C-terminus of the crystallized fragment along the intersubunit contact between domains II to the fusion loops, in both the dengue and Semliki Forest virus postfusion trimer structures. The recently determined crystal structures of class II fusion proteins in pre 10,12-14 and postfusion 29, 55, 56 conformations offer the first direct views of fusion anchors-in this case, the fusion loops-as they insert into a target membrane (Fig. 4) . abstract: Enveloped viruses rely on fusion proteins in their envelope to fuse the viral membrane to the host-cell membrane. This key step in viral entry delivers the viral genome into the cytoplasm for replication. Although class II fusion proteins are genetically and structurally unrelated to class I fusion proteins, they use the same physical principles and topology as other fusion proteins to drive membrane fusion. Exposure of a fusion loop first allows it to insert into the host-cell membrane. Conserved hydrophobic residues in the fusion loop act as an anchor, which penetrates only partway into the outer bilayer leaflet of the host-cell membrane. Subsequent folding back of the fusion protein on itself directs the C-terminal viral transmembrane anchor towards the fusion loop. This fold-back forces the host-cell membrane (held by the fusion loop) and the viral membrane (held by the C-terminal transmembrane anchor) against each other, resulting in membrane fusion. In class II fusion proteins, the fold-back is triggered by the reduced pH of an endosome, and is accompanied by the assembly of fusion protein monomers into trimers. The fold-back occurs by domain rearrangement rather than by an extensive refolding of secondary structure, but this domain rearrangement and the assembly of monomers into trimers together bury a large surface area. The energy that is thus released exerts a bending force on the apposed viral and cellular membranes, causing them to bend towards each other and, eventually, to fuse. url: https://www.ncbi.nlm.nih.gov/pubmed/23884590/ doi: 10.1007/978-1-4614-7651-1_8 id: cord-327199-ggomuomb author: Moerdyk-Schauwecker, Megan title: Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions date: 2014-08-08 words: 6425.0 sentences: 288.0 pages: flesch: 43.0 cache: ./cache/cord-327199-ggomuomb.txt txt: ./txt/cord-327199-ggomuomb.txt summary: In another example, the presence of host complement control proteins such as CD46, CD55 and CD59 in the viral envelope has been shown to protect against antibody dependent complement mediated virus lysis in several viruses including human T cell leukemia/ lymphoma virus type I [16] , human cytomegalovirus [16] , hepatitis C virus [17] , HIV-1 [18, 19] , extracellular enveloped vaccinia virus [20] , simian virus 5 [21] and mumps virus [21] . As discussed in the previous section, proteins not associated with the interior of the virion, including proteins embedded in the host derived viral envelope, can be identified by their absence in ProK treated samples or by a size shift upon ProK treatment. While many of the proteins identified in VSV virions appear to be associated with viral assembly, budding or the host-derived viral envelope, they may also have additional functions that affect virus replication. abstract: Virus particles (virions) often contain not only virus-encoded but also host-encoded proteins. Some of these host proteins are enclosed within the virion structure, while others, in the case of enveloped viruses, are embedded in the host-derived membrane. While many of these host protein incorporations are likely accidental, some may play a role in virus infectivity, replication and/or immunoreactivity in the next host. Host protein incorporations may be especially important in therapeutic applications where large numbers of virus particles are administered. Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and a candidate vaccine, gene therapy and oncolytic vector. Using mass spectrometry, we previously examined cell type dependent host protein content of VSV virions using intact (“whole”) virions purified from three cell lines originating from different species. Here we aimed to determine the localization of host proteins within the VSV virions by analyzing: i) whole VSV virions; and ii) whole VSV virions treated with Proteinase K to remove all proteins outside the viral envelope. A total of 257 proteins were identified, with 181 identified in whole virions and 183 identified in Proteinase K treated virions. Most of these proteins have not been previously shown to be associated with VSV. Functional enrichment analysis indicated the most overrepresented categories were proteins associated with vesicles, vesicle-mediated transport and protein localization. Using western blotting, the presence of several host proteins, including some not previously shown in association with VSV (such as Yes1, Prl1 and Ddx3y), was confirmed and their relative quantities in various virion fractions determined. Our study provides a valuable inventory of virion-associated host proteins for further investigation of their roles in the replication cycle, pathogenesis and immunoreactivity of VSV. url: https://www.ncbi.nlm.nih.gov/pubmed/25105980/ doi: 10.1371/journal.pone.0104688 id: cord-295351-0zr2e8lh author: Mohd Ropidi, Muhammad Izzuddin title: Endoplasmic reticulum: a focal point of Zika virus infection date: 2020-01-20 words: 7845.0 sentences: 389.0 pages: flesch: 35.0 cache: ./cache/cord-295351-0zr2e8lh.txt txt: ./txt/cord-295351-0zr2e8lh.txt summary: Following ZIKV infection, the accumulation of misfolded virus polyproteins in the ER lumen overwhelms the ER protein-folding capacity leading to ER stress and triggers the activation of the UPR (Fig. 2) [47] . Following the dissociation of GRP78 that unmasks the GLS, ATF6 translocate to the Golgi apparatus and undergoes sequential proteolytic processing by Fig. 2 ZIKV-induced ER stress initiates host cell unfolded protein response (UPR). ZIKV infection induces ER stress due to the increased amount of unfolded/misfolded viral (red strand) and host cell (grey strand) protein aggregates in the ER lumen. To summarize, ZIKV virus bypasses the UPR by inhibiting stress granules assembly and reticulophagy to ensure continuous viral protein translation and virion production while simultaneously protecting the virus from host cell defense mechanisms. abstract: Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family. It is an arbovirus that can cause congenital abnormalities and is sexually transmissible. A series of outbreaks accompanied by unexpected severe clinical complications have captured medical attention to further characterize the clinical features of congenital ZIKV syndrome and its underlying pathophysiological mechanisms. Endoplasmic reticulum (ER) and ER-related proteins are essential in ZIKV genome replication. This review highlights the subcellular localization of ZIKV to the ER and ZIKV modulation on the architecture of the ER. This review also discusses ZIKV interaction with ER proteins such as signal peptidase complex subunit 1 (SPCS1), ER membrane complex (EMC) subunits, and ER translocon for viral replication. Furthermore, the review covers several important resulting effects of ZIKV infection to the ER and cellular processes including ER stress, reticulophagy, and paraptosis-like death. Pharmacological targeting of ZIKV-affected ER-resident proteins and ER-associated components demonstrate promising signs of combating ZIKV infection and rescuing host organisms from severe neurologic sequelae. url: https://www.ncbi.nlm.nih.gov/pubmed/31959174/ doi: 10.1186/s12929-020-0618-6 id: cord-289124-6w2zvvj1 author: Mok, Lawrence title: Proteomic analysis of Pteropus alecto kidney cells in response to the viral mimic, Poly I:C date: 2015-11-02 words: 5444.0 sentences: 356.0 pages: flesch: 57.0 cache: ./cache/cord-289124-6w2zvvj1.txt txt: ./txt/cord-289124-6w2zvvj1.txt summary: Here, we investigated the differential protein expression of immortalised Pteropus alecto kidney cells (PaKiT03) following transfection with the viral mimic, Poly I:C. Two complementary proteomic approaches, difference gel electrophoresis (DIGE) and isobaric tagging for relative and absolute quantitation (iTRAQ) were used to quantify changes in protein expression following Poly I:C stimulation at 4, 8 and 20 hr post treatment (hpt). Through iTRAQ analysis we show that Poly I:C up-regulates key glycolytic enzymes at 4 hpt within PaKiT03 cells. The analysis with DIGE of Poly I:C transfected PaKiT03 cells showed over 215 individual spots differentially regulated, however only 25 spots could be unambiguously identified by LC-MS/MS. We further assessed the response of three glycolytic enzymes, α-enolase (Eno1), phosphoglycerate mutase 1 (Pgam1) and triosephosphate isomerase 1 (Tpi1) to Poly I:C across two human (HEK293T and HeLa) and two bat cell lines (PaKiT03, PaLuT02) using immunodetection. abstract: BACKGROUND: Bats are recognised as an important reservoir for a number of highly pathogenic zoonotic viruses. While many of these viruses cause severe and often fatal disease in humans, bats are able to coexist with these viruses without clinical signs of disease. The mechanism conferring this antiviral response is not fully understood. Here, we investigated the differential protein expression of immortalised Pteropus alecto kidney cells (PaKiT03) following transfection with the viral mimic, Poly I:C. Two complementary proteomic approaches, difference gel electrophoresis (DIGE) and isobaric tagging for relative and absolute quantitation (iTRAQ) were used to quantify changes in protein expression following Poly I:C stimulation at 4, 8 and 20 hr post treatment (hpt). RESULTS: The expression of ISG54 gene, a known responder to virus infection and Poly I:C treatment, was significantly induced in transfected cells compared with mock-transfected cells. Through iTRAQ analysis we show that Poly I:C up-regulates key glycolytic enzymes at 4 hpt within PaKiT03 cells. In contrast, at 20 hpt PaKiT03 cells down-regulated ribosomal subunit proteins. The analysis with DIGE of Poly I:C transfected PaKiT03 cells showed over 215 individual spots differentially regulated, however only 25 spots could be unambiguously identified by LC-MS/MS. Immunoblotting confirmed the up-regulation of Eno1 and Tpi1 in PaKiT03 cells following Poly I:C transfection. A comparison with human cells (HEK293T and HeLa) and one additional bat cell line (PaLuT02), demonstrated that glycolytic pathways are also induced in these cell types, but at different intensities. CONCLUSION: The two techniques, DIGE and iTRAQ identified largely overlapping sets of differentially expressed proteins, however DIGE unambiguously identified significantly less proteins than iTRAQ. Poly I:C induced a rapid metabolic shift towards glycolysis within the PaKiT03 cells at 4 hpt, presumably as a consequence of increased energy requirements. On the other hand ribosomal subunit proteins were seen as down-regulated by iTRAQ, these proteins may be the limiting factors in the translational machinery available for virus replication. This study provides new insight into the antiviral response of bat cells, highlighting the importance of energy metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12953-015-0081-6) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1186/s12953-015-0081-6 doi: 10.1186/s12953-015-0081-6 id: cord-000642-mkwpuav6 author: Moreira, Rebeca title: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing date: 2012-04-19 words: 6848.0 sentences: 372.0 pages: flesch: 45.0 cache: ./cache/cord-000642-mkwpuav6.txt txt: ./txt/cord-000642-mkwpuav6.txt summary: title: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum. Moreover, a few transcripts encoded by genes putatively involved in the clam immune response against Perkinsus olseni have been reported by cDNA library sequencing [18] . philippinarum transcriptome and another four bivalve species sequences were analyzed by comparative genomics (Crassostrea gigas of the family Ostreidae, Bathymodiolus azoricus and Mytilus galloprovincialis of the family Mytilidae and Laternula elliptica of the family Laternulidae). abstract: BACKGROUND: The Manila clam (Ruditapes philippinarum) is a worldwide cultured bivalve species with important commercial value. Diseases affecting this species can result in large economic losses. Because knowledge of the molecular mechanisms of the immune response in bivalves, especially clams, is scarce and fragmentary, we sequenced RNA from immune-stimulated R. philippinarum hemocytes by 454-pyrosequencing to identify genes involved in their immune defense against infectious diseases. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput deep sequencing of R. philippinarum using 454 pyrosequencing technology yielded 974,976 high-quality reads with an average read length of 250 bp. The reads were assembled into 51,265 contigs and the 44.7% of the translated nucleotide sequences into protein were annotated successfully. The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. We have found sequences from molecules never described in bivalves before, especially in the complement pathway where almost all the components are present. CONCLUSIONS: This study represents the first transcriptome analysis using 454-pyrosequencing conducted on R. philippinarum focused on its immune system. Our results will provide a rich source of data to discover and identify new genes, which will serve as a basis for microarray construction and the study of gene expression as well as for the identification of genetic markers. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334963/ doi: 10.1371/journal.pone.0035009 id: cord-265887-g5zhoyo9 author: Mukherjee, Shruti title: Host-membrane interacting interface of the SARS coronavirus envelope protein: Immense functional potential of C-terminal domain date: 2020-08-11 words: 9085.0 sentences: 538.0 pages: flesch: 41.0 cache: ./cache/cord-265887-g5zhoyo9.txt txt: ./txt/cord-265887-g5zhoyo9.txt summary: (56) Apart from these highly conserved sequences throughout the genus, there are distinct potent glycosylation sites along the stretch that can serve as chaperone interacting motifs to help in the protein folding and/or aid in J o u r n a l P r e -p r o o f Journal Pre-proof trafficking along with the cellular machinery.(57) Glycosylation of particular asparagine residues (Asn 45, Asn 48, Asn 64, and Asn 68) in the SARS-CoV has been shown to be crucial in maintaining the proteinoligomerization events associated with the host membranes. (41) The formation of a disulfide bond may also play a crucial role in the oligomerization of the E protein, forming stable dimers, trimers, and pentamers depending on its functional requirement.(105) Thus even though the TMD spans the lipid bilayer, the CxxC motif could serve as an essential key to defining the membrane-associated oligomerization events-providing newer targets for preemptive therapeutic intervention. abstract: The Envelope (E) protein in SARS Coronavirus (CoV) is a small structural protein, incorporated as part of the envelope. A major fraction of the protein has been known to be associated with the host membranes, particularly organelles related to intracellular trafficking, prompting CoV packaging and propagation. Studies have elucidated the central hydrophobic transmembrane domain of the E protein being responsible for much of the viroporin activity in favor of the virus. However, newer insights into the organizational principles at the membranous compartments within the host cells suggest further complexity of the system. The lesser hydrophobic Carboxylic-terminal of the protein harbors interesting amino acid sequences- suggesting at the prevalence of membrane-directed amyloidogenic properties that remains mostly elusive. These highly conserved segments indicate at several potential membrane-associated functional roles that can redefine our comprehensive understanding of the protein. This should prompt further studies in designing and characterizing of effective targeted therapeutic measures. url: https://api.elsevier.com/content/article/pii/S0301462220301605 doi: 10.1016/j.bpc.2020.106452 id: cord-271642-i71g2tmd author: Mullen, Lisa M. title: Phage display in the study of infectious diseases date: 2006-02-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Microbial infections are dependent on the panoply of interactions between pathogen and host and identifying the molecular basis of such interactions is necessary to understand and control infection. Phage display is a simple functional genomic methodology for screening and identifying protein–ligand interactions and is widely used in epitope mapping, antibody engineering and screening for receptor agonists or antagonists. Phage display is also used widely in various forms, including the use of fragment libraries of whole microbial genomes, to identify peptide–ligand and protein–ligand interactions that are of importance in infection. In particular, this technique has proved successful in identifying microbial adhesins that are vital for colonization. url: https://api.elsevier.com/content/article/pii/S0966842X06000199 doi: 10.1016/j.tim.2006.01.006 id: cord-324640-2zhaknbi author: Munday, Diane C. title: Quantitative Proteomic Analysis of A549 Cells Infected with Human Respiratory Syncytial Virus date: 2010-07-20 words: 12318.0 sentences: 588.0 pages: flesch: 39.0 cache: ./cache/cord-324640-2zhaknbi.txt txt: ./txt/cord-324640-2zhaknbi.txt summary: Although RNA synthesis and virus assembly occur in the cytoplasm, HRSV is known to induce nuclear responses in the host cell as replication alters global gene expression. More recently, 2DE was used to compare the potential effect of several different negative strand RNA viruses, including HRSV, parainfluenza virus, human metap-neumovirus, measles virus, and influenza virus, on the host cell proteome with common changes in proteins involved with apoptosis and endoplasmic reticulum stress being highlighted (27) . Together, the indirect immunofluorescence confocal microscopy images supported the observations from the quantitative proteomic analysis that the abundance of mitochondrial proteins (particularly pore proteins) was altered in HRSV-infected cells. Potential Disruption of Proteins Involved in Nucleocytoplasmic Trafficking-Network pathway analysis indicated that the abundance of nuclear pore complex components and proteins involved in the nucleocytoplasmic trafficking of proteins and RNA differed between HRSV-infected and mock-infected cells (Fig. 4) . abstract: Human respiratory syncytial virus (HRSV) is a major cause of pediatric lower respiratory tract disease to which there is no vaccine or efficacious chemotherapeutic strategy. Although RNA synthesis and virus assembly occur in the cytoplasm, HRSV is known to induce nuclear responses in the host cell as replication alters global gene expression. Quantitative proteomics was used to take an unbiased overview of the protein changes in transformed human alveolar basal epithelial cells infected with HRSV. Underpinning this was the use of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS, which allowed the direct and simultaneous identification and quantification of both cellular and viral proteins. To reduce sample complexity and increase data return on potential protein localization, cells were fractionated into nuclear and cytoplasmic extracts. This resulted in the identification of 1,140 cellular proteins and six viral proteins. The proteomics data were analyzed using Ingenuity Pathways Analysis to identify defined canonical pathways and functional groupings. Selected data were validated using Western blot, direct and indirect immunofluorescence confocal microscopy, and functional assays. The study served to validate and expand upon known HRSV-host cell interactions, including those associated with the antiviral response and alterations in subnuclear structures such as the nucleolus and ND10 (promyelocytic leukemia bodies). In addition, novel changes were observed in mitochondrial proteins and functions, cell cycle regulatory molecules, nuclear pore complex proteins and nucleocytoplasmic trafficking proteins. These data shed light into how the cell is potentially altered to create conditions more favorable for infection. Additionally, the study highlights the application and advantage of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS for the analysis of virus-host interactions. url: https://www.ncbi.nlm.nih.gov/pubmed/20647383/ doi: 10.1074/mcp.m110.001859 id: cord-265087-g4k6pc82 author: Munteanu, Cristian Robert title: Natural/random protein classification models based on star network topological indices date: 2008-10-21 words: 3890.0 sentences: 215.0 pages: flesch: 52.0 cache: ./cache/cord-265087-g4k6pc82.txt txt: ./txt/cord-265087-g4k6pc82.txt summary: In conclusion, this study extends for the first time the classical TIs to protein star network TIs by proposing a model that can predict if a protein/fragment of protein is natural or random using only the amino acid sequence data. Using graphic approaches to study biological systems can provide useful insights, as indicated by many previous studies on a series of important biological topics, such as enzyme-catalyzed reactions (Andraos, 2008; Chou, 1989; Forsen, 1980, 1981; Chou and Liu, 1981; Chou et al., 1979; King and Altman, 1956; Kuzmic et al., 1992; Myers and Palmer, 1985; Zhou and Deng, 1984) , protein folding kinetics (Chou, 1990) , inhibition kinetics of processive nucleic acid polymerases and nucleases (Althaus et al., 1993a (Althaus et al., , b, c, 1994a (Althaus et al., , b, 1996 Chou et al., 1994) , analysis of codon usage (Chou and Zhang, 1992; Chou, 1993, 1994) , base frequencies in the anti-sense strands , and analysis of DNA sequence (Qi et al., 2007) . abstract: Abstract The development of the complex network graphs permits us to describe any real system such as social, neural, computer or genetic networks by transforming real properties in topological indices (TIs). This work uses Randic's star networks in order to convert the protein primary structure data in specific topological indices that are used to construct a natural/random protein classification model. The set of natural proteins contains 1046 protein chains selected from the pre-compiled CulledPDB list from PISCES Dunbrack's Web Lab. This set is characterized by a protein homology of 20%, a structure resolution of 1.6Å and R-factor lower than 25%. The set of random amino acid chains contains 1046 sequences which were generated by Python script according to the same type of residues and average chain length found in the natural set. A new Sequence to Star Networks (S2SNet) wxPython GUI application (with a Graphviz graphics back-end) was designed by our group in order to transform any character sequence in the following star network topological indices: Shannon entropy of Markov matrices, trace of connectivity matrices, Harary number, Wiener index, Gutman index, Schultz index, Moreau–Broto indices, Balaban distance connectivity index, Kier–Hall connectivity indices and Randic connectivity index. The model was constructed with the General Discriminant Analysis methods from STATISTICA package and gave training/predicting set accuracies of 90.77% for the forward stepwise model type. In conclusion, this study extends for the first time the classical TIs to protein star network TIs by proposing a model that can predict if a protein/fragment of protein is natural or random using only the amino acid sequence data. This classification can be used in the studies of the protein functions by changing some fragments with random amino acid sequences or to detect the fake amino acid sequences or the errors in proteins. These results promote the use of the S2SNet application not only for protein structure analysis but also for mass spectroscopy, clinical proteomics and imaging, or DNA/RNA structure analysis. url: https://api.elsevier.com/content/article/pii/S002251930800369X doi: 10.1016/j.jtbi.2008.07.018 id: cord-327744-5k8np850 author: Munteanu, Cristian Robert title: Multi-target QPDR classification model for human breast and colon cancer-related proteins using star graph topological indices date: 2009-03-21 words: 4738.0 sentences: 277.0 pages: flesch: 57.0 cache: ./cache/cord-327744-5k8np850.txt txt: ./txt/cord-327744-5k8np850.txt summary: In conclusion, we shown that, using simple input data such is the primary protein sequence and the simples linear analysis, it is possible to obtain accurate classification models that can predict if a new protein related with two types of cancer. The primary protein sequence is transformed in connectivity star graph''s TIs that are used by a statistical linear method in order to construct an input-coded multi-target classification model. The best classification model predicted the probability of presence in HBC/HCC cancer for any of these mutated proteins and the results were analysed with two-way joining clustering analysis method (tw-JCA) from STATISTICA (StatSoft.Inc., 2002). This study is proposing two cancer/non-cancer input-coded multi-target classification models for HBC and HCC using the star network TIs of the protein amino acid sequences. abstract: Abstract The cancer diagnostic is a complex process and, sometimes, the specific markers can interfere or produce negative results. Thus, new simple and fast theoretical models are required. One option is the complex network graphs theory that permits us to describe any real system, from the small molecules to the complex genetic, neural or social networks by transforming real properties in topological indices. This work converts the protein primary structure data in specific Randic's star networks topological indices using the new sequence to star networks (S2SNet) application. A set of 1054 proteins were selected from previous works and contains proteins related or not with two types of cancer, human breast cancer (HBC) and human colon cancer (HCC). The general discriminant analysis method generates an input-coded multi-target classification model with the training/predicting set accuracies of 90.0% for the forward stepwise model type. In addition, a protein subset was modified by single amino acid mutations with higher log-odds PAM250 values and tested with the new classification if can be related with HBC or HCC. In conclusion, we shown that, using simple input data such is the primary protein sequence and the simples linear analysis, it is possible to obtain accurate classification models that can predict if a new protein related with two types of cancer. These results promote the use of the S2SNet in clinical proteomics. url: https://www.sciencedirect.com/science/article/pii/S0022519308006140 doi: 10.1016/j.jtbi.2008.11.017 id: cord-004719-3stcx0dd author: Mushegian, A. R. title: Cell-to-cell movement of plant viruses: Insights from amino acid sequence comparisons of movement proteins and from analogies with cellular transport systems date: 1993 words: 6347.0 sentences: 280.0 pages: flesch: 44.0 cache: ./cache/cord-004719-3stcx0dd.txt txt: ./txt/cord-004719-3stcx0dd.txt summary: In several groups of positive-strand RNA viruses, the movement function is provided by the proteins encoded by the so-called triple gene block including two putative small membrane-associated proteins and a putative RNA helicase. It is concluded that classification of movement proteins based on comparison of their amino acid sequences does not correlate with the type of genome nucleic acid or with grouping of viruses based on phylogenetic analysis of replicative proteins or with the virus host range. Limited sequence similarities were observed between i) movement proteins of dianthoviruses and the MIP family of cellular integral membrane proteins, and ii) between movement proteins of bromoviruses and cucumoviruses and M1 protein of influenza viruses which is involved in nuclear export of viral ribonucleoproteins. With representative sequences of plant virus genomes from many groups available, efforts were made to identify regions of similarity between known movement proteins and to predict movement functions for uncharacterized ORFs. Early observations made by this approach have been reviewed previously (e.g. abstract: Cell-to-cell movement is a crucial step in plant virus infection. In many viruses, the movement function is secured by specific virus-encoded proteins. Amino acid sequence comparisons of these proteins revealed a vast superfamily containing a conserved sequence motif that may comprise a hydrophobic interaction domain. This superfamily combines proteins of viruses belonging to all principal groups of positive-strand RNA viruses, as well as single-stranded DNA containing geminiviruses, double-stranded DNA-containing pararetroviruses (caulimoviruses and badnaviruses), and tospoviruses that have negative-strand RNA genomes with two ambisense segments. In several groups of positive-strand RNA viruses, the movement function is provided by the proteins encoded by the so-called triple gene block including two putative small membrane-associated proteins and a putative RNA helicase. A distinct type of movement proteins with very high content of proline is found in tymoviruses. It is concluded that classification of movement proteins based on comparison of their amino acid sequences does not correlate with the type of genome nucleic acid or with grouping of viruses based on phylogenetic analysis of replicative proteins or with the virus host range. Recombination between unrelated or distantly related viruses could have played a major role in the evolution of the movement function. Limited sequence similarities were observed between i) movement proteins of dianthoviruses and the MIP family of cellular integral membrane proteins, and ii) between movement proteins of bromoviruses and cucumoviruses and M1 protein of influenza viruses which is involved in nuclear export of viral ribonucleoproteins. It is hypothesized that all movement proteins of plant viruses may mediate hydrophobic interactions between viral and cellular macromolecules. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086723/ doi: 10.1007/bf01313766 id: cord-321762-7kiahjyy author: Nandy, Ashesh title: Chapter 5 The GRANCH Techniques for Analysis of DNA, RNA and Protein Sequences date: 2015-12-31 words: 9780.0 sentences: 392.0 pages: flesch: 46.0 cache: ./cache/cord-321762-7kiahjyy.txt txt: ./txt/cord-321762-7kiahjyy.txt summary: We presented our scheme at the First Indo-US Workshop on Mathematical Chemistry in Shantiniketan, West Bengal, India in 1998 [10] where we reported, as stated in the abstract, that "Geometrisation of macromolecular sequences in the form of a graphical representation provides one … technique where the nucleotides in a gene sequence can be viewed as objects in a 4-dimensional space; the method can be extended, in principle, to include, say proteins, in a 20-dimensional space. This review is a brief introduction to the readers of this new and exciting field of research on graphical representation and numerical characterization (GRANCH) of bio-molecular sequences, based on the talk I presented at the Second Mathematical Chemistry Workshop of the Americas in Bogota, Colombia, in July 2010 [13] . abstract: Abstract: The very rapid growth in molecular sequence data from the daily accretion of large gene and protein sequencing projects have led to issues regarding viewing and analyzing the massive amounts of data. Graphical representation and numerical characterization of DNA, RNA and protein sequences have exhibited great potential to address these concerns. We review here in brief several different formulations of these representations and examples of applications to diverse problems based on what this author had presented at the Second Mathematical Chemistry Workshop of the Americas in Bogota, Colombia in 2010. In particular, we note several insights that were gained from such representations, and the applications to the bio-medicinal field. url: https://api.elsevier.com/content/article/pii/B9781681080536500053 doi: 10.1016/b978-1-68108-053-6.50005-3 id: cord-266481-9afb0yvt author: Naskalska, Antonina title: Membrane Protein of Human Coronavirus NL63 Is Responsible for Interaction with the Adhesion Receptor date: 2019-07-17 words: 5673.0 sentences: 289.0 pages: flesch: 51.0 cache: ./cache/cord-266481-9afb0yvt.txt txt: ./txt/cord-266481-9afb0yvt.txt summary: We have previously shown that the virus uses heparan sulfate proteoglycans (HSPGs) as the initial attachment factors, facilitating viral entry into the cell. However, we recently reported that heparan sulfate (HS) proteoglycans (HSPGs) are required for effective adhesion of the virus to the cell surface and that such an interaction enhances the infection process (12) . To further validate this result, we blocked the virus-ACE2 interaction with anti-ACE2 antibody, which resulted in inhibition of MENS VLP internalization but not adhesion to the cell surface (Fig. 3) . Using flow cytometry, we next investigated whether the adhesion of MEN and MENS VLPs to the cell surface involves interaction with HSPGs, as has been shown for HCoV-NL63. Mapping of the receptor-binding domain and amino acids critical for attachment in the spike protein of avian coronavirus infectious bronchitis virus abstract: Human coronavirus NL63 (HCoV-NL63) is a common respiratory virus that causes moderately severe infections. We have previously shown that the virus uses heparan sulfate proteoglycans (HSPGs) as the initial attachment factors, facilitating viral entry into the cell. In the present study, we show that the membrane protein (M) of HCoV-NL63 mediates this attachment. Using viruslike particles lacking the spike (S) protein, we demonstrate that binding to the cell is not S protein dependent. Furthermore, we mapped the M protein site responsible for the interaction with HSPG and confirmed its relevance using a viable virus. Importantly, in silico analysis of the region responsible for HSPG binding in different clinical isolates and the Amsterdam I strain did not exhibit any signs of cell culture adaptation. IMPORTANCE It is generally accepted that the coronaviral S protein is responsible for viral interaction with a cellular receptor. Here we show that the M protein is also an important player during early stages of HCoV-NL63 infection and that the concerted action of the two proteins (M and S) is a prerequisite for effective infection. We believe that this study broadens the understanding of HCoV-NL63 biology and may also alter the way in which we perceive the first steps of cell infection with the virus. The data presented here may also be important for future research into vaccine or drug development. url: https://doi.org/10.1128/jvi.00355-19 doi: 10.1128/jvi.00355-19 id: cord-319884-d8n0aokl author: Natesan, Mohan title: Protein Microarrays and Biomarkers of Infectious Disease date: 2010-12-16 words: 7088.0 sentences: 359.0 pages: flesch: 36.0 cache: ./cache/cord-319884-d8n0aokl.txt txt: ./txt/cord-319884-d8n0aokl.txt summary: Fluorescencebased detection of protein interactions is similar to gene array methods, and data analysis often employs approaches previously developed for genome and transcription studies. A standard assay for measuring antibody interactions with proteins of the vaccinia proteome microarray was first developed with a pool of therapeutic human sera collected from vaccinia-immune individuals (VIg) and this data was compared to results obtained from individuals vaccinated against smallpox using Dryvax. Results from this study suggested that antibodies from vaccination recognized a small number of proteins shared with pathogenic viral strains, while recovery from infection also involved humoral immunity to antigens uniquely recognized within the monkeypox virus proteome (unpublished data). For example, a protein array produced from the outer membrane proteins of Pseudomonas aeruginosa was constructed [38] to study the immune response in patients, and several antibody-binding antigens were identified by this group as potential diagnostic markers. abstract: Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have been developed for different applications, including abundance-based and function-based methods. Depending on the application, design issues should be considered, such as the need for multiplexing and label or label free detection methods. New developments, challenges, and future demands in infectious disease research will impact the application of protein microarrays for discovery and validation of biomarkers. url: https://doi.org/10.3390/ijms11125165 doi: 10.3390/ijms11125165 id: cord-279629-t1xjy12y author: Nazneen Akhand, Mst Rubaiat title: Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine date: 2020-04-15 words: 6717.0 sentences: 379.0 pages: flesch: 47.0 cache: ./cache/cord-279629-t1xjy12y.txt txt: ./txt/cord-279629-t1xjy12y.txt summary: The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Hence, the study was designed to develop a chimeric recombinant vaccine against COVID-19 by targeting four major structural proteins of the pathogen, while revealing the evolutionary history of different species of coronavirus based on whole genome and protein domain-based phylogeny. Apart from the human coronaviruses, we introduced other coronaviruses which choose different species of bats, whale, turkey, rat, mink, ferret, swine, camel, rabbit, cow and others as host (Supplementary TableDomain analysis of spike protein of coronaviruses reveals that they contain mainly one signature domains namely, coronavirus S2 glycoprotein (IPR002552), which is present in all the candidates. Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in silico approach. abstract: SARS-CoV-2 is known to infect the neurological, respiratory, enteric, and hepatic systems of human and has already become an unprecedented threat to global healthcare system. COVID-19, the most serious public condition caused by SARS-CoV-2 leads the world to an uncertainty alongside thousands of regular death scenes. Unavailability of specific therapeutics or approved vaccine has made the recovery of COVI-19 more troublesome and challenging. The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein (S), membrane protein (M), envelope protein and nucleocapsid protein (N) were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins (S, E, M and N) reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and Normal Mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. The development of preventive measures to combat COVID-19 infections might be aided the present study. However, the in vivo and in vitro validation might be ensured with wet lab trials using model animals for the implementation of the presented data. url: https://doi.org/10.1101/2020.04.15.036285 doi: 10.1101/2020.04.15.036285 id: cord-253466-7gpije5d author: Netherton, Christopher title: A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication date: 2007-08-31 words: 26372.0 sentences: 1363.0 pages: flesch: 45.0 cache: ./cache/cord-253466-7gpije5d.txt txt: ./txt/cord-253466-7gpije5d.txt summary: Significantly, Poliovirus infection causes enrichment of GEFs in membranes containing replicase proteins, and this would provide a mechanism for increasing levels of Arf1-GTP at sites of virus replication. There is evidence that Tobacco mosaic virus also uses the ER as a site of replication because the replicase enzyme and viral RNA are located on the ER of infected cells, and infection causes major changes in ER morphology (Reichel and Beachy, 1998) , including ER aggregation and formation of lamella structures. Even though these viruses infect a diverse range of hosts from different phyla, including vertebrates [poxviruses, African swine fever virus (ASFV)], arthropods (entomopox, ASFV, chloriridoviruses), amphibians and fish (Ranavirus, Megalocytivirus, and Lymphocystivirus genera of the Iridoviridae family), marine algae (phycodnaviruses), and protozoa (mimivirus), they all generate cytoplasmic factories as major sites of virus assembly and replication (illustrated in Fig. 4 ). Formation of DNA replication structures in herpes virus-infected cells requires a viral DNA binding protein abstract: Virus replication can cause extensive rearrangement of host cell cytoskeletal and membrane compartments leading to the “cytopathic effect” that has been the hallmark of virus infection in tissue culture for many years. Recent studies are beginning to redefine these signs of viral infection in terms of specific effects of viruses on cellular processes. In this chapter, these concepts have been illustrated by describing the replication sites produced by many different viruses. In many cases, the cellular rearrangements caused during virus infection lead to the construction of sophisticated platforms in the cell that concentrate replicase proteins, virus genomes, and host proteins required for replication, and thereby increase the efficiency of replication. Interestingly, these same structures, called virus factories, virus inclusions, or virosomes, can recruit host components that are associated with cellular defences against infection and cell stress. It is possible that cellular defence pathways can be subverted by viruses to generate sites of replication. The recruitment of cellular membranes and cytoskeleton to generate virus replication sites can also benefit viruses in other ways. Disruption of cellular membranes can, for example, slow the transport of immunomodulatory proteins to the surface of infected cells and protect against innate and acquired immune responses, and rearrangements to cytoskeleton can facilitate virus release. url: https://www.sciencedirect.com/science/article/pii/S0065352707700040 doi: 10.1016/s0065-3527(07)70004-0 id: cord-276988-bvsz5q6d author: Neu, Carolin T. title: Post-Transcriptional Expression Control in Platelet Biogenesis and Function date: 2020-10-15 words: 11394.0 sentences: 581.0 pages: flesch: 38.0 cache: ./cache/cord-276988-bvsz5q6d.txt txt: ./txt/cord-276988-bvsz5q6d.txt summary: Additionally, we will focus on the currently known concepts of post-transcriptional control mechanisms important for RNA fate within platelets with a special emphasis on RBPs. Blood platelets-the major players in hemostasis-are small anucleate cell fragments with a characteristic discoid shape and a diameter of 1 to 3 µm that originate from megakaryocytes (MKs). The m 7 G cap and poly(A) tail promote mRNA translation and stability, while the UTRs expose sequences for RNA-binding proteins (RBPs) and regulatory sites for microRNA (miRNA)-mediated translational and degradation control [45, [52] [53] [54] . Moreover, RNA-Seq analysis of platelet miRNAs in patients with myocardial infarction revealed nine differentially expressed platelet miRNAs compared to healthy controls, which were released upon platelet aggregation and taken up by endothelial cells via a vesicle-dependent mechanism [80] . Megakaryopoiesis, megakaryocyte maturation, as well as platelet formation, were shown to be highly complex processes that are regulated on multiple levels including epigenetic, transcriptional as well as post-transcriptional gene expression control mechanisms. abstract: Platelets are highly abundant cell fragments of the peripheral blood that originate from megakaryocytes. Beside their well-known role in wound healing and hemostasis, they are emerging mediators of the immune response and implicated in a variety of pathophysiological conditions including cancer. Despite their anucleate nature, they harbor a diverse set of RNAs, which are subject to an active sorting mechanism from megakaryocytes into proplatelets and affect platelet biogenesis and function. However, sorting mechanisms are poorly understood, but RNA-binding proteins (RBPs) have been suggested to play a crucial role. Moreover, RBPs may regulate RNA translation and decay following platelet activation. In concert with other regulators, including microRNAs, long non-coding and circular RNAs, RBPs control multiple steps of the platelet life cycle. In this review, we will highlight the different RNA species within platelets and their impact on megakaryopoiesis, platelet biogenesis and platelet function. Additionally, we will focus on the currently known concepts of post-transcriptional control mechanisms important for RNA fate within platelets with a special emphasis on RBPs. url: https://doi.org/10.3390/ijms21207614 doi: 10.3390/ijms21207614 id: cord-279418-3r1ijafm author: Nevers, Quentin title: Negri bodies and other virus membrane-less replication compartments() date: 2020-08-21 words: 6437.0 sentences: 406.0 pages: flesch: 44.0 cache: ./cache/cord-279418-3r1ijafm.txt txt: ./txt/cord-279418-3r1ijafm.txt summary: We particularly examine the interplay between viral factories and the cellular innate immune response, of which several components also form membrane-less condensates in infected cells. With the rapid identification of cellular membraneless compartments and proteins that undergo LLPS in vitro, a major challenge in the field is to demonstrate unambiguously that a specific structure is indeed a phase-separated liquid body in the cellular context. Until now, only a few specific cellular factors, which directly interact with viral proteins such as the nucleoproteins and phosphoproteins of MNV, have been shown to concentrate in these structures. Upon Infection, Cellular WD Repeat-Containing Protein 5 (WDR5) Localizes to Cytoplasmic Inclusion Bodies and Enhances Measles Virus Replication The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression The Cellular Protein CAD is Recruited into Ebola Virus Inclusion Bodies by the Nucleoprotein NP to Facilitate Genome Replication and Transcription abstract: Viruses reshape the organization of the cell interior to achieve different steps of their cellular cycle. Particularly, viral replication and assembly often take place in viral factories where specific viral and cellular proteins as well as nucleic acids concentrate. Viral factories can be either membrane-delimited or devoid of any cellular membranes. In the latter case, they are referred as membrane-less replication compartments. The most emblematic ones are the Negri bodies, which are inclusion bodies that constitute the hallmark of rabies virus infection. Interestingly, Negri bodies and several other viral replication compartments have been shown to arise from a liquid-liquid phase separation process and, thus, constitute a new class of liquid organelles. This is a paradigm shift in the field of virus replication. Here, we review the different aspects of membrane-less virus replication compartments with a focus on the Mononegavirales order and discuss their interactions with the host cell machineries and the cytoskeleton. We particularly examine the interplay between viral factories and the cellular innate immune response, of which several components also form membrane-less condensates in infected cells. url: https://doi.org/10.1016/j.bbamcr.2020.118831 doi: 10.1016/j.bbamcr.2020.118831 id: cord-319722-udqu5jub author: Ng, Eddy W. Y. title: Advances in MALDI Mass Spectrometry in Clinical Diagnostic Applications date: 2013-04-07 words: 12514.0 sentences: 594.0 pages: flesch: 42.0 cache: ./cache/cord-319722-udqu5jub.txt txt: ./txt/cord-319722-udqu5jub.txt summary: One commonly used approach for identification of disease-specific biomarkers is to compare the quantitative biomolecule profiles of plasma/serum specimens from the patients with the target disease and control subjects without the disease. For example, after immunoprecipitation of amyloid-beta peptides from the cerebral spinal fluid, different amyloid-beta isoforms as well as their corresponding stable-isotope labeled internal standards appear as individual peaks of expected m/z values in a MALDI-TOF mass spectrum, and their quantities can be measured with high accuracy with intra-assay CVs <10% [33] . Surface-enhanced laser desorption/ionization TOF mass spectrometry (SELDI-TOF MS) is a variant of MALDI-TOF MS, and is mainly designed for quantitative analysis of proteins in biological samples. It may be because SELDI-TOF MS was the first high-throughput technology that allowed quantitative profiling and comparison of the serum/plasma proteins in a large number of patient samples within a very short period of time. abstract: The concept of matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) was first reported in 1985. Since then, MALDI MS technologies have been evolving, and successfully used in genome, proteome, metabolome, and clinical diagnostic research. These technologies are high-throughput and sensitive. Emerging evidence has shown that they are not only useful in qualitative and quantitative analyses of proteins, but also of other types of biomolecules, such as DNA, glycans, and metabolites. Recently, parallel fragmentation monitoring (PFM), which is a method comparable to selected reaction monitoring, has been reported. This highlights the potentials of MALDI-TOF/TOF tandem MS in quantification of metabolites. Here we critically review the applications of the major MALDI MS technologies, including MALDI-TOF MS, MALDI-TOF/TOF MS, SALDI-TOF MS, MALDI-QqQ MS, and SELDI-TOF MS, to the discovery and quantification of disease biomarkers in biological specimens, especially those in plasma/serum specimens. Using SELDI-TOF MS as an example, the presence of systemic bias in biomarker discovery studies employing MALDI-TOF MS and its possible solutions are also discussed in this chapter. The concepts of MALDI, SALDI, SELDI, and PFM are complementary to each other. Theoretically, all these technologies can be combined, leading to the next generation of the MALDI MS technologies. Real applications of MALDI MS technologies in clinical diagnostics should be forthcoming. url: https://www.ncbi.nlm.nih.gov/pubmed/23563502/ doi: 10.1007/128_2012_413 id: cord-255371-o9oxchq6 author: Nguyen, Thanh Thi title: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) date: 2020-07-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that has caused the global COVID-19 pandemic. Tracing the evolution and transmission of the virus is crucial to respond to and control the pandemic through appropriate intervention strategies. This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. Prediction results suggest that mutation D614G in the virus spike protein, which has attracted much attention from researchers, is unlikely to make changes in protein secondary structure and relative solvent accessibility. Based on 6,324 viral genome sequences, we create a spreadsheet dataset of point mutations that can facilitate the investigation of SARS-CoV-2 in many perspectives, especially in tracing the evolution and worldwide spread of the virus. Our analysis results also show that coding genes E, M, ORF6, ORF7a, ORF7b and ORF10 are most stable, potentially suitable to be targeted for vaccine and drug development. url: https://doi.org/10.1101/2020.07.10.171769 doi: 10.1101/2020.07.10.171769 id: cord-282604-xp71rkxc author: Nikolaev, EN title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein date: 2020-05-25 words: 2181.0 sentences: 114.0 pages: flesch: 53.0 cache: ./cache/cord-282604-xp71rkxc.txt txt: ./txt/cord-282604-xp71rkxc.txt summary: title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein We have developed a mass-spectrometry based method for the detection of the SARS CoV-2 virus in nasopharynx epithelial swabs, based on the detection of the viral nucleocapsid N protein. The N protein of the SARS-COV-2 virus, the most abundant protein in the virion, is the best candidate for mass-spectrometric detection of the infection, and MS-based detection of several peptides from the SARS-COoV-2 nucleoprotein has been reported earlier by the Sinz group [4]. We have performed a pilot study on nasopharynx epithelial swabs already collected from patients with CODIV-19 for RT-qPCR and showed confident identification of the N protein of the SARS CoV-2 virus by mass-spectrometry with the use of a very basic sample preparation procedure. Mass Spectrometric Identification of SARS-CoV-2 Proteins from Gargle Solution Samples of COVID-19 Patients abstract: Detection of viral RNA by PCR is currently the main diagnostic tool for COVID-19 [1]. The PCR-based test, however, shows limited sensitivity, especially at early and late stages of the disease development [2,3], and is relatively time consuming. Fast and reliable complementary methods for detecting the viral infection would be of help in the current pandemia conditions. Mass-spectrometry is one of such possibilities. We have developed a mass-spectrometry based method for the detection of the SARS CoV-2 virus in nasopharynx epithelial swabs, based on the detection of the viral nucleocapsid N protein. The N protein of the SARS-COV-2 virus, the most abundant protein in the virion, is the best candidate for mass-spectrometric detection of the infection, and MS-based detection of several peptides from the SARS-COoV-2 nucleoprotein has been reported earlier by the Sinz group [4]. Our approach shows confident identification of the N protein in patient samples even with the lowest viral loads and a much simpler preparation procedure. Our main protocol consists of virus inactivation by heating and adding of isopropanol, and tryptic digestion of the proteins sedimented from the swabs followed by MS analysis. A set of unique peptides, produced as a result of proteolysis of the nucleocapsid phosphoprotein of SARS-CoV-2, is detected. The obtained results can further be used to create fast parallel mass-spectrometric approaches for the detection of the virus in the nasopharyngeal mucosa, saliva, sputum and other physiological fluids. url: https://doi.org/10.1101/2020.05.24.113043 doi: 10.1101/2020.05.24.113043 id: cord-336119-8g37xsys author: Nimgampalle, Mallikarjuna title: Screening of Chloroquine, Hydroxychloroquine and its derivatives for their binding affinity to multiple SARS-CoV-2 protein drug targets date: 2020-06-24 words: 5464.0 sentences: 283.0 pages: flesch: 50.0 cache: ./cache/cord-336119-8g37xsys.txt txt: ./txt/cord-336119-8g37xsys.txt summary: Our current study also shows that some of the chemically synthesized Chloroquine derivatives can also potentially inhibit various SARS-CoV-2 viral proteins by binding to them and concomitantly effectively disrupting the active site of these proteins. By using in-silico molecular docking studies, the binding potential of Chloroquine and its derivatives with different SARS-CoV-2 proteins involved in viral replication was evaluated. Based on the recent reports, some of the essential regulatory proteins and enzymes associated with the pathogenesis of SARS-CoV-2 were selected as drug targets such as the Spike glycoprotein that enables virus internalization, RNA dependent RNA polymerase that supports replication of viral genetic material, Chimeric RBD (Receptor binding domain) that interacts with the ACE 2, Main protease responsible for cleaving the viral polypeptide, Non-structural Protein3, Nonstructural Protein 10, Non-structural Protein 9 (Replicase Table 3 . abstract: Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities’ world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time screening was performed for some chemically synthesized derivatives of Chloroquine and compared their binding efficacy with chemically synthesized Chloroquine derivatives through in silico approaches. For the purpose of the study, some essential viral proteins and enzymes were selected that are implicated in SARS-CoV-2 replication and multiplication as putative drug targets. Chloroquine, Hydroxychloroquine, and some of their chemically synthesized derivatives, taken from earlier published studies were selected as drug molecules. We have conducted molecular docking and related studies between Chloroquine and its derivatives and SARS-CoV-2 viral proteins, and the findings show that both Chloroquine and Hydroxychloroquine can bind to specific structural and non-structural proteins implicated in the pathogenesis of SARS-CoV-2 infection with different efficiencies. Our current study also shows that some of the chemically synthesized Chloroquine derivatives can also potentially inhibit various SARS-CoV-2 viral proteins by binding to them and concomitantly effectively disrupting the active site of these proteins. These findings bring into light another possible mechanism of action of Chloroquine and Hydroxychloroquine and also pave the way for further drug repurposing and remodeling. Communicated by Ramaswamy H. Sarma url: https://doi.org/10.1080/07391102.2020.1782265 doi: 10.1080/07391102.2020.1782265 id: cord-324667-wmhdw1qs author: Nishtala, Krishnatej title: Tear biomarkers for keratoconus date: 2016-08-04 words: 4082.0 sentences: 226.0 pages: flesch: 36.0 cache: ./cache/cord-324667-wmhdw1qs.txt txt: ./txt/cord-324667-wmhdw1qs.txt summary: Advances in technologies such as mass spectrometry and NMR have helped in studying and understanding molecular changes in the tear proteome, lipidome and metabolome relating to an ocular disease condition. Enzyme linked immunosorbent assay (ELISA) analysis of capillary collected tears in 28 [61] , 30 [62] and 94 [63] patients with keratoconus in three different studies showed elevated levels of inflammatory markers IL-6, TNFα and MMP9. Protein levels of gross cystic disease fluid protein-15/ prolactin-inducible protein (PIP) and zinc-alpha-2glycoprotein have been found to be elevated in tears of 36 patients by proteomic analysis, suggesting their application as prognostic markers for keratoconus [72] ( Table 2 ). A multi-omics approach integrating data from proteomics, lipidomics and metabolomics is the need of the hour for studying tear fluid as an important source of biomarkers in keratoconus to lead to effective prognosis and treatment of the disease. abstract: Keratoconus is a progressive corneal thinning, ectatic condition, which affects vision. Recent advances in corneal topography measurements has helped advance proper diagnosis of this condition and increased research and clinical interests in the disease etiopathogenesis. Considerable progress has been achieved in understanding the progression of the disease and tear fluid has played a major role in the progress. This review discusses the importance of tear fluid as a source of biomarker for keratoconus and how advances in technology have helped map the complexity of tears and thereby molecular readouts of the disease. Expanding knowledge of the tear proteome, lipidome and metabolome opened up new avenues to study keratoconus and to identify probable prognostic or diagnostic biomarkers for the disease. A multidimensional approach of analyzing tear fluid of patients layering on proteomics, lipidomics and metabolomics is necessary in effectively decoding keratoconus and thereby identifying targets for its treatment. url: https://doi.org/10.1186/s40662-016-0051-9 doi: 10.1186/s40662-016-0051-9 id: cord-314751-i9rxesrg author: Oh, Jongsuk title: Immunogenicity and protective efficacy of recombinant S1 domain of the porcine epidemic diarrhea virus spike protein date: 2014-07-10 words: 6006.0 sentences: 242.0 pages: flesch: 44.0 cache: ./cache/cord-314751-i9rxesrg.txt txt: ./txt/cord-314751-i9rxesrg.txt summary: In this study, a codon-optimized PEDV S1 gene containing amino acid residues 25–738 was synthesized based on a multiple alignment of the S amino acid sequences of PEDV field isolates and used to establish a stable porcine cell line constitutively expressing the PEDV S1 protein. In the present study, therefore, we first synthesized a full-length, codon-optimized PEDV S1 gene and then generated a stable porcine-origin cell line constitutively expressing the recombinant S1 protein. These results were coincident with the rabbit study described above, since the rabbit antisera generated by immunization with the recombinant S1 protein also contained low levels of neutralizing antibodies to the heterologous PEDV vaccine strain. In the present study, the first aim was to stably express the full-length, codon-optimized S1 gene of PEDV in porcine-origin cells and to evaluate the immunogenicity and efficacy of the recombinant S1 protein. abstract: Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine. Acute PEDV outbreaks have continually emerged in most swine-producing Asian countries and, recently, in the United States, causing significant economic losses in the pig industry. The spike (S) protein of PEDV is a type 1 transmembrane envelope glycoprotein and consists of the S1 and S2 domains, which are responsible for virus binding and fusion, respectively. Since the S1 domain is involved in a specific high-affinity interaction with the cellular receptor and induction of neutralizing antibody in the natural host, it is a primary target for the development of effective vaccines against PEDV. In this study, a codon-optimized PEDV S1 gene containing amino acid residues 25–738 was synthesized based on a multiple alignment of the S amino acid sequences of PEDV field isolates and used to establish a stable porcine cell line constitutively expressing the PEDV S1 protein. The purified recombinant S1 protein was found to mediate highly potent antibody responses in immunized rabbits. The antibodies strongly recognized the recombinant S1 protein from cell lysates and supernatants of S1-expressing cells, whereas they bound weakly to the authentic S protein of PEDV vaccine strain SM98-1. Furthermore, a serum neutralization test revealed that the rabbit antisera completely inhibit infection of the PEDV vaccine strain at a serum dilution of 1:16. We then tested the ability of vaccination with the recombinant S1 protein to protect piglets against PEDV. Late-term pregnant sows were inoculated intramuscularly with the purified S1 protein, and the outcome was investigated in passively immunized suckling piglets after a virulent PEDV challenge. The results showed that vaccination with S1 protein efficiently protected neonatal piglets against PEDV. Our data suggest that the recombinant S1 protein shows potential as an effective and safe subunit vaccine for PED prevention. url: https://www.ncbi.nlm.nih.gov/pubmed/25008896/ doi: 10.1007/s00705-014-2163-7 id: cord-023740-g84fa45m author: Oldstone, Michael B.A. title: Mimicry by Virus of Host Molecules: Implications for Autoimmune Disease date: 2014-06-27 words: 2498.0 sentences: 117.0 pages: flesch: 41.0 cache: ./cache/cord-023740-g84fa45m.txt txt: ./txt/cord-023740-g84fa45m.txt summary: Monoclonal antibodies against 11 different viruses including DNA and RNA viruses known to cause human infection from the herpes virus group, vaccinia virus, myxoviruses, paramyxoviruses, arenaviruses, flaviviruses, alphaviruses, rhabdovirus, and coronaviruses cross-react with host cell determinants expressed on uninfected tissues. other examples (reviewed in Oldstone and Notkins, 1986 ) suggest a mechanism whereby immune reactants directed against a viral or microbial component may cross-react with a host component and generate autoimmune disease. Since, on the basis of antibody cross-reactivity, many viruses share antigenic sites with normal host cell components, the next step was to look for crossreactive capability in eliciting autoimmunity and related disease. The most likely mechanism by which molecular mimicry would cause disease is by eliciting an immune response against a determinant shared between the host and the virus to bring forth a tissue-specific immune response, presumably capable of destroying cells and eventually the tissue. abstract: Molecular mimicry defines the shared identity of molecules from disparate genes or proteins. Thus, although their origins are as separate as a virus and the self-determinant of a human or lower animal, two molecules' linear amino acid sequences or their conformational fits may be shared. Such molecular homologies between proteins occur frequently and likely play roles in the processing of viral proteins inside cells. The homologies shared between viruses and host cytoskeletal proteins likely indicate that shared determinants on cell linker proteins guided viral proteins along highways and stop points inside cells. Most importantly, these unexpected cross-reactivities have broad and major implications for understanding autoimmune disease. Molecular mimicry is detected either by using humoral or cellular immune components, that cross-react with two presumably unrelated protein structures, or by computer searches to match descriptions of proteins in storage banks. The use of both these approaches to define molecular mimicry and establish its potential role in autoimmune disease is the topic of this chapter. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173565/ doi: 10.1016/b978-0-12-174685-8.50079-2 id: cord-004435-l66ost6q author: Oli, Angus Nnamdi title: Immunoinformatics and Vaccine Development: An Overview date: 2020-02-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The use of vaccines have resulted in a remarkable improvement in global health. It has saved several lives, reduced treatment costs and raised the quality of animal and human lives. Current traditional vaccines came empirically with either vague or completely no knowledge of how they modulate our immune system. Even at the face of potential vaccine design advance, immune-related concerns (as seen with specific vulnerable populations, cases of emerging/re-emerging infectious disease, pathogens with complex lifecycle and antigenic variability, need for personalized vaccinations, and concerns for vaccines' immunological safety -specifically vaccine likelihood to trigger non-antigen-specific responses that may cause autoimmunity and vaccine allergy) are being raised. And these concerns have driven immunologists toward research for a better approach to vaccine design that will consider these challenges. Currently, immunoinformatics has paved the way for a better understanding of some infectious disease pathogenesis, diagnosis, immune system response and computational vaccinology. The importance of this immunoinformatics in the study of infectious diseases is diverse in terms of computational approaches used, but is united by common qualities related to host–pathogen relationship. Bioinformatics methods are also used to assign functions to uncharacterized genes which can be targeted as a candidate in vaccine design and can be a better approach toward the inclusion of women that are pregnant into vaccine trials and programs. The essence of this review is to give insight into the need to focus on novel computational, experimental and computation-driven experimental approaches for studying of host–pathogen interactions and thus making a case for its use in vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049754/ doi: 10.2147/itt.s241064 id: cord-332948-h297ukuu author: Olotu, Fisayo A. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. date: 2020-10-16 words: 5176.0 sentences: 315.0 pages: flesch: 51.0 cache: ./cache/cord-332948-h297ukuu.txt txt: ./txt/cord-332948-h297ukuu.txt summary: authors: Olotu, Fisayo A.; Omolabi, Kehinde F.; Soliman, Mahmoud E.S. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. 30 Identification of other functional (allosteric) sites on the prefusion S protein could present another dynamic and effective approach of preventing SARS-CoV-2 infectivity relative to its interaction with the host cell ACE2 and proteases. 53 Relatively, this study was implemented to (i) identify potential druggable sites across the S1 and S2 domains of the SARS-CoV-2 S protein other than the RBD-hACE2 interface (ii) perform high-throughput (virtual) screening of ~1500 FDA approved drugs against the most druggable site(s) (iii) investigate the binding dynamics and interaction mechanisms of the compounds and their consequential effects on the S-protein RBD-ACE2 complex. We believe this systematic study will be able to provide structural and molecular insights into possible allosteric sites on SARS-CoV-2 S protein suitable for selective targeting and structureComputational methodologies abstract: The systematic entry of SARS-CoV-2 into host cells, as mediated by its Spike (S) protein, is highly essential for pathogenicity in humans. Hence, targeting the viral entry mechanisms remains a major strategy for COVID-19 treatment. Although recent efforts have focused on the direct inhibition of S-protein receptor-binding domain (RBD) interactions with human angiotensin-converting enzyme 2 (hACE2), allosteric targeting remains an unexplored possibility. Therefore, in this study, for the first time, we employed an integrative meta-analytical approach to investigate the allosteric inhibitory mechanisms of SARS-CoV-2 S-protein and its association with hACE2. Findings revealed two druggable sites (Sites 1 and 2) located at the N-terminal domain (NTD) and S2 regions of the protein. Two high-affinity binders; ZINC3939013 (Fosaprepitant – Site 1) and ZINC27990463 (Lomitapide – Site 2) were discovered via site-directed high-throughput screening against a library of ∼1500 FDA approved drugs. Interestingly, we observed that allosteric binding of both compounds perturbed the prefusion S-protein conformations, which in turn, resulted in unprecedented hACE2 displacement from the RBD. Estimated ΔG(binds) for both compounds were highly favorable due to high-affinity interactions at the target sites. In addition, Site 1 residues; R190, H207, K206 and K187, I101, R102, I119, F192, L226, V126 and W104 were identified for their crucial involvement in the binding and stability of ZINC3939013. Likewise, energy contributions of Q957, N953, Q954, L303, Y313, Q314, L858, V952, N953, and A956 corroborated their importance to ZINC27990463 binding at the predicted Site 2. We believe these findings would pave way for the structure-based discovery of allosteric SARS-CoV-2 S-protein inhibitors for COVID-19 treatment. url: https://api.elsevier.com/content/article/pii/S2352914820306018 doi: 10.1016/j.imu.2020.100451 id: cord-262119-s6hc7fxs author: Ostaszewski, Marek title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date: 2020-10-27 words: 12332.0 sentences: 742.0 pages: flesch: 38.0 cache: ./cache/cord-262119-s6hc7fxs.txt txt: ./txt/cord-262119-s6hc7fxs.txt summary: title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms The molecular pathophysiology that links SARS-CoV-2 infection to the clinical manifestations and course of COVID-19 is complex and spans multiple biological pathways, cell types and organs [2, 3] . With this goal in mind, we initiated a collaborative effort involving over 230 biocurators, domain experts, modelers and data analysts from 120 institutions in 30 countries to develop the COVID-19 Disease Map, an open-access collection of curated computational diagrams and models of molecular mechanisms implicated in the disease [4] . The COVID-19 Disease Map diagrams, available in layout-aware systems biology formats and integrated with external repositories, are available in several formats allowing a range of computational analyses, including network analysis and Boolean, kinetic or multiscale simulations. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms abstract: We hereby describe a large-scale community effort to build an open-access, interoperable, and computable repository of COVID-19 molecular mechanisms - the COVID-19 Disease Map. We discuss the tools, platforms, and guidelines necessary for the distributed development of its contents by a multi-faceted community of biocurators, domain experts, bioinformaticians, and computational biologists. We highlight the role of relevant databases and text mining approaches in enrichment and validation of the curated mechanisms. We describe the contents of the map and their relevance to the molecular pathophysiology of COVID-19 and the analytical and computational modelling approaches that can be applied to the contents of the COVID-19 Disease Map for mechanistic data interpretation and predictions. We conclude by demonstrating concrete applications of our work through several use cases. url: https://doi.org/10.1101/2020.10.26.356014 doi: 10.1101/2020.10.26.356014 id: cord-017887-pj6pal35 author: OuYang, Bo title: Structural and Functional Properties of Viral Membrane Proteins date: 2018-06-29 words: 11512.0 sentences: 560.0 pages: flesch: 48.0 cache: ./cache/cord-017887-pj6pal35.txt txt: ./txt/cord-017887-pj6pal35.txt summary: Functional mutagenesis studies have suggested that, at least in the cases of HIV-1 and influenza A viruses, the TM domains (TMDs) of fusion proteins are not merely membrane anchors, but play important roles in membrane fusion and viral infectivity. Apart from the channels and fusion proteins, some viruses have developed enzymatic domains anchored to the membrane, e.g., the polymerases of the hepatitis C virus and the neurominidase of the influenza viruses. Unlike many other broad-spectrum antivirals, Arbidol has an established mechanism of action against the HAs in influenza A and B viruses that involves the inhibition of virus-mediated membrane fusion and thus viral entry [50] . The NMR structure of the HIV-1 Env TMD may provide some clues for how other viral fusion proteins oligomerize in the membrane. Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes abstract: Viruses have developed a large variety of transmembrane proteins to carry out their infectious cycles. Some of these proteins are simply anchored to membrane via transmembrane helices. Others, however, adopt more interesting structures to perform tasks such as mediating membrane fusion and forming ion-permeating channels. Due to the dynamic or plastic nature shown by many of the viral membrane proteins, structural and mechanistic understanding of these proteins has lagged behind their counterparts in prokaryotes and eukaryotes. This chapter provides an overview of the use of NMR spectroscopy to unveil the transmembrane and membrane-proximal regions of viral membrane proteins, as well as their interactions with potential therapeutics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122571/ doi: 10.1007/978-981-13-0532-0_6 id: cord-345712-gmzue6lj author: Palazzo, Luca title: ADP‐ribosylation: new facets of an ancient modification date: 2017-04-26 words: 6641.0 sentences: 389.0 pages: flesch: 42.0 cache: ./cache/cord-345712-gmzue6lj.txt txt: ./txt/cord-345712-gmzue6lj.txt summary: Altogether, ADPribosylation is a widespread modification that controls a vast number of cellular processes, including DNA damage repair, transcription, cell-cycle progression, cell division, unfolded protein response, aging, nitrogen fixation, microbial pathogenicity, cell death and many others [7, 14, [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] . As a consequence, macrodomain-containing proteins are involved in a diverse set of cellular functions, such as chromatin remodelling and DNA-damage repair, oxidative stress response, metabolic processes and pathogenic mechanisms [3,5,10-13,30,37, 53, 54, [59] [60] [61] . Studies looking either at the genomic context of ADPribosylating systems or their evolution in bacteria suggest that ADP-ribosylation might be involved in the regulation of many crucial cellular processes including bacterial persistence, oxidative stress response and adaptation to the host environment in general [5, 9, 49, 154] . abstract: Rapid response to environmental changes is achieved by uni‐ and multicellular organisms through a series of molecular events, often involving modification of macromolecules, including proteins, nucleic acids and lipids. Amongst these, ADP‐ribosylation is of emerging interest because of its ability to modify different macromolecules in the cells, and its association with many key biological processes, such as DNA‐damage repair, DNA replication, transcription, cell division, signal transduction, stress and infection responses, microbial pathogenicity and aging. In this review, we provide an update on novel pathways and mechanisms regulated by ADP‐ribosylation in organisms coming from all kingdoms of life. url: https://doi.org/10.1111/febs.14078 doi: 10.1111/febs.14078 id: cord-310947-aqau2n7q author: Pan, Ji''An title: Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication date: 2008-10-01 words: 6821.0 sentences: 302.0 pages: flesch: 43.0 cache: ./cache/cord-310947-aqau2n7q.txt txt: ./txt/cord-310947-aqau2n7q.txt summary: In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. However, the viral protein interaction maps have been generated until now only for a limited number of viruses, including T7 bacteriophage [1] , vaccinia virus [2] , potato virus A [3] , pea seed-borne mosaic virus [3] , wheat steak mosaic virus [4] , hepatitis C virus [5, 6] , porcine teschovirus [7] , Kaposi sarcoma-associated herpesvirus [8] , and very recently severe acute respiratory syndrome coronavirus (SARS-CoV) [9, 10] . abstract: Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp) 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins. url: https://www.ncbi.nlm.nih.gov/pubmed/18827877/ doi: 10.1371/journal.pone.0003299 id: cord-260057-2m6jdvtc author: Pandey, Preeti title: Insights into the biased activity of dextromethorphan and haloperidol towards SARS-CoV-2 NSP6: in silico binding mechanistic analysis date: 2020-09-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: ABSTRACT: The outbreak of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus continually led to infect a large population worldwide. SARS-CoV-2 utilizes its NSP6 and Orf9c proteins to interact with sigma receptors that are implicated in lipid remodeling and ER stress response, to infect cells. The drugs targeting the sigma receptors, sigma-1 and sigma-2, have emerged as effective candidates to reduce viral infectivity, and some of them are in clinical trials against COVID-19. The antipsychotic drug, haloperidol, exerts remarkable antiviral activity, but, at the same time, the sigma-1 benzomorphan agonist, dextromethorphan, showed pro-viral activity. To explore the potential mechanisms of biased binding and activity of the two drugs, haloperidol and dextromethorphan towards NSP6, we herein utilized molecular docking–based molecular dynamics simulation studies. Our extensive analysis of the protein-drug interactions, structural and conformational dynamics, residual frustrations, and molecular switches of NSP6-drug complexes indicates that dextromethorphan binding leads to structural destabilization and increase in conformational dynamics and energetic frustrations. On the other hand, the strong binding of haloperidol leads to minimal structural and dynamical perturbations to NSP6. Thus, the structural insights of stronger binding affinity and favorable molecular interactions of haloperidol towards viral NSP6 suggests that haloperidol can be potentially explored as a candidate drug against COVID-19. KEY MESSAGES: •Inhibitors of sigma receptors are considered as potent drugs against COVID-19. •Antipsychotic drug, haloperidol, binds strongly to NSP6 and induces the minimal changes in structure and dynamics of NSP6. •Dextromethorphan, agonist of sigma receptors, binding leads to overall destabilization of NSP6. •These two drugs bind with NSP6 differently and also induce differences in the structural and conformational changes that explain their different mechanisms of action. •Haloperidol can be explored as a candidate drug against COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00109-020-01980-1) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/32965508/ doi: 10.1007/s00109-020-01980-1 id: cord-002842-4evbeijx author: Pandey, Rajan Kumar title: Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein date: 2018-01-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response. This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity, allergenicity and physiochemical parameters. To enhance the stability of vaccine protein, disulfide engineering was performed in a region of high mobility. Codon adaptation and in silico cloning was also performed to ensure the higher expression of designed subunit vaccine in E. coli K12 expression system. Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability. Moreover, the designed subunit vaccine was found to induce anti-salivary immunity which may have the ability to prevent the entry of Plasmodium sporozoites into the human host. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773588/ doi: 10.1038/s41598-018-19456-1 id: cord-009792-e2vvi8qo author: Pandit, SB title: Structural and Functional Characterization of Gene Products Encoded in the Human Genome by Homology Detection date: 2008-01-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Availability of the human genome data has enabled the exploration of a huge amount of biological information encoded in it. There are extensive ongoing experimental efforts to understand the biological functions of the gene products encoded in the human genome. However, computational analysis can aid immensely in the interpretation of biological function by associating known functional/structural domains to the human proteins. In this article we have discussed the implications of such associations. The association of structural domains to human proteins could help in prioritizing the targets for structure determination in the structural genomics initiatives. The protein kinase family is one of the most frequently occurring protein domain families in the human proteome while P‐loop hydrolase, which comprises many GTPases and ATPases, is a highly represented superfamily. Using the superfamily relationships between families of unknown and known structures we could increase structural information content of the human genome by about 5%. We could also make new associations of domain families to 33 human proteins that are potentially linked to genetically inherited diseases. IUBMB Life, 56: 317‐331, 2004 url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165581/ doi: 10.1080/15216540400006105 id: cord-304607-td0776wj author: Paszkiewicz, Konrad H. title: Omics, Bioinformatics, and Infectious Disease Research date: 2010-12-24 words: 7022.0 sentences: 367.0 pages: flesch: 46.0 cache: ./cache/cord-304607-td0776wj.txt txt: ./txt/cord-304607-td0776wj.txt summary: This chapter discusses the current state of play of bioinformatics related to genomics and transcriptomics, briefs metagenomics that finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms. Bioinformatics plays a key role at several steps in genomics, comparative genomics, and functional genomics: sequence alignment, assembly, identification of single nucleotide polymorphisms (SNP), gene prediction, quantitative analysis of transcription data, etc. The term "metagenomics" was originally used to describe the sequencing of genomes of uncultured microorganisms in order to explore their abilities to produce natural products (Handelsman et al., 1998 , Rondon et al., 2000 and subsequently resulted in novel insights into the ecology and evolution of microorganisms on a scale not imagined possible before (see Cardenas and Tiedje, 2008; Hugenholtz and Tyson, 2008 for an overview). However, metagenomics now finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms from, for example, patient material that could lead to the identification of the cause of disease. abstract: Bioinformatics is basically the study of informatic processes in biotic systems. Actually what constitutes bioinformatics is not entirely clear and arguably varies depending on who tries to define it. This chapter discusses the considerable progress in infectious diseases research that has been made in recent years using various “omics” case studies. Bioinformatics is tasked with making sense of it, mining it, storing it, disseminating it, and ensuring valid biological conclusions can be drawn from it. This chapter discusses the current state of play of bioinformatics related to genomics and transcriptomics, briefs metagenomics that finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms. This chapter explains the various possibilities of pan-genome, transcriptional reshaping and also enormous progress of proteomics study. Bioinformatic algorithms and tools are crucial tools in analyzing the data. The chapter also attempts to provide some details on the various problems and solution in bioinformatics that current-day scientists face while concentrating on second-generation sequencing strategies. url: https://api.elsevier.com/content/article/pii/B9780123848901000182 doi: 10.1016/b978-0-12-384890-1.00018-2 id: cord-011184-ohdukhqt author: Patil, Shital P. title: Plant-Derived Bioactive Peptides: A Treatment to Cure Diabetes date: 2019-07-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: ABSTRACT: Recent advances in analytical techniques have opened new opportunities for plant-based drug discovery in the field of peptide and proteins. Enzymatic hydrolysis of plant parent proteins forms bioactive peptides which are explored in the treatment of various diseases. In this review, we will discuss the identified plant-based bioactive proteins and peptides and the in vitro, in vivo results for the treatment of diabetes. Extraction, isolation, characterization and commercial utilization of plant proteins is a challenge for the pharmaceutical industry as plants contain several interfering secondary metabolites. The market of peptide drugs for the treatment of diabetes is growing at a fast rate. Plant-based bioactive peptides might open up new opportunities to discover economic lead for the management of various diseases. GRAPHIC ABSTRACT: [Image: see text] url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223764/ doi: 10.1007/s10989-019-09899-z id: cord-010938-12igesqw author: Patra, Prasanta title: Epitope-Based Vaccine Designing of Nocardia asteroides Targeting the Virulence Factor Mce-Family Protein by Immunoinformatics Approach date: 2019-08-21 words: 4628.0 sentences: 284.0 pages: flesch: 47.0 cache: ./cache/cord-010938-12igesqw.txt txt: ./txt/cord-010938-12igesqw.txt summary: title: Epitope-Based Vaccine Designing of Nocardia asteroides Targeting the Virulence Factor Mce-Family Protein by Immunoinformatics Approach Appropriate structural identity of the virulence factor Mce-family protein generated through Phyre2 server and subsequently validated by ProSA and PROCHECK program suite. Consequently the targeted protein sequence has been crucially analyzed through several authentic web prediction portals focus to extract the functional epitopes leading to narrative vaccine generation against Nocardiosis disease. The server utilizes recurrent neural network technique to locate the specific B-cell epitopes present in targeted protein sequence. Amino acid sequence of virulence factor Mce-family protein has been submitted to the server and a zip file containing predictions is comes out as systematic result component. ABCpred server predicts 20 linear epitopes (Table 1) within the virulence factor Mce-family protein of 20 amino The structural profile of virulence factor Mce family protein also been mapped out via Phyre2 server that will be fundamental for therapeutics to design the vaccine. abstract: Nocardia asteroides is the main causative agent responsible for nocardiosis disease in immunocompromised patient viz. Acquired Immunodeficiency Syndrome (AIDS), malignancy, diabetic, organ recipient and genetic disorders. The virulence factor and outer membrane protein pertains immense contribution towards the designing of epitopic vaccine and limiting the robust outbreak of diseases. While epitopic based vaccine element carrying B and T cell epitope along with adjuvant is highly immunoprophylactic in nature. Present research equips immunoinformatics to figure out the suitable epitopes for effective vaccine designing. The selected epitopes VLGSSVQTA, VNIELKPEF and VVPSNLFAV amino acids sequence are identified by HLA-DRB alleles of both MHC class (MHC-I and II) molecules. Simultaneously, these also accessible to B-cell, confirmed through the ABCPred server. Antigenic property expression is validated by the Vaxijen antigenic prediction web portal. Molecular docking between the epitopes and T cell receptor delta chain authenticate the accurate interaction between epitope and receptor with significantly low binding energy. Easy access of epitopes to immune system also be concluded as transmembrane nature of the protein verified by using of TMHMM server. Appropriate structural identity of the virulence factor Mce-family protein generated through Phyre2 server and subsequently validated by ProSA and PROCHECK program suite. The structural configuration of theses epitopes also shaped using DISTILL web server. Both the structure of epitopes and protein will contribute a significant step in designing of epitopic vaccine against N. asteroides. Therefore, such immunoinformatics based computational drive definitely provides a conspicuous impel towards the development of epitopic vaccine as a promising remedy of nocardiosis url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223102/ doi: 10.1007/s10989-019-09921-4 id: cord-266617-z8uecyl6 author: Pavesi, Angelo title: Asymmetric evolution in viral overlapping genes is a source of selective protein adaptation date: 2019-04-03 words: 6677.0 sentences: 326.0 pages: flesch: 52.0 cache: ./cache/cord-266617-z8uecyl6.txt txt: ./txt/cord-266617-z8uecyl6.txt summary: Analysis of nucleotide and amino acid sequences revealed that half of overlaps undergo asymmetric evolution, as the protein from one frame shows a number of substitutions significantly higher than that of the protein from the other frame. I classified a pair of homologous overlaps as a case of symmetric evolution, if the number of amino acid substitutions in the Up1-Up2 alignment did not significantly differ from that in the Down1-Down2 alignment (chi-square < 3.84). In alternative, I classified a pair of homologous overlaps as a case of asymmetric evolution, if the number of amino acid substitutions in the Up1-Up2 alignment was significantly different from that in the Down1-Down2 alignment (chi-square > 3.84). The analysis of the pattern of nucleotide substitutions in the 75 pairs of homologous overlaps revealed 39 and 36 cases of symmetric and asymmetric evolution, respectively (Supplementary Table S2 ). abstract: Overlapping genes represent an intriguing puzzle, as they encode two proteins whose ability to evolve is constrained by each other. Overlapping genes can undergo “symmetric evolution” (similar selection pressures on the two proteins) or “asymmetric evolution” (significantly different selection pressures on the two proteins). By sequence analysis of 75 pairs of homologous viral overlapping genes, I evaluated their accordance with one or the other model. Analysis of nucleotide and amino acid sequences revealed that half of overlaps undergo asymmetric evolution, as the protein from one frame shows a number of substitutions significantly higher than that of the protein from the other frame. Interestingly, the most variable protein (often known to interact with the host proteins) appeared to be encoded by the de novo frame in all cases examined. These findings suggest that overlapping genes, besides to increase the coding ability of viruses, are also a source of selective protein adaptation. url: https://www.sciencedirect.com/science/article/pii/S0042682219300881 doi: 10.1016/j.virol.2019.03.017 id: cord-294712-kvvxmvqo author: Pelosse, Martin title: MultiBac: from protein complex structures to synthetic viral nanosystems date: 2017-10-30 words: 5379.0 sentences: 272.0 pages: flesch: 38.0 cache: ./cache/cord-294712-kvvxmvqo.txt txt: ./txt/cord-294712-kvvxmvqo.txt summary: The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. We then turned our attention to eukaryotic methods, specifically an expression vector system relying on a recombinant baculovirus, to infect insect cell cultures for producing the complexes in which we had interest. This particular feature, and the-at least conceptually-relative ease of manipulating baculovirus in the laboratory by non-expert users, was exciting and led us on to the development of MultiBac: a baculovirus/insect cell system specifically engineered for expressing functional multiprotein complexes in the quality and quantity required for high-resolution structural and mechanistic studies [7] [8] [9] [10] [11] . The introduced genome alterations resulted in a virus that exhibited delayed lysis of the insect cells, allowing the production of recombinant protein complexes at very high levels while the cells seemingly remained intact [11] . The MultiBac baculovirus/insect cell expression vector system for producing complex protein biologics abstract: The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. MultiBac has allowed the structure and function of many molecular machines to be elucidated, including previously inaccessible high-value drug targets. More recently, MultiBac developments have shifted to customized baculoviral genomes that are tailored for a range of applications, including synthesizing artificial proteins by genetic code expansion. We review some of these developments, including the ongoing rewiring of the MultiBac system for mammalian applications, notably CRISPR/Cas9-mediated gene editing. url: https://doi.org/10.1186/s12915-017-0447-6 doi: 10.1186/s12915-017-0447-6 id: cord-002967-yy3bennu author: Penna, Fabio title: Modulating Metabolism to Improve Cancer-Induced Muscle Wasting date: 2018-01-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Muscle wasting is one of the main features of cancer cachexia, a multifactorial syndrome frequently occurring in oncologic patients. The onset of cachexia is associated with reduced tolerance and response to antineoplastic treatments, eventually leading to clinical conditions that are not compatible with survival. Among the mechanisms underlying cachexia, protein and energy dysmetabolism play a major role. In this regard, several potential treatments have been proposed, mainly on the basis of promising results obtained in preclinical models. However, at present, no treatment yet reached validation to be used in the clinical practice, although several drugs are currently tested in clinical trials for their ability to improve muscle metabolism in cancer patients. Along this line, the results obtained in both experimental and clinical studies clearly show that cachexia can be effectively approached by a multidirectional strategy targeting nutrition, inflammation, catabolism, and inactivity at the same time. In the present study, approaches aimed to modulate muscle metabolism in cachexia will be reviewed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896402/ doi: 10.1155/2018/7153610 id: cord-014901-d9szap94 author: Permyakova, N. V. title: State of research in the field of the creation of plant vaccines for veterinary use date: 2015-01-04 words: 8091.0 sentences: 343.0 pages: flesch: 41.0 cache: ./cache/cord-014901-d9szap94.txt txt: ./txt/cord-014901-d9szap94.txt summary: Transgenic plants as an alternative of costly systems of recombinant immunogenic protein expression are the source for the production of cheap and highly efficient biotherapeuticals of new generation, including plant vaccines. Of principal importance of this work development was the creation of the "edible vaccine" concept, the essence of which is the use of genetically modified plants containing protein anti gens of infectious agents for oral delivery of relevant antigens to the mucosa of the gastrointestinal tract of warm blooded animals. Preparation of medicinal substances for the pro duction of veterinary products is based on various approaches, including biotechnology using genetically modified (transgenic) organisms for these purposes; such expression systems as bacteria, yeast, cells of insects and mammals are used. This review is devoted to the analysis of possibilities of producing recombinant immunogenic proteins for veterinary use on the basis of plant expression systems, and the history of the concept of "edible vaccines" for animal immunization. abstract: Transgenic plants as an alternative of costly systems of recombinant immunogenic protein expression are the source for the production of cheap and highly efficient biotherapeuticals of new generation, including plant vaccines. In the present review, possibilities of plant system application for the production of recombinant proteins for veterinary use are considered, the history of the “edible vaccine” concept is briefly summarized, advantages and disadvantages of various plant systems for the expression of recombinant immunogenic proteins are discussed. The list of recombinant plant vaccines for veterinary use, which are at different stages of clinical trials, is presented. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089518/ doi: 10.1134/s1021443715010100 id: cord-150183-zzzyewjb author: Phillips, J. C. title: Synchronized Attachment and the Darwinian Evolution of Coronaviruses CoV-1 and CoV-2 date: 2020-08-27 words: 2483.0 sentences: 154.0 pages: flesch: 55.0 cache: ./cache/cord-150183-zzzyewjb.txt txt: ./txt/cord-150183-zzzyewjb.txt summary: These are (CoV-1 site numbering from Uniprot P59594): 546Gln to Leu; 556 and 561Ser to Ala; and 568Ser to Leu. The differences associated with each of these mutations are hydropathically large (~50-100 in the MZ scale [4] ; all 20 amino acids span a range from most hydrophilic to most hydrophobic of 170). The central hydrophilic level set, absent from CoV-1 and present in CoV-2, is our main result ( There is an excellent review of the principles of self-organized criticality in living matter [3] . Some readers may be interested in the connections between hydropathic scaling theory of proteins and the more general synchronization of complex networks. Now that we are in the genomic age, with a very large sequence data base available for many proteins and many species, the discovery of these 20 fractals [5, 13] opens a new biophysics field of accurate thermodynamic analysis of small but medically important evolutionary differences. abstract: CoV2019 has evolved to be much more dangerous than CoV2003. Experiments suggest that structural rearrangements dramatically enhance CoV2019 activity. We identify a new first stage of infection which precedes structural rearrangements by using biomolecular evolutionary theory to identify sequence differences enhancing viral attachment rates. We find a small cluster of mutations which show that CoV-2 has a new feature that promotes much stronger viral attachment and enhances contagiousness. The extremely dangerous dynamics of human coronavirus infection is a dramatic example of evolutionary approach of self-organized networks to criticality. It may favor a very successful vaccine. The identified mutations can be used to test the present theory experimentally. url: https://arxiv.org/pdf/2008.12168v2.pdf doi: nan id: cord-193133-puqcbf8t author: Piplani, Sakshi title: In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus date: 2020-05-13 words: 3815.0 sentences: 215.0 pages: flesch: 51.0 cache: ./cache/cord-193133-puqcbf8t.txt txt: ./txt/cord-193133-puqcbf8t.txt summary: The devastating impact of the COVID19 pandemic caused by SARS coronavirus 2 (SARSCoV2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in susceptibilities across animal species. Here we show how computational chemistry methods from structure-based drug design can be used to determine the relative binding affinities of the SARS-CoV-2 spike protein for its receptor, angiotensin converting enzyme (ACE)-2, a critical initiating event for SARS-CoV-2 infection, across multiple common and exotic animal species. 31, 32 Molecular docking was performed on the homology modelled SARS-CoV-2 spike protein with human and animal ACE2 proteins. The molecular dynamics simulation of complexes of SARS-CoV-2 spike protein and ACE2 receptors of various species were performed for 100ns. abstract: The devastating impact of the COVID19 pandemic caused by SARS coronavirus 2 (SARSCoV2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in susceptibilities across animal species. Traditional lab-based methods will ultimately answer many of these questions but take considerable time. In silico modeling methods provide the opportunity to rapidly generate information on newly emerged pathogens to aid countermeasure development and also to predict potential future behaviors. We used a structural homology modeling approach to characterize the SARSCoV2 spike protein and predict its binding strength to the human ACE2 receptor. We then explored the possible transmission path by which SARSCoV2 might have crossed to humans by constructing models of ACE2 receptors of relevant species, and calculating the binding energy of SARSCoV2 spike protein to each. Notably, SARSCoV2 spike protein had the highest overall binding energy for human ACE2, greater than all the other tested species including bat, the postulated source of the virus. This indicates that SARSCoV2 is a highly adapted human pathogen. Of the species studied, the next highest binding affinity after human was pangolin, which is most likely explained by a process of convergent evolution. Binding of SARSCoV2 for dog and cat ACE2 was similar to affinity for bat ACE2, all being lower than for human ACE2, and is consistent with only occasional observations of infections of these domestic animals. Overall, the data indicates that SARSCoV2 is uniquely adapted to infect humans, raising questions as to whether it arose in nature by a rare chance event or whether its origins lie elsewhere. url: https://arxiv.org/pdf/2005.06199v1.pdf doi: nan id: cord-352481-iq3wor3w author: Postic, Guillaume title: An information gain-based approach for evaluating protein structure models date: 2020-08-18 words: 6518.0 sentences: 328.0 pages: flesch: 52.0 cache: ./cache/cord-352481-iq3wor3w.txt txt: ./txt/cord-352481-iq3wor3w.txt summary: Although these statistical potentials are not to be confused with their physics-based counterparts of the same name—i.e. PMFs obtained by molecular dynamics simulations—their particular success in assessing the native-like character of protein structure predictions has lead authors to consider the computed scores as approximations of the free energy. In this article, we present a conceptually new method for ranking protein structure models by quality, which is (i) independent of any physics-based explanation and (ii) relevant to statistics and to a general definition of information gain. As a proof of concept, we have built two scoring functions, respectively based on the new and the PMF equations, and compared their performance at ranking predicted structures of proteins by their quality. Using the reference dataset 3DRobot (n=60,200 structures) [35] , we show that the scoring function built with our new formalism is more accurate than statistical PMFs, based on three types of performance evaluation. abstract: For three decades now, knowledge-based scoring functions that operate through the “potential of mean force” (PMF) approach have continuously proven useful for studying protein structures. Although these statistical potentials are not to be confused with their physics-based counterparts of the same name—i.e. PMFs obtained by molecular dynamics simulations—their particular success in assessing the native-like character of protein structure predictions has lead authors to consider the computed scores as approximations of the free energy. However, this physical justification is a matter of controversy since the beginning. Alternative interpretations based on Bayes’ theorem have been proposed, but the misleading formalism that invokes the inverse Boltzmann law remains recurrent in the literature. In this article, we present a conceptually new method for ranking protein structure models by quality, which is (i) independent of any physics-based explanation and (ii) relevant to statistics and to a general definition of information gain. The theoretical development described in this study provides new insights into how statistical PMFs work, in comparison with our approach. To prove the concept, we have built interatomic distance-dependent scoring functions, based on the former and new equations, and compared their performance on an independent benchmark of 60,000 protein structures. The results demonstrate that our new formalism outperforms statistical PMFs in evaluating the quality of protein structural decoys. Therefore, this original type of score offers a possibility to improve the success of statistical PMFs in the various fields of structural biology where they are applied. The open-source code is available for download at https://gitlab.rpbs.univ-paris-diderot.fr/src/ig-score. url: https://doi.org/10.1016/j.csbj.2020.08.013 doi: 10.1016/j.csbj.2020.08.013 id: cord-029957-q7v5gli8 author: Prabhu, D. title: In silico Functional Annotation and Characterization of Hypothetical Proteins from Serratia marcescens FGI94 date: 2020-07-31 words: 5796.0 sentences: 311.0 pages: flesch: 42.0 cache: ./cache/cord-029957-q7v5gli8.txt txt: ./txt/cord-029957-q7v5gli8.txt summary: Two proteins AGB81206.1 and AGB83112.1 were predicted as a member of the exonuclease-endonuclease-phosphate domain super family which plays a crucial role in the intracellular signaling activities in bacteria (Dlakic, 2000) . The observed function of the HPs helps to understand the crucial role of new proteins in bacterial growth and can be targeted as a potential targets for drug discovery. The protein AGB80728.1 was predicted as Translocation and Assembly Module (TAM), which plays a major role in outer membrane biogenesis and virulence mechanisms in bacterial kingdom (Josts et al., 2017) . This kind of proteins are found in wide variety of prokaryotic and eukaryotic organisms and plays an vital role in cell processes and associated with virulence mechanisms of bacterial pathogens (Cerveny et al., 2013) . Various types of enzymes, transporters, cell division, binding proteins were characterized which play an essential role in the growth, survival virulence and pathogenesis of S. abstract: Serratia marcescens, rod-shaped Gram-negative bacteria is classified as an opportunistic pathogen in the family Enterobacteriaceae. It causes a wide variety of infections in humans, including urinary, respiratory, ocular lens and ear infections, osteomyelitis, endocarditis, meningitis and septicemia. Unfortunately, over the past decade, antibiotic resistance has become a serious health care issue; the effective means to control and dissemination of S. marcescens resistance is the need of hour. The whole genome sequencing of S. marcescens FGI94 strain contains 4434 functional proteins, among which 690 (15.56%) proteins were classified under hypothetical. In the present study, we applied the power of various bioinformatics tools on the basis of protein family comparison, motifs, functional properties of amino acids and genome context to assign the possible functions for the HPs. The pseudo sequences (protein sequence that contain ≤100 amino acid residues) are eliminated from the study. Although we have successfully predicted the function for 483 proteins, we were able to infer the high level of confidence only for 108 proteins. The predicted HPs were classified into various classes such as enzymes, transporters, binding proteins, cell division, cell regulatory and other proteins. The outcome of the study could be helpful to understand the molecular mechanism in bacterial pathogenesis and also provide an insight into the identification of potential targets for drug and vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394047/ doi: 10.1134/s1062359020300019 id: cord-294677-l1b4mw9d author: Prashantha, C.N. title: Molecular screening of antimalarial, antiviral, anti-inflammatory and HIV protease inhibitors against spike glycoprotein of Coronavirus date: 2020-10-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Target spike protein docking with antimalarial, antimicrobial, anti-inflammatory and HIV-Protease inhibitors. The docking processed using AutoDock Vina and the binding affinity score is noted based on kcal/mol and estimated inhibitory constant (KI). [Figure: see text] url: https://www.sciencedirect.com/science/article/pii/S1093326320305581?v=s5 doi: 10.1016/j.jmgm.2020.107769 id: cord-022235-6ircruag author: Pugsley, Anthony P. title: Later stages in the eukaryotic secretory pathway date: 2012-12-02 words: 15217.0 sentences: 667.0 pages: flesch: 52.0 cache: ./cache/cord-022235-6ircruag.txt txt: ./txt/cord-022235-6ircruag.txt summary: Microinjected antibodies recognizing the C-terminal, cytoplasmic tails of plasma membrane proteins can prevent their trans port to the cell surface (25, 590) , but this is probably due to antibodyinduced changes in protein conformation which make the protein incom petent for transport along the secretory pathway, rather than to inhibition of receptor-secretory protein interactions. (545) found that pro-a-factor processing was blocked by sec mutations, which prevented protein movement through the Golgi, and that mature α factor was normally present in secretory vesicles en route to the cell surface. The TGN is the most acidic Golgi compartment, although the pH is almost certainly not as low as in secretory granules (823) or in lysosomal sorting vesicles, in which low pH causes the dissociation of lysosomal proteins from the mannose-6-phosphate receptor (577) (see Section V.G.5). (1022) also observed the transient accumulation of one of these enzymes in coated vesicles, which, they proposed, are specifically involved in the sorting of lysosomal proteins from the secretory pathway. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155473/ doi: 10.1016/b978-0-12-566770-8.50009-4 id: cord-274424-juj71nc5 author: Pulford, David J. title: Intracellular processing of the porcine coronavirus transmissible gastroenteritis virus spike protein expressed by recombinant vaccinia virus date: 1991-06-30 words: 4901.0 sentences: 231.0 pages: flesch: 49.0 cache: ./cache/cord-274424-juj71nc5.txt txt: ./txt/cord-274424-juj71nc5.txt summary: Abstract The Spike (S) protein from a virulent British field isolate of porcine transmissible gastroenteritis virus (TGEV) FS772/70 was constructed from cDNA and inserted into the vaccinia virus (VV) thymidine kinase gene locus under the control of the VV early/late gene P7.5K promoter. In this paper we report the construction of a FS772/ 70 cDNA S gene and its expression by a recombinant vaccina virus (rVV) to study the antigenicity and cellular localization of the S protein. Expression of the recombinant spike antigens TGEV gene products synthesized by vTS-1 and vTSA-1 were analyzed by pulse labeling rVV-infected HTK-cells with L-[35S]methionine in the presence or absence of 10 pg ml-'' tunicamycin for 6 hr. The lack of detectable ~160 or ~130 in the culture medium of vTS-l-and vTSA-l-infected cells, respectively (Fig. 4 lanes 4 and 7) , could result from the levels being too low to be detected by the antibodies due to reduction in synthesis or the lack of glycosylation of the S protein in the presence of tunicamycin. abstract: Abstract The Spike (S) protein from a virulent British field isolate of porcine transmissible gastroenteritis virus (TGEV) FS772/70 was constructed from cDNA and inserted into the vaccinia virus (VV) thymidine kinase gene locus under the control of the VV early/late gene P7.5K promoter. Recombinant S protein was synthesized as an endo-β-N-acetylglucosamini-dase H (Endo H)-sensitive glycoprotein with high mannose simple oligosaccharides (gp190) that underwent post-translational modification to an Endo H-resistant glycoprotein with complex oligosaccharides (gp210). Immunofluorescence analysis demonstrated that the majority of recombinant S protein was retained at the Golgi but some S protein was expressed on the plasma membrane. Monoclonal antibodies (mAbs) raised against native S protein reacted with this recombinant S protein; also, mice infected with the recombinant vaccinia virus (rVV) expressing the S protein induced TGEV neutralizing antibodies. A truncated S protein (SΔ) was also expressed in rVV-infected cells by introducing a deletion into the S protein cDNA that removed 292 amino acids from the C-terminus. The SΔ protein (gpl70) was shown to be antigenically similar to TGEV S protein by immunofluorescence and immunoprecipitation tests but was retained in the endoplasmic reticulum and not expressed on the cell surface. url: https://api.elsevier.com/content/article/pii/004268229190617K doi: 10.1016/0042-6822(91)90617-k id: cord-004181-exbs3tz7 author: Pumchan, Ansaya title: Novel Chimeric Multiepitope Vaccine for Streptococcosis Disease in Nile Tilapia (Oreochromis niloticus Linn.) date: 2020-01-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Streptococcus agalactiae is a causative agent of streptococcosis disease in various fish species, including Nile tilapia (Oreochromis niloticus Linn.). Vaccination is an effective disease prevention and control method, but limitations remain for protecting against catastrophic mortality of fish infected with different strains of streptococci. Immunoproteomics analysis of S. agalactiae was used to identify antigenic proteins and construct a chimeric multiepitope vaccine. Epitopes from five antigenic proteins were shuffled in five helices of a flavodoxin backbone, and in silico analysis predicted a suitable RNA and protein structure for protein expression. 45F2 and 42E2 were identified as the best candidates for a chimeric multiepitope vaccine. Recombinant plasmids were constructed to produce a recombinant protein vaccine and DNA vaccine system. Overexpressed proteins were determined to be 30 kDa and 25 kDa in the E. coli and TK1 systems, respectively. The efficacy of the chimeric multiepitope construct as a recombinant protein vaccine and DNA vaccine was evaluated in Nile tilapia, followed by S. agalactiae challenge at 1 × 10(7) CFU/mL. Relative percentage survival (RPS) and cumulative mortality were recorded at approximately 57–76% and 17–30%, respectively. These chimeric multiepitope vaccines should be applied in streptococcosis disease control and developed into a multivalent vaccine to control multiple diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969146/ doi: 10.1038/s41598-019-57283-0 id: cord-341564-fvuwick5 author: Qi, Zhao-Hui title: Novel Method of 3-Dimensional Graphical Representation for Proteins and Its Application date: 2018-06-12 words: 2647.0 sentences: 178.0 pages: flesch: 54.0 cache: ./cache/cord-341564-fvuwick5.txt txt: ./txt/cord-341564-fvuwick5.txt summary: From these, we can see that physicochemical properties are widely applied with graphical representation of protein sequences by these researchers and their results seem well. In this article, we propose a 3-dimensional (3D) graphic representation of protein sequences based on 10 physicochemical properties [17] [18] [19] [20] [21] of amino acids and the BLOSUM62 matrix. In this article, we propose a 3-dimensional (3D) graphic representation of protein sequences based on 10 physicochemical properties [17] [18] [19] [20] [21] of amino acids and the BLOSUM62 matrix. Therefore, to mine essential information from a protein sequence, we propose an effective graphical method combining physicochemical properties of amino acids and the BLOSUM62 matrix. An efficient numerical method for protein sequences similarity analysis based on a new two-dimensional graphical representation F-Curve, a graphical representation of protein sequences for similarity analysis based on physicochemical properties of amino acids abstract: In this article, we propose a 3-dimensional graphical representation of protein sequences based on 10 physicochemical properties of 20 amino acids and the BLOSUM62 matrix. It contains evolutionary information and provides intuitive visualization. To further analyze the similarity of proteins, we extract a specific vector from the graphical representation curve. The vector is used to calculate the similarity distance between 2 protein sequences. To prove the effectiveness of our approach, we apply it to 3 real data sets. The results are consistent with the known evolution fact and show that our method is effective in phylogenetic analysis. url: https://www.ncbi.nlm.nih.gov/pubmed/29977111/ doi: 10.1177/1176934318777755 id: cord-310909-nc82a70n author: Qiu, Maofeng title: Antibody responses to individual proteins of SARS coronavirus and their neutralization activities date: 2005-04-13 words: 4520.0 sentences: 196.0 pages: flesch: 48.0 cache: ./cache/cord-310909-nc82a70n.txt txt: ./txt/cord-310909-nc82a70n.txt summary: In this study, 13 recombinant proteins associated with four structural proteins (S, E, M and N) and five putative uncharacterized proteins (3a, 3b, 6, 7a and 9b) of the SARS-CoV were prepared and used for screening and monitoring their specific IgG antibodies in SARS patient sera by protein microarray. In the present study, to understand the profile of antibodies to individual proteins of the SARS-CoV, 13 recombinant proteins associated with four structural proteins (S, E, M and N) and five putative uncharacterized proteins (3a, 3b, 6, 7a and 9b) of this virus were prepared and used to screen and monitor their specific IgG antibodies in SARS patient sera using protein microarray, and the rabbit antisera to recombi-nant proteins S3 (aa 241-591), N (full length), 3a (aa 125-274) and 9b (full length) were prepared and used to investigate their neutralizing activity to the SARS-CoV infection in Vero E6 cells. abstract: A novel coronavirus, the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), was identified as the causative agent of SARS. The profile of specific antibodies to individual proteins of the virus is critical to the development of vaccine and diagnostic tools. In this study, 13 recombinant proteins associated with four structural proteins (S, E, M and N) and five putative uncharacterized proteins (3a, 3b, 6, 7a and 9b) of the SARS-CoV were prepared and used for screening and monitoring their specific IgG antibodies in SARS patient sera by protein microarray. Antibodies to proteins S, 3a, N and 9b were detected in the sera from convalescent-phase SARS patients, whereas those to proteins E, M, 3b, 6 and 7a were undetected. In the detectable specific antibodies, anti-S and anti-N were dominant and could persist in the sera of SARS patients until week 30. Among the rabbit antisera to recombinant proteins S3, N, 3a and 9b, only anti-S3 serum showed significant neutralizing activity to the SARS-CoV infection in Vero E6 cells. The results suggest (1) that anti-S and anti-N antibodies are diagnostic markers and in particular that S3 is immunogenic and therefore is a good candidate as a subunit vaccine antigen; and (2) that, from a virus structure viewpoint, the presence in some human sera of antibodies reacting with two recombinant polypeptides, 3a and 9b, supports the hypothesis that they are synthesized during the virus cycle. url: https://www.ncbi.nlm.nih.gov/pubmed/15878679/ doi: 10.1016/j.micinf.2005.02.006 id: cord-003144-nqkw5v3w author: Qu, Zehui title: Label‐Free Quantitative Proteomic Analysis of Differentially Expressed Membrane Proteins of Pulmonary Alveolar Macrophages Infected with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Its Attenuated Strain date: 2017-11-24 words: 5514.0 sentences: 319.0 pages: flesch: 51.0 cache: ./cache/cord-003144-nqkw5v3w.txt txt: ./txt/cord-003144-nqkw5v3w.txt summary: title: Label‐Free Quantitative Proteomic Analysis of Differentially Expressed Membrane Proteins of Pulmonary Alveolar Macrophages Infected with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Its Attenuated Strain Significant differences exist between the highly pathogenic (HP) porcine reproductive and respiratory syndrome virus (PRRSV) and its attenuated pathogenic (AP) strain in the ability to infect host cells. This is the first attempt to explore the differential characteristics between HP‐PRRSV and its attenuated PRRSV infected PAMs focusing on membrane proteins which will be of great help to further understand the different infective mechanisms of HP‐PRRSV and AP‐PRRSV. Differentially expressed proteins between control and HP-PRRSV-infected cells (Con/HP) and the www.advancedsciencenews.com www.proteomics-journal.com p <0.01 and ratio >2 or <0.5 indicated quantitative difference between two groups. By analyzing detected proteins in HP-infected, AP-PRRSV-infected, and control group, proteins related to the immune response or virus replication were identified that may elucidate unique pathways used by different virulent PRRSVs for cell entry, virus replication, and immune escape mechanisms. abstract: Significant differences exist between the highly pathogenic (HP) porcine reproductive and respiratory syndrome virus (PRRSV) and its attenuated pathogenic (AP) strain in the ability to infect host cells. The mechanisms by which different virulent strains invade host cells remain relatively unknown. In this study, pulmonary alveolar macrophages (PAMs) are infected with HP‐PRRSV (HuN4) and AP‐PRRSV (HuN4‐F112) for 24 h, then harvested and subjected to label‐free quantitative MS. A total of 2849 proteins are identified, including 95 that are differentially expressed. Among them, 26 proteins are located on the membrane. The most differentially expressed proteins are involved in response to stimulus, metabolic process, and immune system process, which mainly have the function of binding and catalytic activity. Cluster of differentiation CD163, vimentin (VIM), and nmII as well as detected proteins are assessed together by string analysis, which elucidated a potentially different infection mechanism. According to the function annotations, PRRSV with different virulence may mainly differ in immunology, inflammation, immune evasion as well as cell apoptosis. This is the first attempt to explore the differential characteristics between HP‐PRRSV and its attenuated PRRSV infected PAMs focusing on membrane proteins which will be of great help to further understand the different infective mechanisms of HP‐PRRSV and AP‐PRRSV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084361/ doi: 10.1002/pmic.201700101 id: cord-338980-pygykil7 author: Rahaman, Jordon title: Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses date: 2016-11-09 words: 5801.0 sentences: 308.0 pages: flesch: 52.0 cache: ./cache/cord-338980-pygykil7.txt txt: ./txt/cord-338980-pygykil7.txt summary: Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. For the DISOPRED2 predictions that were inferred using the nr database, the continuous disorder propensities for every site in a protein were mapped onto their corresponding position in the multiple sequence alignment as raw disorder propensities and as binary states, order or disorder, using a cutoff of 5. For regions with five or more consecutive sites that were 100% conserved in sequence across 1) all CoV or 2) across the MERS and SARS clades, the information of structural disorder prediction from IUPred and DISOPRED2 was used to identify all ungapped sites that were consistently predicted to have 100% conserved order. abstract: Within the last 15 years, two related coronaviruses (Severe Acute Respiratory Syndrome [SARS]-CoV and Middle East Respiratory Syndrome [MERS]-CoV) expanded their host range to include humans, with increased virulence in their new host. Coronaviruses were recently found to have little intrinsic disorder compared with many other virus families. Because intrinsically disordered regions have been proposed to be important for rewiring interactions between virus and host, we investigated the conservation of intrinsic disorder and secondary structure in coronaviruses in an evolutionary context. We found that regions of intrinsic disorder are rarely conserved among different coronavirus protein families, with the primary exception of the nucleocapsid. Also, secondary structure predictions are only conserved across 50–80% of sites for most protein families, with the implication that 20–50% of sites do not have conserved secondary structure prediction. Furthermore, nonconserved structure sites are significantly less constrained in sequence divergence than either sites conserved in the secondary structure or sites conserved in loop. Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. The identified sequence motif is found within the nonstructural protein (NSP) 12 and constitutes an antiviral target potentially effective against the present day and future coronaviruses. On shorter evolutionary timescales, the SARS and MERS clades have more sequence motifs fulfilling the criteria applied. Interestingly, many motifs map to NSP12 making this a prime target for coronavirus antivirals. url: https://doi.org/10.1093/gbe/evw246 doi: 10.1093/gbe/evw246 id: cord-190540-zf5ksac2 author: Rakshit, Kausik title: An effective approach to reduce the penetration potential of Sars-Cov-2 and other viruses by spike protein: Through surface particle electrostatic charge negotiation date: 2020-06-18 words: 2065.0 sentences: 104.0 pages: flesch: 46.0 cache: ./cache/cord-190540-zf5ksac2.txt txt: ./txt/cord-190540-zf5ksac2.txt summary: title: An effective approach to reduce the penetration potential of Sars-Cov-2 and other viruses by spike protein: Through surface particle electrostatic charge negotiation Reviewing the works of different authors, regarding charges, surface charge densities ({sigma}), charge mobility ({mu}) and electrostatic potentials of different aerosols under varied experimental conditions, a similar intensive study has also been carried out to investigate the electron donating and accepting (hole donating) properties of the spike proteins (S-proteins) of different RNA and DNA viruses, including SARS-COV-2. The electrostatic charges accumulated in the layers between the Gr IV Ge is sufficient enough to either fuse or repel the charges of the spike proteins of the RNA, DNA viruses including SARS-Cov-2 (RNA virus) or the aerosols. abstract: The objective of this paper is to provide a mathematical model to construct a barrier that may be useful to prevent the penetration of different viruses (Eg. SARS-COV-2) as well as charged aerosols through the concept of electrostatic charge negotiation. (Fusion for the opposite types of charges and repulsion for the similar types of charges). Reviewing the works of different authors, regarding charges, surface charge densities ({sigma}), charge mobility ({mu}) and electrostatic potentials of different aerosols under varied experimental conditions, a similar intensive study has also been carried out to investigate the electron donating and accepting (hole donating) properties of the spike proteins (S-proteins) of different RNA and DNA viruses, including SARS-COV-2. Based upon the above transport properties of electrons of different particles having different dimensions, a mathematical model has been established to find out the penetration potential of those particles under different electrostatic fields. An intensive study have been carried out to find out the generation of electrostatic charges due to the surface emission of electrons (SEE), when a conducting material like silk, nylon or wool makes a friction with the Gr IV elements like Germanium or Silicon, it creates an opposite layer of charges in the outer conducting surface and the inner semiconducting surface separated by a dielectric materials. This opposite charge barriers may be considered as Inversion layers (IL). The electrostatic charges accumulated in the layers between the Gr IV Ge is sufficient enough to either fuse or repel the charges of the spike proteins of the RNA, DNA viruses including SARS-Cov-2 (RNA virus) or the aerosols. url: https://arxiv.org/pdf/2006.10603v1.pdf doi: nan id: cord-339558-li65qvq9 author: Rana, Rashmi title: A comprehensive overview of proteomics approach for COVID 19: new perspectives in target therapy strategies date: 2020-11-02 words: 5934.0 sentences: 334.0 pages: flesch: 44.0 cache: ./cache/cord-339558-li65qvq9.txt txt: ./txt/cord-339558-li65qvq9.txt summary: Structural proteome analysis of earlier SARS epidemic in 2003 revealed a large array of proteins that could be targeted for this pandemic too. They used affinity purification followed by mass spectrometry analysis and statistical modeling of the MS1level quantitative data which allowed the identification of 1484 interactions between 1086 cellular proteins and 24 SARS-CoV bait proteins. 2013 ) A recently published study involves the development of an Opto-microfluidic sensing platform to rapidly detect antibodies against SARS-CoV2 spike protein in diluted human plasma with high sensitivity. It is the first study to detect the SARS-CoV-2 antigens in the blood plasma of COVID-19-positive patients. Mass spectrometric identification of SARS-CoV-2 proteins from gargle solution samples of COVID-19 patients Development of mass spectrometry-based targeted assay for direct detection of novel SARS-CoV-2 coronavirus from clinical specimens A rapid and sensitive method to detect SARS-CoV-2 virus using targeted-mass spectrometry abstract: World Health Organisation declared COVID-19 a pandemic on March 11, 2020. It was temporarily named as 2019-nCoV then subsequently named as COVID-19 virus. A coronavirus is a group of viruses, known to be zoonotic, causing illness ranging from acute to mild respiratory infections. These are spherical or pleomorphic enveloped particles containing positive sense RNA. The virus enters host cells, its uncoated genetic material transcribes, and translates. Since it has started spreading rapidly, protective measures have been taken all over the world. However, its transmission has been proved to be unstoppable and the absence of an effective drug makes the situation worse. The scientific community has gone all-out to discover and develop a possible vaccine or a competent antiviral drug. Other domains of biological sciences that promise effective results and target somewhat stable entities that are proteins, could be very useful in this time of crisis. Proteomics and metabolomics are the vast fields that are equipped with sufficient technologies to face this challenge. Various protein separation and identification techniques are available which facilitates the analysis of various types of interactions among proteins and their evolutionary lineages. The presented review aims at confronting the question: ‘how proteomics can help in tackling SARS-CoV-2?’ It deals with the role of upcoming proteome technology in these pandemic situations and discusses the proteomics approach towards the COVID-19 dilemma. url: https://www.ncbi.nlm.nih.gov/pubmed/33162722/ doi: 10.1007/s42485-020-00052-9 id: cord-018493-q24f86e9 author: Ranjan, Prabhat title: Importance of Natural Proteins in Infectious Diseases date: 2015-08-08 words: 3930.0 sentences: 209.0 pages: flesch: 39.0 cache: ./cache/cord-018493-q24f86e9.txt txt: ./txt/cord-018493-q24f86e9.txt summary: Other extracellular proteins like invasive enzymes, e.g., coagulase, contributes to the formation of fibrin walls around staphylococcal lesions [10] ; exotoxins (proteins released extracellularly), like neurotoxin (Tetanus toxin, by Clostridium tetani, Botulinum toxin by Clostridium botulinum) [11] and cytotoxins (Diphtheria toxin produced by Corynebacterium dipthereae) [12, 13] , also known as A-B toxins (consisting of 2 subunits: one binds to cell surface receptor and the other is transferred into the cell to damage the cell) [14] , cytolytic toxins (attacking cell constituents causing lysis) like hemolysins produced by Bordetella pertussis, inducing apoptosis of host cells, super antigen toxins (e.g., superantigen, sized 22KDa produced by 5-25 % of Staphylococcus aureus isolates, causing toxic shock syndrome (TSS) by stimulating the release of large amounts of interleukin-1, interleukin-2 and tumor necrosis factor, etc.) [15] . Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are a group of evolutionarily conserved intracellular proteinaceous PRRs that play a vital role in innate immunity and host physiology, in both plants and animals [30, 31] . Heat shock proteins can be expressed on the surface of infected cells, and this is likely to provide a target for the innate immune response. abstract: Proteins are important biomolecules, extensively involved in almost all biological processes. A number of proteins are also implicated in infectious diseases. Bacterial proteins used in adhesion to host epithelium, bacterial toxins, and viral membrane glycoproteins are some of the proteins involved in infectious diseases. Even components of the host innate immune system like Toll-like receptors and Nod-like receptors and adaptive immune components like immunoglobulins aiding in defense against pathogens are important biological proteins. Chaperones like acid and heat shock proteins provide protection from high temperatures, metabolic poisons, and other stressful conditions. Several natural and artificial proteins are components of vaccines, a key strategy to control fatal diseases, lacking empirical treatment. It is necessary to investigate these proteins, to develop new biomedical tools and technologies, aiding in eradication of various diseases. Thus, further research should be carried out in this field, for saving and improving quality of human lives. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123379/ doi: 10.1007/978-81-322-2491-4_8 id: cord-011012-5mev3otu author: Rathore, Abhishek Singh title: Production and immunogenicity of Fubc subunit protein redesigned from DENV envelope protein date: 2020-03-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dengue virus (DENV) is a vector-borne human pathogen that usually causes dengue fever; however, sometime it leads to deadly complications such as dengue with warning signs (DWS+) and severe dengue (SD). Several studies have shown that fusion (Fu) and bc loop of DENV envelope domain II are highly conserved and consist some of the most dominant antigenic epitopes. Therefore, in this study, Fu and bc loops were joined together to develop a short recombinant protein as an alternative of whole DENV envelope protein, and its immunogenic potential as fusion peptide was estimated. For de novo designing of the antigen, Fu and bc peptides were linked with an optimised linker so that the three dimensional conformation was maintained as it is in DENV envelope protein. The redesigned Fubc protein was expressed in E. coli and purified. Subsequently, structural integrity of the purified protein was verified by CD spectroscopy. To characterise immune responses against recombinant Fubc protein, BALB/c mice were subcutaneously injected with emulsified antigen preparation. It was observed by ELISA that Fubc fusion protein elicited higher serum IgG antibody response either in the presence or in absence of Freund’s adjuvant in comparison to the immune response of Fu and bc peptides separately. Furthermore, the binding of Fubc protein with mice antisera was validated by SPR analysis. These results suggest that Fu and bc epitope-based recombinant fusion protein could be a potential candidate towards the development of the effective subunit vaccine against DENV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-020-10541-y) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223326/ doi: 10.1007/s00253-020-10541-y id: cord-298802-a5h91axf author: Ravindran, Madhu Sudhan title: Molecular chaperones: from proteostasis to pathogenesis date: 2018-06-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Maintaining protein homeostasis (proteostasis) is essential for a functional proteome. A wide range of extrinsic and intrinsic factors perturb proteostasis, causing protein misfolding, misassembly, and aggregation. This compromises cellular integrity and leads to aging and disease, including neurodegeneration and cancer. At the cellular level, protein aggregation is counteracted by powerful mechanisms comprising of a cascade of enzymes and chaperones that operate in a coordinated multistep manner to sense, prevent, and/or dispose of aberrant proteins. Although these processes are well understood for soluble proteins, there is a major gap in our understanding of how cells handle misfolded or aggregated membrane proteins. This article provides an overview of cellular proteostasis with emphasis on membrane protein substrates and suggests host–virus interaction as a tool to clarify outstanding questions in proteostasis. url: https://doi.org/10.1111/febs.14576 doi: 10.1111/febs.14576 id: cord-199630-2lmwnfda author: Ray, Sumanta title: Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs date: 2020-07-05 words: 6389.0 sentences: 379.0 pages: flesch: 53.0 cache: ./cache/cord-199630-2lmwnfda.txt txt: ./txt/cord-199630-2lmwnfda.txt summary: Therefore, host-(1) We link existing high-quality, long-term curated and refined, large scale drug/protein -protein interaction data with (2) molecular interaction data on SARS-CoV-2 itself, raised only a handful of weeks ago, (3) exploit the resulting overarching network using most advanced, AI boosted techniques (4) for repurposing drugs in the fight against SARS-CoV-2 (5) in the frame of HDT based strategies. As for (3)-(5), we will highlight interactions between SARS-Cov-2-host protein and human proteins important for the virus to persist using most advanced deep learning techniques that cater to exploiting network data. As per our simulation study, a large fraction, if not the vast majority of the predictions establish true, hence actionable interactions between drugs on the one hand and SARS-CoV-2 associated human proteins (hence of use in HDT) on the other hand. abstract: Coronavirus Disease 2019 (COVID-19) has been creating a worldwide pandemic situation. Repurposing drugs, already shown to be free of harmful side effects, for the treatment of COVID-19 patients is an important option in launching novel therapeutic strategies. Therefore, reliable molecule interaction data are a crucial basis, where drug-/protein-protein interaction networks establish invaluable, year-long carefully curated data resources. However, these resources have not yet been systematically exploited using high-performance artificial intelligence approaches. Here, we combine three networks, two of which are year-long curated, and one of which, on SARS-CoV-2-human host-virus protein interactions, was published only most recently (30th of April 2020), raising a novel network that puts drugs, human and virus proteins into mutual context. We apply Variational Graph AutoEncoders (VGAEs), representing most advanced deep learning based methodology for the analysis of data that are subject to network constraints. Reliable simulations confirm that we operate at utmost accuracy in terms of predicting missing links. We then predict hitherto unknown links between drugs and human proteins against which virus proteins preferably bind. The corresponding therapeutic agents present splendid starting points for exploring novel host-directed therapy (HDT) options. url: https://arxiv.org/pdf/2007.02338v1.pdf doi: nan id: cord-000674-36jzzy77 author: Reggiori, Fulvio title: Autophagy: More Than a Nonselective Pathway date: 2012-05-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Autophagy is a catabolic pathway conserved among eukaryotes that allows cells to rapidly eliminate large unwanted structures such as aberrant protein aggregates, superfluous or damaged organelles, and invading pathogens. The hallmark of this transport pathway is the sequestration of the cargoes that have to be degraded in the lysosomes by double-membrane vesicles called autophagosomes. The key actors mediating the biogenesis of these carriers are the autophagy-related genes (ATGs). For a long time, it was assumed that autophagy is a bulk process. Recent studies, however, have highlighted the capacity of this pathway to exclusively eliminate specific structures and thus better fulfil the catabolic necessities of the cell. We are just starting to unveil the regulation and mechanism of these selective types of autophagy, but what it is already clearly emerging is that structures targeted to destruction are accurately enwrapped by autophagosomes through the action of specific receptors and adaptors. In this paper, we will briefly discuss the impact that the selective types of autophagy have had on our understanding of autophagy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362037/ doi: 10.1155/2012/219625 id: cord-261159-9pkg7mbh author: Regnier, Fred E. title: Chromatography of complex protein mixtures date: 1987-07-17 words: 10934.0 sentences: 565.0 pages: flesch: 51.0 cache: ./cache/cord-261159-9pkg7mbh.txt txt: ./txt/cord-261159-9pkg7mbh.txt summary: Although large amounts of organic solvent are occasionally used in the mobile phase to solubilize proteins, as in the case of chloroplast proteins [ 181, most IEC separations are carried out with either non-ionic detergents or the 3-[ ( 3-chloroamidopropyl) dimethylammonio] -l-trifluoroacetic acid ( CHAPS) zwitterion [ 24,251. Using a series of polyethylene glycol alkyl ether (C,E,) detergents as a mobile phase additive it was possible to show that both alkyl chain length and the number of glycol residues influenced resolution of Escherichiu coZi K-12 membrane proteins in anion-exchange separations [ 191 (C&E, was optimal) . Elution of proteins and peptide fragments from RPC columns was achieved with mobile phases containing 5% formic acid. In the case of red blood cell membrane proteins, the resolution of 1000 A pore diameter organic resin-based sorbents was superior to 300 A pore diameter silica-based materials when the columns were eluted with a TFA-acetonitrile mobile phase [ 261. abstract: Abstract This review has shown that a variety of chromatographic techniques are available for fractionating proteins. Fortunately, high-quality columns of every type described in this review are commercially available. Most water-soluble proteins may be eluted from size-exclusion, hydrophobic-interaction, ion-exchange, metal chelate, and bioaffinity columns with ease. When this is the case, high recovery and retention of biological activity are the norm. The exception is reversed-phase chromatography where the organic solvents and acids used in polypeptide elution denature many proteins. When problems do occur, they are generally the result of unique structural features of the protein. Very hydrophobic proteins have presented the biggest problem in that they are difficult to solubilize, particularly with retention of biological activity. It has been found that zwitterionic an non-ionic detergents are the most suitable solubilizing agents, but area has also been used in cases where hydrophobic interacts are not as strong. Unfortunately, there is still an element of trial-and-error in selecting the most suitable solubilizing agent. Heterogeneous glycosylation of proteins also presents a problem. Both neutral and charged monosaccharides can be incorporated into proteins through multiple steps at several sites. Thus, there is the potential in a sample for a large number of glycoprotein species which have the same polypeptide backbone and differing amounts of oligosaccharide. A problem arises when size-exclusion, ion-exchange, hydrophobic-interaction, reversed-phase and bioaffinity systems begin to discriminate between these very similar glycoprotein species. Chromatographic peaks can become very load, due to incomplete fractionation, and the polypeptide chain of interest can be associated with multiple peaks. The separation of glycoproteins requires much more study before logical procedures can be suggested for column selection and operation. Aggregated species are another class of proteins which present occasional problems. Multimeric proteins are adsorbed to sorbents by a series of forces, among which are hydrogen bonding, hydrophobic interactions, and electrostatic forces. These forces are also responsible for the maintenance of quaternary structure in proteins. When the same forces dominate both retention of protein structure and adsorption at the sorbent surface, the quaternary structure of the protein can be disrupted during elution. Very basic proteins also present a problem in some cases. Columns with residual negative charges, such as a silica-based reversed-phase column, adsorb anionic species so strongly that they are difficult to elute. This is the case with ribosomal and nucleoproteins. The solution is to use exhaustively end-capped columns which diminish electrostatic interactions. url: https://www.sciencedirect.com/science/article/pii/0378434787800075 doi: 10.1016/0378-4347(87)80007-5 id: cord-018479-mvnm98hv author: Rehm, Fabian B. H. title: Applications of Microbial Biopolymers in Display Technology date: 2017-11-16 words: 4621.0 sentences: 227.0 pages: flesch: 35.0 cache: ./cache/cord-018479-mvnm98hv.txt txt: ./txt/cord-018479-mvnm98hv.txt summary: Such beads have been demonstrated in diverse applications, including fluorescence-activated cell sorting, enzyme-linked immunosorbent assays, microarrays, diagnostic skin test for tuberculosis, vaccines, protein purification, and affinity bioseparation. Most recently, PHA inclusions with GFP and MOG fused to PhaP or PhaC, such that each granule is simultaneously displaying two protein-based functionalities, were examined in the context of FACS, providing proof-of-concept for the biotechnological application of bifunctional PHA beads which may extend beyond FACS ). This study demonstrated that V HH domains from camelid antibodies, designed ankyrin repeat proteins (DARPins) and OB-folds (OBodies), could be densely displayed on PHA beads resulting in high affinity binding resins for purification of various target proteins. Overall, PhaC engineering such as N-or C-terminal fusions and/or insertions enabled efficient display of binding domains for interaction with target compounds resulting in purification performance suitable for application as bioseparation resin. abstract: Microorganisms produce a variety of different polymers such as polyamides, polysaccharides, and polyesters. The polyesters, the polyhydroxyalkanoates (PHAs), are the most extensively studied polymers in regard to their use in display technology. The material properties of bacterial PHAs in combination with their biocompatibility and biodegradability make them attractive substrates for use in display technology applications. By translationally fusing bioactive molecules to a gene encoding a PHA-binding domain, the appropriate functionalization for a given application can be achieved such that the need for chemical immobilization is circumvented. By separately extracting and processing the biopolymer, using it to coat a surface, and then treating this surface with the fusion proteins, surface functionalization for immunodiagnostic microarray or tissue engineering applications can be accomplished. Conversely, by expressing the fusion protein directly in the PHA-producing organisms, one-step production of functionalized beads can be achieved. Such beads have been demonstrated in diverse applications, including fluorescence-activated cell sorting, enzyme-linked immunosorbent assays, microarrays, diagnostic skin test for tuberculosis, vaccines, protein purification, and affinity bioseparation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123360/ doi: 10.1007/978-3-319-50436-0_377 id: cord-010604-3d37o05y author: Rein, Theo title: Post-translational modifications and stress adaptation: the paradigm of FKBP51 date: 2020-04-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Adaptation to stress is a fundamental requirement to cope with changing environmental conditions that pose a threat to the homeostasis of cells and organisms. Post-translational modifications (PTMs) of proteins represent a possibility to quickly produce proteins with new features demanding relatively little cellular resources. FK506 binding protein (FKBP) 51 is a pivotal stress protein that is involved in the regulation of several executers of PTMs. This mini-review discusses the role of FKBP51 in the function of proteins responsible for setting the phosphorylation, ubiquitination and lipidation of other proteins. Examples include the kinases Akt1, CDK5 and GSK3β, the phosphatases calcineurin, PP2A and PHLPP, and the ubiquitin E3-ligase SKP2. The impact of FKBP51 on PTMs of signal transduction proteins significantly extends the functional versatility of this protein. As a stress-induced protein, FKBP51 uses re-setting of PTMs to relay the effect of stress on various signaling pathways. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200631/ doi: 10.1042/bst20190332 id: cord-321275-7haq0e38 author: Renzi, Fabiana title: Large-scale purification and crystallization of the endoribonuclease XendoU: troubleshooting with His-tagged proteins date: 2006-02-28 words: 1971.0 sentences: 101.0 pages: flesch: 58.0 cache: ./cache/cord-321275-7haq0e38.txt txt: ./txt/cord-321275-7haq0e38.txt summary: The tendency of the recombinant enzyme to aggregate could be reversed upon the addition of chelating agents (EDTA, imidazole): aggregation is a potential drawback when purifying and crystallizing His-tagged proteins, which are widely used, especially in high-throughput structural studies. Subsequent screening resulted in the growth of crystals (300 Â 300 Â 300 mm) in 40% (NH 4 ) 2 SO 4 , 0.2 M sodium citrate pH 6 at 293 K which belonged to space group P3 1 21 but diffracted poorly; the resolution was improved by cocrystallization with 50 mM uridine 5 0 -monophosphate (5 0 -UMP), which may bind to the active site, possibly inducing the stabilization of flexible regions (Fig. 2a) . Large-scale expression of His-tagged XendoU resulted in soluble protein that was heterogeneously aggregated, a condition that affects crystallization (Wilson, 2003) . abstract: XendoU is the first endoribonuclease described in higher eukaryotes as being involved in the endonucleolytic processing of intron-encoded small nucleolar RNAs. It is conserved among eukaryotes and its viral homologue is essential in SARS replication and transcription. The large-scale purification and crystallization of recombinant XendoU are reported. The tendency of the recombinant enzyme to aggregate could be reversed upon the addition of chelating agents (EDTA, imidazole): aggregation is a potential drawback when purifying and crystallizing His-tagged proteins, which are widely used, especially in high-throughput structural studies. Purified monodisperse XendoU crystallized in two different space groups: trigonal P3(1)21, diffracting to low resolution, and monoclinic C2, diffracting to higher resolution. url: https://www.ncbi.nlm.nih.gov/pubmed/16511328/ doi: 10.1107/s1744309106006373 id: cord-320713-b37c8aye author: Roberts, Lisa O. title: Chapter 9 Viral Strategies to Subvert the Mammalian Translation Machinery date: 2009-10-27 words: 20205.0 sentences: 1067.0 pages: flesch: 48.0 cache: ./cache/cord-320713-b37c8aye.txt txt: ./txt/cord-320713-b37c8aye.txt summary: 6 The rate of translation initiation in mammalian cells is also controlled by sequence elements within the 5 0 -and 3 0 -UTRs of mRNAs which regulate this process by providing sites for interaction of regulatory proteins and RNAs. These include upstream open reading frames (uORFs), microRNA (miRNA) target sites, and polyadenylation elements. 5 It was suggested that alternative eIF4F complexes lacking PABP could selectively promote the synthesis of viral, but not host, proteins, so that KSHV-encoded mRNAs would compete more effectively for host translation machinery in infected cells. Picornavirus translation is directed by internal ribosome entry sites (IRESs) within the 5 0 -UTRs of the viral RNAs. The central one-third of eIF4G, containing the eIF3 and one eIF4A-binding domain, is sufficient to support translation initiation from these IRESs. 43 This allows picornavirus RNAs to compete effectively for the host translation machinery following infection, although the situation appears to be more complicated than this (see Section III). abstract: Viruses do not carry their own protein biosynthesis machinery and the translation of viral proteins therefore requires that the virus usurps the machinery of the host cell. To allow optimal translation of viral proteins at the expense of cellular proteins, virus families have evolved a variety of methods to repress the host translation machinery, while allowing effective viral protein synthesis. Many viruses use noncanonical mechanisms that permit translation of their own RNAs under these conditions. Viruses have also developed mechanisms to evade host innate immune responses that would repress translation under conditions of viral infection, in particular PKR activation in response to double-stranded RNA (dsRNA). Importantly, the study of viral translation mechanisms has enormously enhanced our understanding of many aspects of the cellular protein biosynthesis pathway and its components. A number of unusual mechanisms of translation initiation that were first discovered in viruses have since been observed in cellular mRNAs, and it has become apparent that a diverse range of translation mechanisms operates in eukaryotes, allowing subtle regulation of this essential process. url: https://api.elsevier.com/content/article/pii/S1877117309900096 doi: 10.1016/s1877-1173(09)90009-6 id: cord-329844-w969lczb author: Robson, B. title: Bioinformatics studies on a function of the SARS-CoV-2 spike glycoprotein as the binding of host sialic acid glycans date: 2020-06-08 words: 15903.0 sentences: 664.0 pages: flesch: 49.0 cache: ./cache/cord-329844-w969lczb.txt txt: ./txt/cord-329844-w969lczb.txt summary: The location of any sialic acid glycan binding region of SARS-CoV-2 is, a priori unclear, although intuitively (a) it would likely be associated with the cap or knob at the outer end of the spike protein, or (b) at least not involve exactly the same domain as is required for other important functions. An algorithm for predicting the domains and proteins involved in sialic acid glycan binding is developed in the course of the project described in Results Section 4, but this is primarily of a highly empirical nature. This, plus a sequence rather than three dimensional structure perspective, and a specific focus on binding sialic acid glycans rather than sugars in general, resulted in a substantial difference in scores from another major method of predicting sugar binding regions of proteins also discussed later below. abstract: SARS-CoV and SARS-CoV-2 do not appear to have functions of a hemagglutinin and neuraminidase. This is a mystery, because sugar binding activities appear essential to many other viruses including influenza and even most other coronaviruses in order to bind to and escape from the glycans (sugars, oligosaccharides or polysaccharides) characteristic of cell surfaces and saliva and mucin. The S1 N terminal Domains (S1-NTD) of the spike protein, largely responsible for the bulk of the characteristic knobs at the end of the spikes of SARS-CoV and SARS-CoV-2, are here predicted to be “hiding” sites for recognizing and binding glycans containing sialic acid. This may be important for infection and the ability of the virus to locate ACE2 as its known main host cell surface receptor, and if so it becomes a pharmaceutical target. It might even open up the possibility of an alternative receptor to ACE2. The prediction method developed, which uses amino acid residue sequence alone to predict domains or proteins that bind to sialic acids, is naïve, and will be advanced in future work. Nonetheless, it was surprising that such a very simple approach was so useful, and it can easily be reproduced in a very few lines of computer program to help make quick comparisons between SARS-CoV-2 sequences and to consider the effects of viral mutations. url: https://www.ncbi.nlm.nih.gov/pubmed/32658736/ doi: 10.1016/j.compbiomed.2020.103849 id: cord-333262-xvfl7ycj author: Robson, B. title: COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance date: 2020-04-11 words: 21671.0 sentences: 953.0 pages: flesch: 50.0 cache: ./cache/cord-333262-xvfl7ycj.txt txt: ./txt/cord-333262-xvfl7ycj.txt summary: The Wuhan and related isolates revealed a coronavirus that resides in the subgenus Sarbecovirus of the genus Betacoronavirus [2] , and although genetically distinct from its predecessor SARS-CoV it appeared to have similar external binding proteins, meaning here the spike glycoprotein discussed extensively in the present paper. In brief summary, the justifications for the ensemble pharmacophore in the coronavirus case, i.e. the contributions to "fuzziness", include parsimony, that proteins and parts of proteins sometimes have more than one function [12] encouraged by limited numbers of accessible sites (due to e.g. glycosylation) and exemplified by parallel alternative mechanisms of cell entry, multiple methods of drug action, escape from scientific defense measures by virus mutation, polymorphism of human proteins involved, different expression levels of human proteins involved, and the potential problem of the "specter of vaccine development" (concerns about missing the appropriate region of the virus that allows common cold viruses to escape the appropriate immune response). abstract: Abstract This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2′ spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles’ Heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding studies. The enzyme 11β-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets. url: https://doi.org/10.1016/j.compbiomed.2020.103749 doi: 10.1016/j.compbiomed.2020.103749 id: cord-276966-wmelyonk author: Roe, Kevin title: A proposed treatment for pathogenic enveloped viruses having high rates of mutation or replication date: 2020-07-08 words: 5242.0 sentences: 242.0 pages: flesch: 44.0 cache: ./cache/cord-276966-wmelyonk.txt txt: ./txt/cord-276966-wmelyonk.txt summary: In targeting specific viral pathogens, dual-protein ligand masks (for brevity, henceforth called dualprotein ligands) should be able to create a quick and powerful immune memory response with existing memory immune cells against some viral pathogens or virus infected cells, without some of the practical limitations of vaccines. Dual-protein ligands could induce an immune response by mimicking the key parts of antigens that activate existing immune memory cells or innate immune cells to attack tagged viral pathogens. All rights reserved One treatment option injects dual-protein ligands into the blood stream or localized regions to mask pathogenic surface proteins used by viruses to infect mammalian cells. Targeted dual-protein ligands could mask viral surface proteins to quickly treat some untreatable virus infections by using already existing immune cells. abstract: Several enveloped viruses, particularly some RNA viruses, have high rates of mutation or replication, which can make them virulent pathogens in humans and other mammals. A proposed treatment could use synthesized proteins to mask pathogenic viral surface proteins to quickly induce an immune attack on specific enveloped viruses by using existing immune cells. One treatment could inject dual‐protein ligand masks into patients' blood streams to mask pathogenic surface proteins used to infect mammalian cells. The mammalian immune system already uses an analogous, more complex structure called a pentraxin to neutralize some pathogens by connecting their surface proteins to immune cells. And several types of antiviral peptides have already experimentally demonstrated effectiveness in blocking various viral pathogen infections. These treatments offer advantages, especially for currently untreatable viral pathogens. Furthermore, using dual‐protein ligands and the antigenic memory of some subpopulations of NK cells would also allow the creation of defacto vaccines based on a host's NK cells, instead of vaccines utilizing CD4 and CD8 α:β T cells, which are limited by the requirement of MHC presentation of the target antigens to α:β T cells. Targeted NK cell vaccines could attack host cells latently or actively infected by intracellular pathogens, even host cells having pathogen downregulated MHC antigen presentation. Eight postulates concerning the effects of pathogen mutation, or change in phenotype from genetic recombination or rearrangement, and replication rates on pathogen versus host dominance are also listed, which should be applicable to viral and non‐viral pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/32640050/ doi: 10.1111/sji.12928 id: cord-341324-f9g9gitn author: Rojas, José M. title: Viral pathogen-induced mechanisms to antagonize mammalian interferon (IFN) signaling pathway date: 2020-10-21 words: 10837.0 sentences: 595.0 pages: flesch: 42.0 cache: ./cache/cord-341324-f9g9gitn.txt txt: ./txt/cord-341324-f9g9gitn.txt summary: This includes for instance cooperating in PRR recognition of viral PAMPs, stabilizing signaling complexes to improve their resistance to degradation, stopping virus entry, blocking viral capsid formation, impairing trafficking and budding of virions from the infected cells, but also modulating the IFN response to avoid the toxicity of these potent immune mediators. The phosphorylated STAT1/STAT2 heterodimer associates with interferon regulatory factor 9 (IRF9) to form the transcriptional factor complex ISGF3, which translocate to the nucleus and binds the IFN-response elements (ISRE) in ISG promoters leading to the expression of ISG products [36] (Fig. 2 The oligoadenylate synthetase (OAS)-latent RNase (RNase L) pathway is another IFN-inducible pathway that provides the cell with an effector mechanism upon recognition of viral dsRNA (reviewed in [44] ). abstract: Antiviral responses of interferons (IFNs) are crucial in the host immune response, playing a relevant role in controlling viralw infections. Three types of IFNs, type I (IFN-α, IFN-β), II (IFN-γ) and III (IFN-λ), are classified according to their receptor usage, mode of induction, biological activity and amino acid sequence. Here, we provide a comprehensive review of type I IFN responses and different mechanisms that viruses employ to circumvent this response. In the first part, we will give an overview of the different induction and signaling cascades induced in the cell by IFN-I after virus encounter. Next, highlights of some of the mechanisms used by viruses to counteract the IFN induction will be described. And finally, we will address different mechanism used by viruses to interference with the IFN signaling cascade and the blockade of IFN induced antiviral activities. url: https://www.ncbi.nlm.nih.gov/pubmed/33084946/ doi: 10.1007/s00018-020-03671-z id: cord-306733-df36w6l7 author: Rosales-Mendoza, Sergio title: What Does Plant-Based Vaccine Technology Offer to the Fight against COVID-19? date: 2020-04-14 words: 8591.0 sentences: 420.0 pages: flesch: 39.0 cache: ./cache/cord-306733-df36w6l7.txt txt: ./txt/cord-306733-df36w6l7.txt summary: Transient nuclear genome transformation Rapid production; high productivity; implemented at the industrial level Seed bank cannot be generated; requires purification of the antigen to eliminate toxic compounds from the host and ag-robacteria residues S protein; multiepitope vaccines A chimeric protein of GFP and amino acids 1-658 of the SARS-CoV-1 S protein (S1:GFP) was transiently expressed in tobacco leaves and stably transformed in tobacco and lettuce. No immunization assays were performed The SARS-CoV-1 N protein was transiently expressed in Nicotiana benthamiana, which induced in mice high levels of IgG1 and IgG2a and up regulation of IFN-γ and IL-10 in splenocytes. The precedents of SARS-CoV-1 and MERS antigens expressed in recombinant systems leading to the formation of VLPs constitute important guides for the topic of COVID-19 vaccine development. Thus, VLPs based on the main SARS-CoV-2 structural proteins is an attractive approach for vaccine development against coronavirus infections. abstract: The emergence of new pathogenic viral strains is a constant threat to global health, with the new coronavirus strain COVID-19 as the latest example. COVID-19, caused by the SARS-CoV-2 virus has quickly spread around the globe. This pandemic demands rapid development of drugs and vaccines. Plant-based vaccines are a technology with proven viability, which have led to promising results for candidates evaluated at the clinical level, meaning this technology could contribute towards the fight against COVID-19. Herein, a perspective in how plant-based vaccines can be developed against COVID-19 is presented. Injectable vaccines could be generated by using transient expression systems, which offer the highest protein yields and are already adopted at the industrial level to produce VLPs-vaccines and other biopharmaceuticals under GMPC-processes. Stably-transformed plants are another option, but this approach requires more time for the development of antigen-producing lines. Nonetheless, this approach offers the possibility of developing oral vaccines in which the plant cell could act as the antigen delivery agent. Therefore, this is the most attractive approach in terms of cost, easy delivery, and mucosal immunity induction. The development of multiepitope, rationally-designed vaccines is also discussed regarding the experience gained in expression of chimeric immunogenic proteins in plant systems. url: https://www.ncbi.nlm.nih.gov/pubmed/32295153/ doi: 10.3390/vaccines8020183 id: cord-282859-uxltqopq author: Rosati, A title: BAG3: a multifaceted protein that regulates major cell pathways date: 2011-04-07 words: 4431.0 sentences: 258.0 pages: flesch: 43.0 cache: ./cache/cord-282859-uxltqopq.txt txt: ./txt/cord-282859-uxltqopq.txt summary: These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. By modulating these pathways, BAG3 appears to mediate cell adaptive responses to stressful stimuli, and its alterations result in altered homeostasis and reduced cytoprotection, explaining why its expression is often found deregulated in a vast series of tumors. 12, 19 In humans, bag3 gene expression is constitutive in myocytes, a few other normal cell types and several primary tumors or tumor cell lines (lymphoid or myeloid leukemias, lymphomas, myeloma, neuroblastoma, pancreas, thyroid, breast and prostate carcinomas, melanoma, osteosarcoma, kidney, colon and ovary cancers, glioblastoma). 67 Similarly to what we described above for apoptosis, the ability of BAG3 to regulate cell adhesion appears to rely on multiple interactions of this protein through different structural domains. abstract: Bcl2-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that interacts with the ATPase domain of the heat shock protein (Hsp) 70 through BAG domain (110–124 amino acids). BAG3 is the only member of the family to be induced by stressful stimuli, mainly through the activity of heat shock factor 1 on bag3 gene promoter. In addition to the BAG domain, BAG3 contains also a WW domain and a proline-rich (PXXP) repeat, that mediate binding to partners different from Hsp70. These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. In normal cells, BAG3 is constitutively present in a very few cell types, including cardiomyocytes and skeletal muscle cells, in which the protein appears to contribute to cell resistance to mechanical stress. A growing body of evidence indicate that BAG3 is instead expressed in several tumor types. In different tumor contexts, BAG3 protein was reported to sustain cell survival, resistance to therapy, and/or motility and metastatization. In some tumor types, down-modulation of BAG3 levels was shown, as a proof-of-principle, to inhibit neoplastic cell growth in animal models. This review attempts to outline the emerging mechanisms that can underlie some of the biological activities of the protein, focusing on implications in tumor progression. url: https://www.ncbi.nlm.nih.gov/pubmed/21472004/ doi: 10.1038/cddis.2011.24 id: cord-270273-a4iu9qg6 author: Ruiz, Federico M. title: Chicken GRIFIN: Structural characterization in crystals and in solution date: 2017-12-15 words: 8271.0 sentences: 386.0 pages: flesch: 48.0 cache: ./cache/cord-270273-a4iu9qg6.txt txt: ./txt/cord-270273-a4iu9qg6.txt summary: The case study on galectins (b-galactoside-binding proteins with b-sandwich fold and a sequence signature responsible for ligand contact [5] ) is describing such a network with overlapping and distinct expression profiles [6e8]. In this study, the availability of crystals of the same protein obtained at different conditions documents the very low degree of influence of the pH value on the galectin fold, with some variability in unit cell Looking closely at the interface region between the two subunits of C-GRIFIN''s homodimer, it is established by the F1/S1 strands from the N-and C-termini of each subunit in the homodimer (residues 4e14/127-136) (Fig. 4B) . Taking analysis of C-GRIFIN and lactose binding again to the level of a solution in this report, measuring extent and profile of HDX in the absence and presence of ligand can identify the contact site. abstract: Despite its natural abundance in lenses of vertebrates the physiological function(s) of the galectin-related inter-fiber protein (GRIFIN) is (are) still unclear. The same holds true for the significance of the unique interspecies (fish/birds vs mammals) variability in the capacity to bind lactose. In solution, ultracentrifugation and small angle X-ray scattering (at concentrations up to 9 mg/mL) characterize the protein as compact and stable homodimer without evidence for aggregation. The crystal structure of chicken (C-)GRIFIN at seven pH values from 4.2 to 8.5 is reported, revealing compelling stability. Binding of lactose despite the Arg71Val deviation from the sequence signature of galectins matched the otherwise canonical contact pattern with thermodynamics of an enthalpically driven process. Upon lactose accommodation, the side chain of Arg50 is shifted for hydrogen bonding to the 3-hydroxyl of glucose. No evidence for a further ligand-dependent structural alteration was obtained in solution by measuring hydrogen/deuterium exchange mass spectrometrically in peptic fingerprints. The introduction of the Asn48Lys mutation, characteristic for mammalian GRIFINs that have lost lectin activity, lets labeled C-GRIFIN maintain capacity to stain tissue sections. Binding is no longer inhibitable by lactose, as seen for the wild-type protein. These results establish the basis for detailed structure-activity considerations and are a step to complete the structural description of all seven members of the galectin network in chicken. url: https://www.ncbi.nlm.nih.gov/pubmed/29248541/ doi: 10.1016/j.biochi.2017.12.003 id: cord-274080-884x48on author: Rumlová, Michaela title: In vitro methods for testing antiviral drugs date: 2018-06-30 words: 17989.0 sentences: 941.0 pages: flesch: 41.0 cache: ./cache/cord-274080-884x48on.txt txt: ./txt/cord-274080-884x48on.txt summary: For the majority of animal viruses, the activation of these fusion or penetration mechanisms occurs through conformational changes and structural rearrangements in viral surface proteins and/or the whole virion shell that may destabilize the capsid core. D: Three mechanisms (I.-III.) of DNA viruses replication are shown: (I): Following entry and uncoating, the DNA genome is transported to the nucleus; products of early genes (regulatory proteins, transcription factors) regulate the synthesis of viral enzymes (e.g. DNA polymerase) required for genome replication; expression of late genes encoding structural capsid proteins in the cytosol, they are then transported into nucleus where packaging and pre-assembly take place; preassembled procapsids exit the nucleus and leave the cell (e.g. Herpesviruses). Here, we provide an overview of in vitro methods, including cell-based assays, that may be suitable for screening of antivirotics that interfere with the key steps of viral life cycles and target either virus or cell-encoded proteins required for the infectivity. abstract: Abstract Despite successful vaccination programs and effective treatments for some viral infections, humans are still losing the battle with viruses. Persisting human pandemics, emerging and re-emerging viruses, and evolution of drug-resistant strains impose continuous search for new antiviral drugs. A combination of detailed information about the molecular organization of viruses and progress in molecular biology and computer technologies has enabled rational antivirals design. Initial step in establishing efficacy of new antivirals is based on simple methods assessing inhibition of the intended target. We provide here an overview of biochemical and cell-based assays evaluating the activity of inhibitors of clinically important viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/29292156/ doi: 10.1016/j.biotechadv.2017.12.016 id: cord-018018-2yyv8vuy author: Rybicki, Ed title: History and Promise of Plant-Made Vaccines for Animals date: 2018-07-04 words: 9127.0 sentences: 314.0 pages: flesch: 37.0 cache: ./cache/cord-018018-2yyv8vuy.txt txt: ./txt/cord-018018-2yyv8vuy.txt summary: 1995) was also used to demonstrate the efficacy of two very different plant-made papillomavirus vaccines, a few years after the demonstration that Human papillomavirus L1 major capsid protein virus-like particles could be produced in transgenic tobacco or potato (Biemelt et al. The early historical account of molecular farming for veterinary vaccines given above gives an idea of the array of technologies available and used up to the mid-2000s: transgenic and transplastomic expression of subunit proteins; recombinant plant viruses either used to express whole vaccine candidate genes, or to display chosen peptides fused to their capsid proteins; fusion of vaccine protein genes to carrier proteins to improve immunogenicity, including by inherent adjuvant properties; candidate parenteral and oral vaccines to both viruses and bacteria; therapeutics for animals made in plants; use of plant cell cultures to make antigens. abstract: Plant-made vaccines are now a well-established and well-tested concept in veterinary medicine—yet the only product so far licenced was never produced commercially. This is puzzling, given the breadth of exploration of plant-made animal vaccines, and their immunogenicity and efficacy, over more than twenty years of research. The range of candidate vaccines that have been tested in laboratory animal models includes vaccines for E. coli, Salmonella, Yersinia pestis, foot and mouth disease virus, rabbit haemorrhagic disease virus, rabbit and canine and bovine papillomaviruses, mink enteritis and porcine circovirus, and lately also bluetongue virus, among many others. There are many proofs of efficacy of such vaccines, and regulatory pathways appear to have been explored for their licencing. This review will briefly explore the history of plant-made vaccines for use in animals, and will discuss the unique advantages of plant-made vaccines for use in a veterinary medicine setting in detail, with a proposal of their relevance within the “One Health” paradigm. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122757/ doi: 10.1007/978-3-319-90137-4_1 id: cord-292985-w62xaa4f author: Römer, Rudolf A. title: Flexibility and mobility of SARS-CoV-2-related protein structures date: 2020-07-12 words: 5201.0 sentences: 341.0 pages: flesch: 61.0 cache: ./cache/cord-292985-w62xaa4f.txt txt: ./txt/cord-292985-w62xaa4f.txt summary: We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. 34 We have performed our analysis through multiple conformational steps starting from the crystal structures of SARS-CoV-2-related proteins as currently deposited in the PDB. In Fig. 1 (a) we see that for the crystal structure of SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain (PDB:6m3m), the largest rigid cluster in the pristine structure, i.e. at E cut = 0, largely remains rigid through the dilution process of consecutively lowering E cut values. Last, a protein with 2nd-order rigidity should have the most complex behaviour in terms of flexibility since new possible mobility can be expected throughout the range of E cut values. Moving along directions proposed by an elastic normal model analysis of the crystal structure, we can therefore construct possible motion trajectories that are fully consistent with the bond network and steric constraints. abstract: The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of SARS-CoV-2 drug targets, i.e. SARS-CoV-2 protein structures as deposited on the Protein Databank (PDB). We study their flexibility, rigidity and mobility, an important first step in trying to ascertain their dynamics for further drug-related docking studies. We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. For example, for the SARS-CoV-2 spike protein in the open configuration, our method identifies a possible further opening and closing of the S1 subunit through movement of SB domain. With full structural information of this process available, docking studies with possible drug structures are then possible in silico. In our study, we present full results for the more than 200 thus far published SARS-CoV-2-related protein structures in the PDB. url: https://doi.org/10.1101/2020.07.12.199364 doi: 10.1101/2020.07.12.199364 id: cord-355477-7xd93aqv author: SATIJA, NAMITA title: The Molecular Biology of SARS Coronavirus date: 2007-04-23 words: 4946.0 sentences: 279.0 pages: flesch: 52.0 cache: ./cache/cord-355477-7xd93aqv.txt txt: ./txt/cord-355477-7xd93aqv.txt summary: abstract: Severe acute respiratory syndrome (SARS) is the first emerging infectious disease of the 21st century that has been highly transmissible and fatal and was caused by a previously unknown coronavirus (SARS‐CoV). Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways Assembly of severe acute respiratory syndrome coronavirus RNA packaging signal into virus-like particles is nucleocapsid dependent Recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein forms a dimer through its C-terminal domain Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells abstract: abstract: Severe acute respiratory syndrome (SARS) is the first emerging infectious disease of the 21st century that has been highly transmissible and fatal and was caused by a previously unknown coronavirus (SARS‐CoV). The SARS epidemic in 2003 resulted in more than 8400 SARS cases and approximately 800 deaths. Existing in non‐identified animal reservoirs, SARS‐CoV continues to represent a threat to humans although more than four years have passed since a large outbreak of SARS, and no new cases have been reported. However, we cannot exclude the possibility of reemergence of SARS. It is hence necessary to understand the biology of the SARS‐CoV to deal adequately with the next outbreak, whenever it happens. The SARS‐CoV is a novel coronavirus with a large (∼30 thousand nucleotides) positive‐sense, single‐stranded RNA containing 14 functional open reading frames (ORFs) of which 2 large ORFs constitute the replicase gene which encodes proteins required for viral RNA syntheses. The remaining 12 ORFs encode the 4 structural proteins: spike, membrane, nucleocapsid and envelope; and eight accessory proteins. The viral genome and its expression within the host cell undergoes extensive translational and enzymatic processing to form the 4 structural, 8 accessory and 16 nonstructural proteins. In an effort to understand the molecular mechanisms or capsid assembly and viral pathogenesis, laboratories around the world have adopted a variety of approaches to answering these trivial questions. It has been our effort to consolidate all information known to date about the molecular mechanisms of the SARS‐CoV into this chapter to update our readership on the current status of research. url: https://www.ncbi.nlm.nih.gov/pubmed/17470909/ doi: 10.1196/annals.1408.002 id: cord-023726-2fduzqyb author: STRAUSS, JAMES H. title: The Structure of Viruses date: 2012-07-27 words: 10614.0 sentences: 633.0 pages: flesch: 57.0 cache: ./cache/cord-023726-2fduzqyb.txt txt: ./txt/cord-023726-2fduzqyb.txt summary: Also shown for each family is the presence or absence of an envelope in the virion, the triangulation number (defined later) if the virus is icosahedral, the morphology of the nucleocapsid or core, and figure numbers where the structures of members of a family are illustrated. Structural studies of viruses have shown that the capsid proteins that form the virions of many plant and animal icosahedral viruses have a common fold. The largest particle is the nucleocapsid of herpes simplex virus, which is 1250 Å in diameter and has T=16 symmetry (the virion is enveloped but only the nucleocapsid is regular FIGURE 2.5 Gallery of three-dimensional reconstructions of icosahedral viruses from cryoelectron micrographs. For most RNA viruses, nucleocapsids can be recognized as distinct structures within the infected cell and can be isolated from virions by treatment with detergents that dissolve the envelope. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173534/ doi: 10.1016/b978-0-12-373741-0.50005-2 id: cord-288673-ku3tmjd3 author: Sabotič, Jerica title: Microbial and fungal protease inhibitors—current and potential applications date: 2012-01-05 words: 14630.0 sentences: 689.0 pages: flesch: 29.0 cache: ./cache/cord-288673-ku3tmjd3.txt txt: ./txt/cord-288673-ku3tmjd3.txt summary: Because proteases play essential roles in life and death processes in all living organisms and because peptide bond hydrolysis is irreversible, anomalies in proteolytic activities lead to numerous pathological conditions, including cancer, neurodegenerative disorders and inflammatory and cardiovascular diseases, as well as bacterial, viral and parasitic diseases (Lopez-Otin and Bond 2008; Turk 2006) . Another important oral cavity pathogen involved in periodontal disease, Porphyromonas gingivalis, in addition to a few cysteine proteases (discussed further in the following), produces a serine protease, a prolyl tripeptidyl peptidase PtpA (family S9), which is involved in degrading host connective tissue, providing nutrients for bacterial growth (Banbula et al. Several proteases of the serine catalytic type have also been targeted for the design of specific protease inhibitors for use in cancer treatment, including the urokinase plasminogen activator and matriptase (Abbenante and Fairlie 2005; Bialas and Kafarski 2009; Ulisse et al. abstract: Proteolytic enzymes play essential metabolic and regulatory functions in many biological processes and also offer a wide range of biotechnological applications. Because of their essential roles, their proteolytic activity needs to be tightly regulated. Therefore, small molecules and proteins that inhibit proteases can be versatile tools in the fields of medicine, agriculture and biotechnology. In medicine, protease inhibitors can be used as diagnostic or therapeutic agents for viral, bacterial, fungal and parasitic diseases as well as for treating cancer and immunological, neurodegenerative and cardiovascular diseases. They can be involved in crop protection against plant pathogens and herbivorous pests as well as against abiotic stress such as drought. Furthermore, protease inhibitors are indispensable in protein purification procedures to prevent undesired proteolysis during heterologous expression or protein extraction. They are also valuable tools for simple and effective purification of proteases, using affinity chromatography. Because there are such a large number and diversity of proteases in prokaryotes, yeasts, filamentous fungi and mushrooms, we can expect them to be a rich source of protease inhibitors as well. url: https://doi.org/10.1007/s00253-011-3834-x doi: 10.1007/s00253-011-3834-x id: cord-286301-7sjw5ci7 author: Sadasivan, Jibin title: Cytoplasmic tail of coronavirus spike protein has intracellular targeting signals date: 2017-04-18 words: 6243.0 sentences: 289.0 pages: flesch: 48.0 cache: ./cache/cord-286301-7sjw5ci7.txt txt: ./txt/cord-286301-7sjw5ci7.txt summary: SARS-S-Y was absent from surface in most of the cells and localized at the intracellular compartments (figure 5a), and OC43-S protein was mainly localized in distinct puncta that could represent endocytic structures following internalization from the plasma membrane (figure 5b). Our studies clearly demonstrated that the KXHXX motif is the major intracellular localization signal of the full-length SARS-S protein and the C-terminal proximity is not essential. Our alanine mutation studies on the KXHXX motif confirm the importance of the lysine and histidine in the full-length wild-type HCoV-SARS S protein; the mutant protein showed localization in plasma membrane instead of the usual ER and ERGIC. In contrast, Lysosomal acid phosphatase, also a type I membrane protein with a cytosolic tail GYXXØ motif located 7 residues from both transmembrane domain and the carboxy termini (Tm-RMQAQPPGYRHVADGEDHA) delivered mainly via the cell surface (Braun et al. abstract: Intracellular trafficking and localization studies of spike protein from SARS and OC43 showed that SARS spike protein is localized in the ER or ERGIC compartment and OC43 spike protein is predominantly localized in the lysosome. Differential localization can be explained by signal sequence. The sequence alignment using Clustal W shows that the signal sequence present at the cytoplasmic tail plays an important role in spike protein localization. A unique GYQEL motif is identified at the cytoplasmic terminal of OC43 spike protein which helps in localization in the lysosome, and a novel KLHYT motif is identified in the cytoplasmic tail of SARS spike protein which helps in ER or ERGIC localization. This study sheds some light on the role of cytoplasmic tail of spike protein in cell-to-cell fusion, coronavirus host cell fusion and subsequent pathogenicity. url: https://www.ncbi.nlm.nih.gov/pubmed/28569247/ doi: 10.1007/s12038-017-9676-7 id: cord-020757-q4ivezyq author: Saikumar, Pothana title: Apoptosis and Cell Death: Relevance to Lung date: 2010-05-21 words: 7402.0 sentences: 420.0 pages: flesch: 39.0 cache: ./cache/cord-020757-q4ivezyq.txt txt: ./txt/cord-020757-q4ivezyq.txt summary: The extrinsic pathway involves binding of death ligands such as tumor necrosis factor-α (TNF-α), CD95 ligand (Fas ligand), and TNF-related apoptosis-inducing ligand (TRAIL) to their cognate cell surface receptors TNFR1, CD95/Fas, TRAIL-R1, TRAIL-R2, and the DR series of receptors, 29 resulting in the activation of initiator caspase-8 (also known as FADD-homologous ICE/CED-3-like protease or FLICE) and subsequent activation of effector caspase-3 ( Figure 4 .2). In cytotoxic T lymphocyte-induced death, granzyme B, which enters the cell through membrane channels formed by the protein perforin, activates caspases by cleaving them directly or indirectly. Intracellular Pathways: Lack of survival stimuli (withdrawal of growth factor, hypoxia, genotoxic substances, etc.) is thought to generate apoptotic signals through ill-defi ned mechanisms, which lead to translocation of proapoptotic proteins such as Bax to the outer mitochondrial membrane. For example, agents that damage DNA, such as ionizing radiation and certain xenobiotics, lead to activation of p53-mediated mechanisms that commit cells to apoptosis, at least in part through transcriptional upregulation of proapoptotic proteins. abstract: In multicellular organisms, cell death plays an important role in development, morphogenesis, control of cell numbers, and removal of infected, mutated, or damaged cells. The term apoptosis was first coined in 1972 by Kerr et al.1 to describe the morphologic features of a type of cell death that is distinct from necrosis and is today considered to represent programmed cell death. In fact, the evidence that a genetic program existed for physiologic cell death came from the developmental studies of the nematode Caenorhabditis elegans.2 As time has progressed, however, apoptotic cell death has been shown to occur in many cell types under a variety of physiologic and pathologic conditions. Cells dying by apoptosis exhibit several characteristic morphologic features that include cell shrinkage, nuclear condensation, membrane blebbing, nuclear and cellular fragmentation into membrane-bound apoptotic bodies, and eventual phagocytosis of the fragmented cell (Figure 4.1). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147438/ doi: 10.1007/978-0-387-72430-0_4 id: cord-048471-7jszm1nd author: Salim, Omar title: Functional Analysis of the 5′ Genomic Sequence of a Bovine Norovirus date: 2008-05-14 words: 5646.0 sentences: 246.0 pages: flesch: 49.0 cache: ./cache/cord-048471-7jszm1nd.txt txt: ./txt/cord-048471-7jszm1nd.txt summary: Although slightly larger than predicted the N-term protein was detected in a processed form in vivo, thus not only demonstrating initial translation of the ORF1 polyprotein but also activity of the viral protease. Previous studies of norovirus polyprotein processing have yielded three major products following in vitro transcription and translation, representing the uncleaved 3ABCD, N-term and 2C proteins. In addition, this important observation also confirms for the first time that the JV 3C protease was active in cells transfected with capped RNA as the size of the V5/N-term indicated successful cleavage of the protein from the ORF1 polyprotein. Unlike similarly studied human noroviruses JV initially did not appear to express the N-terminal protein, presenting the possibility that the encoding RNA sequence had a regulatory function itself, most likely involved in translation initiation in an IRES-like manner. abstract: BACKGROUND: Jena Virus (JV), a bovine Norovirus, causes enteric disease in cattle and represents a potential model for the study of enteric norovirus infection and pathogenesis. The positive sense RNA genome of JV is organised into ORF1 (non-structural proteins), ORF2 (major capsid protein) and ORF3 (minor capsid protein). The lack of a cell culture system for studying JV replication has meant that work to date has relied upon in vitro systems to study non-structural protein synthesis and processing. PRINCIPAL FINDINGS: Only two of the three major ORF1 proteins were identified (p110 and 2C) following in vitro translation of JV RNA, the N-term protein was not detected. The N-term encoding genomic sequence (5′GS) was tested for IRES-like function in a bi-cistronic system and displayed no evidence of IRES-like activity. The site of translation initiation in JV was determined to be at the predicted nucleotide 22. Following the insertion of an epitope within the 5′GS the JV N-term protein was identified in vitro and within RNA transfected cells. CONCLUSIONS: The in vitro transcription/translation system is currently the best system for analysing protein synthesis and processing in JV. Unlike similarly studied human noroviruses JV initially did not appear to express the N-terminal protein, presenting the possibility that the encoding RNA sequence had a regulatory function, most likely involved in translation initiation in an IRES-like manner. This was not the case and, following determination of the site of translation initiation the N-term protein was detected using an epitope tag, both in vitro and in vivo. Although slightly larger than predicted the N-term protein was detected in a processed form in vivo, thus not only demonstrating initial translation of the ORF1 polyprotein but also activity of the viral protease. These findings indicate that the block to noroviral replication in cultured cells lies elsewhere. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364642/ doi: 10.1371/journal.pone.0002169 id: cord-319517-denczc6t author: Salipalli, Sandeep title: Recent advances in live cell imaging of hepatoma cells date: 2014-07-08 words: 9184.0 sentences: 433.0 pages: flesch: 46.0 cache: ./cache/cord-319517-denczc6t.txt txt: ./txt/cord-319517-denczc6t.txt summary: This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. The success of live cell imaging relies on various factors including the specific imaging system, climate controlling devices for cultured cells under investigation, construction of recombinant plasmid DNA, transfer and expression of candidate genes and/or fluorescent proteins in mammalian cells. T4SS (Bartonella sp.) 60-70% 50% >70% >60% 50-60% [76] [77] [78] lipofection (1 μg) methods were used for transfection of plasmid encoding fluorescent protein (pEGFP and pEYFP) tagged to human and mouse ADRP genes in Huh-7 cells as to study the pathways of lipid droplet metabolism. abstract: Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the availability of advanced optical devices and improved cell culture protocols it has become a rapidly growing research methodology. The success of this technique relies mainly on the selection of suitable reporter proteins, construction of recombinant plasmids possessing cell type specific promoters as well as reliable methods of gene transfer. This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. Moreover, different expression systems of marker proteins and the modes of gene transfer are discussed with emphasis on the study of lipid droplet formation in hepatocytes as an example. url: https://doi.org/10.1186/1471-2121-15-26 doi: 10.1186/1471-2121-15-26 id: cord-318853-mxyxwkhx author: Sallie, Richard title: Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases date: 2005-08-22 words: 10541.0 sentences: 396.0 pages: flesch: 25.0 cache: ./cache/cord-318853-mxyxwkhx.txt txt: ./txt/cord-318853-mxyxwkhx.txt summary: Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. Hence, as relative concentrations of wild-type and variant viral proteins vary, alteration of both processivity and fidelity of RNA pol results, permitting viruses to adaptively respond to environmental changes, including immune recognition and reaction to evolving cell receptors. As clear evidence exists for viral disruption of leptin function [106] and virus-associated weight gain in humans [107] and monkeys [108] , is it possible the global epidemics of type II diabetes mellitus, insulin resistance, hyperlipidaemia and obesity now prevalent [109] [110] [111] [112] [113] [114] [115] [116] , are just that; epidemics fundamentally caused by viruses that co-opt insulin or leptin or other associated receptors for cell access and generate protein quasispecies that disrupt receptor function? abstract: Much of the worlds' population is in active or imminent danger from established infectious pathogens, while sporadic and pandemic infections by these and emerging agents threaten everyone. RNA polymerases (RNA(pol)) generate enormous genetic and consequent antigenic heterogeneity permitting both viruses and cellular pathogens to evade host defences. Thus, RNA(pol )causes more morbidity and premature mortality than any other molecule. The extraordinary genetic heterogeneity defining viral quasispecies results from RNA(pol )infidelity causing rapid cumulative genomic RNA mutation a process that, if uncontrolled, would cause catastrophic loss of sequence integrity and inexorable quasispecies extinction. Selective replication and replicative homeostasis, an epicyclical regulatory mechanism dynamically linking RNApol fidelity and processivity with quasispecies phenotypic diversity, modulating polymerase fidelity and, hence, controlling quasispecies behaviour, prevents this happening and also mediates immune escape. Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. This mechanism – "Viral Receptor Disease (VRD)" – may explain so-called "viral autoimmunity", some classical autoimmune disorders and other diseases, including type II diabetes mellitus, and some forms of obesity. Viral receptor disease is a unifying hypothesis that may also explain some diseases with well-established, but multi-factorial and apparently unrelated aetiologies – like coronary artery and other vascular diseases – in addition to diseases like schizophrenia that are poorly understood and lack plausible, coherent, pathogenic explanations. url: https://www.ncbi.nlm.nih.gov/pubmed/16115320/ doi: 10.1186/1743-422x-2-70 id: cord-033333-880jx1bt author: Salman, Saad title: In silico analysis of protein/peptide-based inhalers against SARS-CoV-2 date: 2020-10-08 words: 3431.0 sentences: 226.0 pages: flesch: 53.0 cache: ./cache/cord-033333-880jx1bt.txt txt: ./txt/cord-033333-880jx1bt.txt summary: The molecular docking was performed for these inhalers including human neutralizing S230 light chain-antibody (monoclonal antibodies [mAbs]), alpha-1-antitrypsin (AAT), short-palate-lung and nasal-epithelial clone-1-derived peptides (SPLUNC1) and dornase-alfa (DA) against spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to assess their inhibitory activity. Protein-protein interaction (PPI) of COVID-19 spike glycoprotein with alpha-1-antitrypsin (1atu), dornase-alfa (4AWN), angiotensin-converting enzyme-2 (ACE-2) (PDB ID:1R4L), human palate, lung and nasal epithelium clone protein (SPLUNC1) (4n4x) and human neutralizing the S230 light chain antibody was evaluated through HawkDock. We attempted to address this issue by analyzing a variety of protein/peptide-based inhalers/antimucolytic agents and previously utilized mAb (used in asthma) to observe their possible interaction with the SARS-CoV-2 spike protein. • Molecular docking analysis of protein/peptide-based inhalers revealed that the S230 light chain antibody and dornase-alfa demonstrated a strong affinity for SARS-CoV-2 spike protein. abstract: Aim: Peptide/protein-based inhalers are excessively used to treat respiratory disorders. The molecular docking was performed for these inhalers including human neutralizing S230 light chain-antibody (monoclonal antibodies [mAbs]), alpha-1-antitrypsin (AAT), short-palate-lung and nasal-epithelial clone-1-derived peptides (SPLUNC1) and dornase-alfa (DA) against spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to assess their inhibitory activity. Materials & methods: HawkDock was used to dock these biologics against SARS-CoV-2 spike-glycoprotein. Results: Results showed that DA, AAT and mAb were quite active against spike glycoprotein with a binding free energy of -26.35 and -22.94 kcal/mol. Conclusion: mAB and AAT combined with DA can be used in the treatment of coronavirus disease of 2019 as a potential anti-SARS-CoV-2 agent. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543042/ doi: 10.2217/fvl-2020-0119 id: cord-304040-64obh7i3 author: Sande, Charles J. title: Untargeted analysis of the airway proteomes of children with respiratory infections using mass spectrometry based proteomics date: 2018-09-14 words: 5041.0 sentences: 250.0 pages: flesch: 43.0 cache: ./cache/cord-304040-64obh7i3.txt txt: ./txt/cord-304040-64obh7i3.txt summary: Our proteomic experiments tested the optimal approach to characterize airway proteome on swab samples eluted in UTM based on the number of proteins identified without BSA depletion (Total proteome: Protocol A) and with its depletion using a commercial kit; Allprep, Qiagen (cellular proteome: Protocol B, Ci, and Cii). Compared to previous mass-spectrometry-based proteomics studies of the upper airway, the number of proteins identified in protocol Cii, vastly exceeded the number of proteins reported in previously published reports 14, 20, 22, 23, 25, 26, 28, 29 . Further characterisation the proteomes identified in protocol Cii, was done by evaluating the expression levels of marker proteins of resident naso-oro-pharyngeal epithelial cells. In addition to these definitive upper-airway proteins, we found a consistently high level of expression of mucins (MUC1 & 5) -the main component of respiratory tract mucus -and mucosal-associated keratins, KRT4 and KRT13. Our search of T-cell associated marker and effector proteins, did not identify any such proteins in the upper-airway proteomes of any of the children in this study. abstract: The upper airway – which consists mainly of the naso- and oro-pharynx - is the first point of contact between the respiratory system and microbial organisms that are ubiquitous in the environment. It has evolved highly specialised functions to address these constant threats whilst facilitating seamless respiratory exchange with the lower respiratory tract. Dysregulation of its critical homeostatic and defence functions can lead to ingress of pathogens into the lower respiratory tract, potentially leading to serious illness. Systems-wide proteomic tools may facilitate a better understanding of mechanisms in the upper airways in health and disease. In this study, we aimed to develop a mass spectrometry based proteomics method for characterizing the upper airways proteome. Naso- and oropharyngeal swab samples used in all our experiments had been eluted in the Universal Transport Media (UTM) containing significantly high levels of bovine serum albumin. Our proteomic experiments tested the optimal approach to characterize airway proteome on swab samples eluted in UTM based on the number of proteins identified without BSA depletion (Total proteome: Protocol A) and with its depletion using a commercial kit; Allprep, Qiagen (cellular proteome: Protocol B, Ci, and Cii). Observations and lessons drawn from protocol A, fed into the design and implementation of protocol B, and from B to protocol Ci and finally Cii. Label free proteome quantification was used in Protocol A (n = 6) and B (n = 4) while commercial TMT 10plex reagents were used for protocols Ci and ii (n = 83). Protocols Ci and ii were carried out under similar conditions except for the elution gradient: 3 h and 6 h respectively. Swab samples tested in this study were from infants and children with and without upper respiratory tract infections from Kilifi County Hospital on the Kenyan Coast. Protocol A had the least number of proteins identified (215) while B produced the highest number of protein identifications (2396). When Protocol B was modified through sample multiplexing with TMT to enable higher throughput (Protocol Ci), the number of protein identified reduced to 1432. Modification of protocol Ci by increasing the peptide elution time generated Protocol Cii that substantially increased the number of proteins identified to 1875. The coefficient of variation among the TMT runs in Protocol Cii was <20%. There was substantial overlap in the identity of proteins using the four protocols. Our method was were able to identify marker proteins characteristically expressed in the upper airway. We found high expression levels of signature nasopharyngeal and oral proteins, including BPIFA1/2 and AMY1A, as well as a high abundance of proteins related to innate and adaptive immune function in the upper airway. We have developed a sensitive systems-level proteomic assay for the systematic quantification of naso-oro-pharyngeal proteins. The assay will advance mechanistic studies of respiratory pathology, by providing an untargeted and hypothesis-free approach of examining the airway proteome. url: https://doi.org/10.1038/s41598-018-32072-3 doi: 10.1038/s41598-018-32072-3 id: cord-270587-k56fze59 author: Scherbinina, Sofya I. title: Three-Dimensional Structures of Carbohydrates and Where to Find Them date: 2020-10-18 words: 12390.0 sentences: 819.0 pages: flesch: 34.0 cache: ./cache/cord-270587-k56fze59.txt txt: ./txt/cord-270587-k56fze59.txt summary: • Database can be freely accessed through web user interface; • Database must contain experimentally confirmed and/or predicted 3D structures (preprocessed and/or generated on-the-fly from a primary structure input) of glycans, glycoproteins, or protein-carbohydrate complexes; • Stored 3D structures must be deposited as atomic coordinates in PDB, MOL, or other format, and the structures must contain a saccharide moiety; • • Database can be freely accessed through web user interface; • Database must contain experimentally confirmed and/or predicted 3D structures (preprocessed and/or generated on-the-fly from a primary structure input) of glycans, glycoproteins, or protein-carbohydrate complexes; • Stored 3D structures must be deposited as atomic coordinates in PDB, MOL, or other format, and the structures must contain a saccharide moiety; • Currently, CHARMM36 parameterization features include monosaccharides in furanose [171] and pyranose [172] forms, glycosidic linkages between monosaccharides [171, 173] , complex carbohydrates and glycoproteins Detailed comparisons of all-chemical and dedicated force fields in a context of glycan modeling have been published [114, 139, 151, 167] . abstract: Analysis and systematization of accumulated data on carbohydrate structural diversity is a subject of great interest for structural glycobiology. Despite being a challenging task, development of computational methods for efficient treatment and management of spatial (3D) structural features of carbohydrates breaks new ground in modern glycoscience. This review is dedicated to approaches of chemo- and glyco-informatics towards 3D structural data generation, deposition and processing in regard to carbohydrates and their derivatives. Databases, molecular modeling and experimental data validation services, and structure visualization facilities developed for last five years are reviewed. url: https://doi.org/10.3390/ijms21207702 doi: 10.3390/ijms21207702 id: cord-003435-ke0az7nf author: Schlake, Thomas title: mRNA as novel technology for passive immunotherapy date: 2018-10-17 words: 15190.0 sentences: 850.0 pages: flesch: 40.0 cache: ./cache/cord-003435-ke0az7nf.txt txt: ./txt/cord-003435-ke0az7nf.txt summary: Recombinant technologies further expanded the available therapies based on mAbs. In vitro antibody selection technologies like phage or ribosome display were developed to enable the generation of highly specific human mAbs out of libraries that may even be naïve for the specific antigens [31] [32] [33] [34] [35] [36] 1 Schematic illustration comparing active immunization and passive antibody immunotherapies. While T cell engineering for adoptive transfer inevitably requires the use of nucleic acids encoding a target-specific receptor, antibody immunotherapy can deploy recombinant proteins. However, the effects of mRNA modifications on translation, immunostimulation and resulting protein expression appear to be variable, for instance dependent on the type of target cells. In comparison to a single transfer of cells with retroviral CAR expression, an mRNA-encoded receptor required three consecutive lymphocyte infusions to obtain a comparable antitumor effect [262] . abstract: While active immunization elicits a lasting immune response by the body, passive immunotherapy transiently equips the body with exogenously generated immunological effectors in the form of either target-specific antibodies or lymphocytes functionalized with target-specific receptors. In either case, administration or expression of recombinant proteins plays a fundamental role. mRNA prepared by in vitro transcription (IVT) is increasingly appreciated as a drug substance for delivery of recombinant proteins. With its biological role as transient carrier of genetic information translated into protein in the cytoplasm, therapeutic application of mRNA combines several advantages. For example, compared to transfected DNA, mRNA harbors inherent safety features. It is not associated with the risk of inducing genomic changes and potential adverse effects are only temporary due to its transient nature. Compared to the administration of recombinant proteins produced in bioreactors, mRNA allows supplying proteins that are difficult to manufacture and offers extended pharmacokinetics for short-lived proteins. Based on great progress in understanding and manipulating mRNA properties, efficacy data in various models have now demonstrated that IVT mRNA constitutes a potent and flexible platform technology. Starting with an introduction into passive immunotherapy, this review summarizes the current status of IVT mRNA technology and its application to such immunological interventions. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339677/ doi: 10.1007/s00018-018-2935-4 id: cord-020664-m47ejlsn author: Schlüter, Klaus-Dieter title: Intrakrine, parakrine und autokrine Funktionen des PTH/PTHrP-Systems date: 2006 words: 7814.0 sentences: 915.0 pages: flesch: 53.0 cache: ./cache/cord-020664-m47ejlsn.txt txt: ./txt/cord-020664-m47ejlsn.txt summary: Ein groûer Unterschied zwischen dem namensgebenden Peptid der Familie, PTH, und den beiden strukturverwandten Proteinen PTHrP und TIP39 ist, dass PTHrP und TIP39 hauptsåchlich auto-, para-oder intrakrin wirken, wohingegen die PTH-Effekte vorwiegend endokriner Natur sind. Demgegençber gibt es aber auch Untersuchungen, die zeigen, dass in der N-terminalen Region von PTH und PTHrP ebenfalls Sequenzen vorhanden sind, die den PLC/PKC-Signal-Weg aktivieren kaennen (Takasu et al. Aufgrund des Vorkommens von biologisch aktiven mittregionalen PTHrP-Fragmenten kann vermutet werden, dass fçr diese Teilpeptide auch entsprechende Rezeptoren existieren, da diese Peptide nicht in der Lage sind, mit dem klassischen PTH1R zu interagieren. Transgene Måuse, die entweder PTHrP oder aber PTH1R in den Glattmuskelzellen der Gefåûe çberexprimieren, sind hypotensiv und weisen eine gestaerte Reaktion bei Applikation von Vasodilatoren auf Qian et al. 1028±1035 a 1.6 Intrakrine, parakrine und autokrine Funktionen des PTH/PTHrP-Systems Nickols GA, Nana AD, Nickols MA, DiPette DJ, Asimakis GK (1989) Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144038/ doi: 10.1007/3-540-28782-5_6 id: cord-017326-1caeui30 author: Seay, Montrell title: Digesting Oneself and Digesting Microbes: Autophagy as a Host Response to Viral Infection date: 2005 words: 11363.0 sentences: 489.0 pages: flesch: 34.0 cache: ./cache/cord-017326-1caeui30.txt txt: ./txt/cord-017326-1caeui30.txt summary: Genetic studies in yeast and mammalian cells have also shown that the eIF2 kinase signaling pathway is required for starvation and herpes simplex virus-induced autophagy 18 . The role of some of the Atg proteins, including ones that act in the lipid kinase signaling complex and in the ubiquitin-like conjugation pathways, has been studied in plant and mammalian viral infections (see Table 1 ). Together, the studies of Sindbis virus infection in neurons overexpressing beclin 1 or in cultured cells lacking beclin 1 or atg5 demonstrate a role for mammalian autophagy genes in both restricting viral replication and in protection against virus-induced cell death. The interferon-inducible, antiviral PKR signaling pathway positively regulates autophagy, and both mammalian and plant autophagy genes restrict viral replication and protect against virus-induced cell death. The interferon-inducible, antiviral PKR signaling pathway positively regulates autophagy, and both mammalian and plant autophagy genes restrict viral replication and protect against virus-induced cell death. abstract: Although research in this area is still in a stage of infancy, it seems likely that the lysosomal degradation pathway of autophagy plays an evolutionarily conserved role in antiviral immunity. The interferon-inducible, antiviral PKR signaling pathway positively regulates autophagy, and both mammalian and plant autophagy genes restrict viral replication and protect against virus-induced cell death. Given this role of autophagy in innate immunity, it is not surprising that viruses have evolved numerous strategies to inhibit host autophagy. Different viral gene products can either modulate autophagy regulatory signals or directly interact with components of the autophagy execution machinery. Moreover, certain RNA viruses have managed to “co-apt” the autophagy pathway, selectively utilizing certain components of the dynamic membrane rearrangement system to promote their own replication inside the host cytoplasm. In addition to this newly emerging role of autophagy in innate immunity, autophagy plays an important role in many other fundamental biological processes, including tissue homeostasis, differentiation and development, cell growth control, and the prevention of aging. Accordingly, the inhibition of host autophagy by viral gene products has important implications not only for understanding mechanisms of immune evasion, but also for understanding novel mechanisms of viral pathogenesis. It will be interesting to dissect the role of viral inhibition of autophagy in acute, persistent, and latent viral replication, as well as in the pathogenesis of cancer and other medical diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121853/ doi: 10.1007/1-4020-3242-0_11 id: cord-266977-5swwc6kr author: Secker, Thomas.J. title: Journal of Hospital Infection A cold water, ultrasonic activated stream efficiently removes proteins and prion-associated amyloid from surgical stainless steel date: 2020-09-19 words: 4562.0 sentences: 241.0 pages: flesch: 44.0 cache: ./cache/cord-266977-5swwc6kr.txt txt: ./txt/cord-266977-5swwc6kr.txt summary: authors: Secker, Thomas.J.; Leighton, Timothy.G.; Offin, Douglas.G.; Birkin, Peter.R.; Hervé, Rodolphe.C.; Keevil, Charles.W. title: Journal of Hospital Infection A cold water, ultrasonic activated stream efficiently removes proteins and prion-associated amyloid from surgical stainless steel Aim: To test the efficacy of an ultrasonically activated stream for the removal of tissue 27 proteins, including prion-associated amyloid, from surgical stainless steel (SS) surfaces. This study has tested the efficacy of UAS technology for the removal of 239 total protein and prion-amyloid from stainless steel, which is considered the most difficult 240 contaminant to decontaminate in the surgical field. 335 J o u r n a l P r e -p r o o f Tissue protein (Dark grey bars) and prion-associated amyloid (light grey bars) attachment 545 from different prion-infected brain homogenates (22L, ME7 and 263K) to surgical stainless 546 steel pre and post treatment with an ultrasonically activated stream (UAS) (Graph A). abstract: BACKGROUND: Sterile Service Department decontamination procedures for surgical instruments struggle to demonstrate efficient removal of the hardiest infectious contaminants, such as prion proteins. A recently designed novel system, which utilises a low pressure ultrasonic activated, cold water stream, has previously demonstrated efficient hard surface cleaning of several biological contaminants. AIM: To test the efficacy of an ultrasonically activated stream for the removal of tissue proteins, including prion-associated amyloid, from surgical stainless steel (SS) surfaces. METHODS: Test surfaces were contaminated with 22L, ME7 or 263K prion infected brain homogenates. The surfaces were treated with the ultrasonically activated water stream for contact times of 5 and 10 seconds. Residual proteinaceous and amyloid contamination were quantified using sensitive microscopic analysis, and immunoblotting was used to characterize the eluted prion residues before and after treatment with the ultrasonically activated stream. FINDINGS: Efficient removal of the different prion strains from the surgical SS surfaces was observed, and reduced levels of protease sensitive and resistant prion protein was detected in recovered supernatant. CONCLUSIONS: This study demonstrated that an ultrasonically activated stream has the potential to be a cost-effective solution to improve current decontamination practices and has the potential to reduce hospital acquired infections. url: https://www.ncbi.nlm.nih.gov/pubmed/32956784/ doi: 10.1016/j.jhin.2020.09.021 id: cord-007211-prygoc0q author: Segawa, Hiroaki title: The Roles of Individual Cysteine Residues of Sendai Virus Fusion Protein in Intracellular Transport(1) date: 1998-06-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The role of intramolecular disulfide bonds in the fusion (F) protein of Sendai virus was studied. The 10 cysteine residues were changed to serine residues using site-directed mutagenesis. None of the cysteine mutant F proteins reacted with a monoclonal antibody specific for the mature conformation of the F protein, but eight of ten mutants reacted with an immature conformation-specific monoclonal antibody. The transport of these mutant proteins to the cell surface was drastically reduced. All of the cysteine mutant F proteins remained sensitive to endoglycosidase H (endo H) for 3 h after their synthesis. Moreover, cell surface transport of the hemagglutinin-neuraminidase (HN) protein co-expressed with each of these cysteine mutant F proteins was also reduced. These results suggest that all cysteine residues participate in the formation of intramolecular disulfide bonds, that co-translational disulfide bond formation is crucial to the correct folding and intracellular transport of the F protein, and that interaction of the F and HN proteins takes place intracellulary. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109880/ doi: 10.1093/oxfordjournals.jbchem.a022044 id: cord-002973-bkr4ndl2 author: Seifi, Morteza title: Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms date: 2018-04-17 words: 5062.0 sentences: 237.0 pages: flesch: 40.0 cache: ./cache/cord-002973-bkr4ndl2.txt txt: ./txt/cord-002973-bkr4ndl2.txt summary: Our results showed that for PITX2, and likely other members of this homeodomain transcription factor family, MutPred, Provean, PMUT, molecular modeling, and CUPSAT can reliably be used to predict PITX2 missense variants pathogenicity. The protein sequence and/or protein structure with mutational position and amino acid residue of 18 previously functionally characterized pathogenic PITX2 missense variants, plus 16 SNPs with a population frequency of higher than 0.05% (thus considered benign polymorphisms), were used to test the predictive value of eleven common bioinformatics prediction programs; SIFT, PolyPhen-2, PANTHER-PSEP, MutPred, MutationTaster, Provean, PMUT, FATHMM, nsSNPAnalyzer, Align GV-GD, and REVEL (Table 4 and Table 5 ). To assess the performance of eight different stability predictor programs (DUET, SDM, mCSM, I-Mutant3.0, MUpro, iPTREE-STAB, CUPSAT, and iStable) in predicting the effect of missense mutations on PITX2 protein stability, the change in protein stability (ΔΔG) were computed for all 24 PITX2 homeodomain variants (15 functionally characterised and 9 functionally uncharacterised mutations) (Table 7) . abstract: Mutations in PITX2 have been implicated in several genetic disorders, particularly Axenfeld-Rieger syndrome. In order to determine the most reliable bioinformatics tools to assess the likely pathogenicity of PITX2 variants, the results of bioinformatics predictions were compared to the impact of variants on PITX2 structure and function. The MutPred, Provean, and PMUT bioinformatic tools were found to have the highest performance in predicting the pathogenicity effects of all 18 characterized missense variants in PITX2, all with sensitivity and specificity >93%. Applying these three programs to assess the likely pathogenicity of 13 previously uncharacterized PITX2 missense variants predicted 12/13 variants as deleterious, except A30V which was predicted as benign variant for all programs. Molecular modeling of the PITX2 homoedomain predicts that of the 31 known PITX2 variants, L54Q, F58L, V83F, V83L, W86C, W86S, and R91P alter PITX2’s structure. In contrast, the remaining 24 variants are not predicted to change PITX2’s structure. The results of molecular modeling, performed on all the PITX2 missense mutations located in the homeodomain, were compared with the findings of eight protein stability programs. CUPSAT was found to be the most reliable in predicting the effect of missense mutations on PITX2 stability. Our results showed that for PITX2, and likely other members of this homeodomain transcription factor family, MutPred, Provean, PMUT, molecular modeling, and CUPSAT can reliably be used to predict PITX2 missense variants pathogenicity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903617/ doi: 10.1371/journal.pone.0195971 id: cord-292958-k5d5fo3i author: Sekhon, Simranjeet Singh title: Porcine epidemic diarrhea (PED) infection, diagnosis and vaccination: A mini review date: 2017-01-04 words: 7430.0 sentences: 299.0 pages: flesch: 41.0 cache: ./cache/cord-292958-k5d5fo3i.txt txt: ./txt/cord-292958-k5d5fo3i.txt summary: Porcine epidemic diarrhea virus (PEDV) is a main etiology causing severe enteric disease in piglets with clinical signs of anorexia, vomiting, diarrhea and dehydration resulting in loss of condition and death within a few days. Many techniques are available for the detection of PEDV from fecal materials, small infected intestines sample, including reverse transcript polymerase chain reaction (RT-PCR), direct immunofluorescence tests (IF), indirect fluorescence antibody tests (IFA), immunohistochemistry techniques (IHC), in situ hydridization, electron microscopy and enzyme-linked immunosorbent assays (ELISA) 2 . (2012) used the Vero cell cultures to isolate CHGD-01 PEDV strain as well as employed direct immunofluorescence assay and EM technique to investigate its specific cytopathic effects in the outbreak of diarrhea in Guangdong (South China) swine 18 . The RT-PCR system in this study could effectively detect PEDV RNA from viral mixtures or small intestinal/ fecal samples in very low number of virus within short time. abstract: Porcine epidemic diarrhea virus (PEDV) is a main etiology causing severe enteric disease in piglets with clinical signs of anorexia, vomiting, diarrhea and dehydration resulting in loss of condition and death within a few days. Historically, PED is one of major causes of loss in swine and remains prevalent in some parts of the world. Even with increase in the available tests for PED diagnosis, which include histological diagnosis; virological diagnosis and serological diagnosis, there is no vaccine or specific treatment for this disease yet. In this mini review, the overview and current situation of PED is described with updated techniques, in an effort to comprehensively discuss and understand the disease characteristics. url: https://www.ncbi.nlm.nih.gov/pubmed/32226596/ doi: 10.1007/s13530-016-0287-8 id: cord-342634-4ouhdjsr author: Semrad, Katharina title: Proteins with RNA Chaperone Activity: A World of Diverse Proteins with a Common Task—Impediment of RNA Misfolding date: 2010-12-26 words: 7141.0 sentences: 399.0 pages: flesch: 52.0 cache: ./cache/cord-342634-4ouhdjsr.txt txt: ./txt/cord-342634-4ouhdjsr.txt summary: In brief, the group of proteins with RNA chaperone activity includes proteins that, first, open up misfolded structures without requirement of ATP and that, second, are dispensable once the RNA has been folded. coli showed that 1/3 of the tested proteins possesses strong RNA chaperone activity in vitro in the trans-splicing assay [21] . E. coli contains nine members of the csp family and CspA, the major cold-shock protein and CspE were identified to interact non-specifically with RNA molecules and to possess nucleic acid melting activities [44] [45] [46] . Later, a detailed study on possible functions of Ro RNPs, which are Ro ribonucleoprotein complexes, composed of a small noncoding cytoplasmic RNA, termed Y RNA and its protein partners was conducted: besides the permanently associated proteins Ro60 and La, subpopulations of Ro-RNPs also contain hnRNP I and hnRNP K, both of which exhibited strong RNA chaperone activity in vitro in the transsplicing and the cis-splicing assay [22] . abstract: Proteins with RNA chaperone activity are ubiquitous proteins that play important roles in cellular mechanisms. They prevent RNA from misfolding by loosening misfolded structures without ATP consumption. RNA chaperone activity is studied in vitro and in vivo using oligonucleotide- or ribozyme-based assays. Due to their functional as well as structural diversity, a common chaperoning mechanism or universal motif has not yet been identified. A growing database of proteins with RNA chaperone activity has been established based on evaluation of chaperone activity via the described assays. Although the exact mechanism is not yet understood, it is more and more believed that disordered regions within proteins play an important role. This possible mechanism and which proteins were found to possess RNA chaperone activity are discussed here. url: https://www.ncbi.nlm.nih.gov/pubmed/21234377/ doi: 10.1155/2011/532908 id: cord-342756-rgm9ffpk author: Senger, Mario Roberto title: COVID-19: molecular targets, drug repurposing and new avenues for drug discovery date: 2020-10-02 words: 16108.0 sentences: 1024.0 pages: flesch: 51.0 cache: ./cache/cord-342756-rgm9ffpk.txt txt: ./txt/cord-342756-rgm9ffpk.txt summary: Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. In the following topic, we will review SARS-CoV-2 structure and mechanism of infection in order to discuss molecular targets from the virus or its human host that are being considered for drug repurposing and perhaps future development of new drugs. (128) Its role as a functional receptor of SARS-CoV-2 S protein in host cells makes this protein a potential drug target to treat COVID-19. (138) TMPRSS2 has a major role in SARS-CoV-2 cell entry and replication, and thus represents an interesting therapeutic target since its inhibitors could potentially block virus infection in its initial stages. (199) A robust preclinical drug discovery pipeline comprising in vitro, and in vivo models of SARS-CoV-2 infection is particularly important to identify new antivirals for human COVID-19 treatment. abstract: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment. url: https://www.ncbi.nlm.nih.gov/pubmed/33027420/ doi: 10.1590/0074-02760200254 id: cord-350558-qfdp4ov9 author: Shaban, Mohammed Samer title: Inhibiting coronavirus replication in cultured cells by chemical ER stress date: 2020-08-26 words: 5077.0 sentences: 297.0 pages: flesch: 58.0 cache: ./cache/cord-350558-qfdp4ov9.txt txt: ./txt/cord-350558-qfdp4ov9.txt summary: We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. A detailed proteomics analysis reveals multiple thapsigargin-78 regulated pathways and a network of proteins that are suppressed by CoV but (re)activated by 79 chemically stressed infected cells. we determined the expression levels of 166 components of the ER stress pathway KEGG 04141 85 "protein processing in endoplasmic reticulum" in human HuH7 liver cells, a commonly used cellular 86 model for CoV replication, in response to infections with HCoV-229E and MERS-CoV, respectively. The highly inducible HERPUD1 protein has an essential scaffolding function for the organization of searching our proteomics data for further ERAD factors we were able to retrieve a total of 34 (for 284 MERS-CoV) and 20 (for SARS-CoV-2) proteins of the canonical ERQC and ERAD pathways for 285 which a differential expression was observed in virus-infected cells treated with thapsigargin (Fig. 286 5H) . abstract: Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. Proteome-wide data sets revealed specific pathways, protein networks and components that likely mediate the thapsigargin-induced antiviral state, including HERPUD1, an essential factor of ER quality control, and ER-associated protein degradation complexes. The data show that thapsigargin hits a central mechanism required for CoV replication, suggesting that thapsigargin (or derivatives thereof) may be developed into broad-spectrum anti-CoV drugs. One Sentence Summary / Running title Suppression of coronavirus replication through thapsigargin-regulated ER stress, ERQC / ERAD and metabolic pathways url: https://doi.org/10.1101/2020.08.26.266304 doi: 10.1101/2020.08.26.266304 id: cord-322926-xlwsj3v2 author: Shanmugaraj, Balamurugan title: Plant Molecular Farming: A Viable Platform for Recombinant Biopharmaceutical Production date: 2020-07-04 words: 4666.0 sentences: 228.0 pages: flesch: 31.0 cache: ./cache/cord-322926-xlwsj3v2.txt txt: ./txt/cord-322926-xlwsj3v2.txt summary: Given the speed advantages, and proven viability of the plant production platform, the transient expression system in particular could be employed to produce recombinant proteins at high levels to meet the sudden demand for production of viral antigens or antiviral proteins that could be used as research reagents, emergency vaccines (SARS-CoV-2 subunit and virus-like particle vaccines), or other biopharmaceuticals to fight against COVID-19 [25, 124] . Given the speed advantages, and proven viability of the plant production platform, the transient expression system in particular could be employed to produce recombinant proteins at high levels to meet the sudden demand for production of viral antigens or antiviral proteins that could be used as research reagents, emergency vaccines (SARS-CoV-2 subunit and virus-like particle vaccines), or other biopharmaceuticals to fight against COVID-19 [25, 124] . abstract: The demand for recombinant proteins in terms of quality, quantity, and diversity is increasing steadily, which is attracting global attention for the development of new recombinant protein production technologies and the engineering of conventional established expression systems based on bacteria or mammalian cell cultures. Since the advancements of plant genetic engineering in the 1980s, plants have been used for the production of economically valuable, biologically active non-native proteins or biopharmaceuticals, the concept termed as plant molecular farming (PMF). PMF is considered as a cost-effective technology that has grown and advanced tremendously over the past two decades. The development and improvement of the transient expression system has significantly reduced the protein production timeline and greatly improved the protein yield in plants. The major factors that drive the plant-based platform towards potential competitors for the conventional expression system are cost-effectiveness, scalability, flexibility, versatility, and robustness of the system. Many biopharmaceuticals including recombinant vaccine antigens, monoclonal antibodies, and other commercially viable proteins are produced in plants, some of which are in the pre-clinical and clinical pipeline. In this review, we consider the importance of a plant- based production system for recombinant protein production, and its potential to produce biopharmaceuticals is discussed. url: https://www.ncbi.nlm.nih.gov/pubmed/32635427/ doi: 10.3390/plants9070842 id: cord-290472-w77cmljm author: Sharon, Donald title: Systems Biology Approaches to Disease Marker Discovery date: 2010-06-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Our understanding of human disease and potential therapeutics is improving rapidly. In order to take advantage of these developments it is important to be able to identify disease markers. Many new high-throughput genomics and proteomics technologies are being implemented to identify candidate disease markers. These technologies include protein microarrays, next-generation DNA sequencing and mass spectrometry platforms. Such methods are particularly important for elucidating the repertoire of molecular markers in the genome, transcriptome, proteome and metabolome of patients with diseases such as cancer, autoimmune diseases, and viral infections, resulting from the disruption of many biological pathways. These new technologies have identified many potential disease markers. These markers are expected to be valuable to achieve the promise of truly personalized medicine. url: https://www.ncbi.nlm.nih.gov/pubmed/20534906/ doi: 10.3233/dma-2010-0707 id: cord-008293-5cwb5g3h author: Shaw, Shyh-Yu title: Analogous amino acid sequences in myelin proteolipid and viral proteins date: 1986-10-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Computer analysis of the intrinsic membrane protein, myelin proteolipid, shows strong sequence similarities between the putative extramembrane segments of the proteolipid protein and a number of viral proteins, several of which infect humans. These similarities are even more striking than those reported previously between viral proteins and the encephalitogenic myelin basic protein (MBP). These findings, along with other reports of molecular mimicry by viruses, suggest that immunological cross‐reactions between virus‐induced antibodies or T‐cells and analogous antigenic determinants (epitopes) in myelin proteolipid could be involved in the pathophysiology of multiple sclerosis or post‐infectious demyelinating syndromes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7130213/ doi: 10.1016/0014-5793(86)81502-2 id: cord-000884-zq8kqf6h author: Shen, Hsin-Hui title: Reconstitution of Membrane Proteins into Model Membranes: Seeking Better Ways to Retain Protein Activities date: 2013-01-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The function of any given biological membrane is determined largely by the specific set of integral membrane proteins embedded in it, and the peripheral membrane proteins attached to the membrane surface. The activity of these proteins, in turn, can be modulated by the phospholipid composition of the membrane. The reconstitution of membrane proteins into a model membrane allows investigation of individual features and activities of a given cell membrane component. However, the activity of membrane proteins is often difficult to sustain following reconstitution, since the composition of the model phospholipid bilayer differs from that of the native cell membrane. This review will discuss the reconstitution of membrane protein activities in four different types of model membrane—monolayers, supported lipid bilayers, liposomes and nanodiscs, comparing their advantages in membrane protein reconstitution. Variation in the surrounding model environments for these four different types of membrane layer can affect the three-dimensional structure of reconstituted proteins and may possibly lead to loss of the proteins activity. We also discuss examples where the same membrane proteins have been successfully reconstituted into two or more model membrane systems with comparison of the observed activity in each system. Understanding of the behavioral changes for proteins in model membrane systems after membrane reconstitution is often a prerequisite to protein research. It is essential to find better solutions for retaining membrane protein activities for measurement and characterization in vitro. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565336/ doi: 10.3390/ijms14011589 id: cord-345088-krb1eidw author: Shen, S title: A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature date: 2004-09-01 words: 6949.0 sentences: 316.0 pages: flesch: 56.0 cache: ./cache/cord-345088-krb1eidw.txt txt: ./txt/cord-345088-krb1eidw.txt summary: title: A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature Here, we report the emergence and isolation of two temperature sensitive (ts) mutants and a revertant in the process of cold-adaptation of coronavirus infectious bronchitis virus (IBV) to a monkey kidney cell line. Evidence presented demonstrated that the Q(294)-to-L(294) mutation, located at a highly conserved domain of the S1 subunit, might hamper processing of the S protein to a matured 180-kDa, endo-glycosidase H-resistant glycoprotein and the translocation of the protein to the cell surface. In virus-infected cells, the Endo-H sensitive, 155-kDa form of ts291602 was abundant at the nonpermissive temperature, clearly indicating that the mutant S protein was trimmed in the ER and cis-Golgi but was not transported to the trans-Golgi. abstract: The spike (S) glycoprotein of coronavirus is responsible for receptor binding and membrane fusion. A number of variants with deletions and mutations in the S protein have been isolated from naturally and persistently infected animals and tissue cultures. Here, we report the emergence and isolation of two temperature sensitive (ts) mutants and a revertant in the process of cold-adaptation of coronavirus infectious bronchitis virus (IBV) to a monkey kidney cell line. The complete sequences of wild type (wt) virus, two ts mutants, and the revertant were compared and variations linked to phenotypes were mapped. A single amino acid reversion (L(294)-to-Q) in the S protein is sufficient to abrogate the ts phenotype. Interestingly, unlike wt virus, the revertant grows well at and below 32 °C, the permissive temperature, as it carries other mutations in multiple genes that might be associated with the cold-adaptation phenotype. If the two ts mutants were allowed to enter cells at 32 °C, the S protein was synthesized, core-glycosylated and at least partially modified at 40 °C. However, compared with wt virus and the revertant, no infectious particles of these ts mutants were assembled and released from the ts mutant-infected cells at 40 °C. Evidence presented demonstrated that the Q(294)-to-L(294) mutation, located at a highly conserved domain of the S1 subunit, might hamper processing of the S protein to a matured 180-kDa, endo-glycosidase H-resistant glycoprotein and the translocation of the protein to the cell surface. Consequently, some essential functions of the S protein, including mediation of cell-to-cell fusion and its incorporation into virions, were completely abolished. url: https://api.elsevier.com/content/article/pii/S0042682204003988 doi: 10.1016/j.virol.2004.06.016 id: cord-003070-6oca1mrm author: Shen, Wen-Jun title: RPiRLS: Quantitative Predictions of RNA Interacting with Any Protein of Known Sequence date: 2018-02-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: RNA-protein interactions (RPIs) have critical roles in numerous fundamental biological processes, such as post-transcriptional gene regulation, viral assembly, cellular defence and protein synthesis. As the number of available RNA-protein binding experimental data has increased rapidly due to high-throughput sequencing methods, it is now possible to measure and understand RNA-protein interactions by computational methods. In this study, we integrate a sequence-based derived kernel with regularized least squares to perform prediction. The derived kernel exploits the contextual information around an amino acid or a nucleic acid as well as the repetitive conserved motif information. We propose a novel machine learning method, called RPiRLS to predict the interaction between any RNA and protein of known sequences. For the RPiRLS classifier, each protein sequence comprises up to 20 diverse amino acids but for the RPiRLS-7G classifier, each protein sequence is represented by using 7-letter reduced alphabets based on their physiochemical properties. We evaluated both methods on a number of benchmark data sets and compared their performances with two newly developed and state-of-the-art methods, RPI-Pred and IPMiner. On the non-redundant benchmark test sets extracted from the PRIDB, the RPiRLS method outperformed RPI-Pred and IPMiner in terms of accuracy, specificity and sensitivity. Further, RPiRLS achieved an accuracy of 92% on the prediction of lncRNA-protein interactions. The proposed method can also be extended to construct RNA-protein interaction networks. The RPiRLS web server is freely available at http://bmc.med.stu.edu.cn/RPiRLS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017498/ doi: 10.3390/molecules23030540 id: cord-330475-mameyzih author: Shi, Da title: Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus date: 2014-03-13 words: 5570.0 sentences: 296.0 pages: flesch: 44.0 cache: ./cache/cord-330475-mameyzih.txt txt: ./txt/cord-330475-mameyzih.txt summary: Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. The B23.1-DsRed fusion protein was used to tag the nucleolus, so we could analyze nucleolar localization properties and colocalization in cotransfected cells by live cell imaging (direct fluorescence) or confocal microscopy. These expression plasmids were transfected into Vero E6 cells, the nuclear was stained with DAPI at 24 h post-transfection indicated that amino acids 148-220 directed AcGFP to the cytoplasm and nucleus and had a subcellular localization similar to AcGFP. abstract: The nucleolus is a dynamic subnuclear structure, which is crucial to the normal operation of the eukaryotic cell. The porcine epidemic diarrhea virus (PEDV), coronavirus nucleocapsid (N) protein, plays important roles in the process of virus replication and cellular infection. Virus infection and transfection showed that N protein was predominately localized in the cytoplasm, but also found in the nucleolus in Vero E6 cells. Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. We also identified two nuclear export signals (NES, aa221–236, and 325–364), however, only the nuclear export signal (aa325–364) was found to be functional in the context of the full-length N protein. Finally, the activity of this nuclear export signal (NES) was inhibited by the antibiotic Lepomycin B, suggesting that N is exported by a chromosome region maintenance 1-related export pathway. url: https://www.ncbi.nlm.nih.gov/pubmed/24632575/ doi: 10.3390/v6031253 id: cord-354050-kcn67stj author: Shi, Guoli title: More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins date: 2017-11-21 words: 6846.0 sentences: 313.0 pages: flesch: 36.0 cache: ./cache/cord-354050-kcn67stj.txt txt: ./txt/cord-354050-kcn67stj.txt summary: Most of what we know about the antiviral activities of IFITM proteins results from work using IAV and vesicular stomatitis virus (VSV), which perform pH-dependent fusion reactions in endosomes to gain access to the cell interior [22] . As the primary determinant for virus-cell attachment and the subsequent fusion reaction, the viral envelope glycoprotein (Env) was suspected to play an important role in whether or not HIV-1 and related lentiviruses are subject to inhibition by IFITM proteins. In addition to restricting virus entry, recent findings indicate that IFITM proteins perform antiviral functions impacting late stages of the HIV-1 life cycle. This antiviral activity is enhanced upon expression of an IFITM3 mutant that is defective for endocytosis, indicating that restriction of HIV-1 virion infectivity is performed at the plasma membrane [5] . Nonetheless, the recent identification of Env variants that are resistant to the IFITM3-mediated restriction of virion infectivity confirms this viral protein as an important determinant. abstract: The first responders of human antiviral immunity are components of the intrinsic immune response that reside within each and every one of our cells. This cell-autonomous arsenal consists of nucleic acid sensors and antiviral effectors strategically placed by evolution to detect and restrict invading viruses. While some factors are present at baseline to allow for constant surveillance of the cell interior, others are upregulated by cytokines (such as interferons) that signal a viral infection underway in neighboring cells. In this review, we highlight the multiple roles played by the interferon-induced transmembrane (IFITM) proteins during viral infection, with focuses on IFITM3 and HIV-1. Moreover, we discuss the cellular pathways in which IFITM proteins are intertwined and the various functions they have been ascribed outside the context of infection. While appreciated as broadly-acting, potent restriction factors that prevent virus infection and pathogenesis in cell culture and in vivo, questions remain regarding their precise mode of action and importance in certain viral contexts. Continued efforts to study IFITM protein function will further cement their status as critical host determinants of virus susceptibility and prioritize them in the development of new antiviral therapies. url: https://doi.org/10.1186/s12977-017-0377-y doi: 10.1186/s12977-017-0377-y id: cord-281101-gv1sgbk1 author: Shin, Gu-Choul title: Preparation and characterization of a novel monoclonal antibody specific to severe acute respiratory syndrome-coronavirus nucleocapsid protein date: 2006-08-30 words: 5929.0 sentences: 279.0 pages: flesch: 52.0 cache: ./cache/cord-281101-gv1sgbk1.txt txt: ./txt/cord-281101-gv1sgbk1.txt summary: Severe acute respiratory syndrome-coronavirus nucleocapsid (SARS-CoV N) protein has been found to be important to the processes related to viral pathogenesis, such as virus replication, interference of the cell process and modulation of host immune response; detection of the antigen has been used for the early diagnosis of infection. Reactivity of SARS-N mAbs with SARS-CoV infected cells was determined by immunofluorescence assay, performed according to the instructions of the manufacturer (Euroimmun, Germany). To further assess the specificity of the mAbs, antigen-capture ELISA was performed with human coronavirus-infected cell lysates and BrSARS-N protein as positive control (Fig. 6B) . (B) Cross-reactivity of SARS-N mAbs was examined by antigen-capture ELISA using human coronavirus OC43 lysates (256 HA unit), BrSARS-N protein (500 ng/well) and PBST buffer with 1% BSA as control. These mAbs were available for use in detecting SARS-CoV N protein by various diagnostic methods, such as immunoblot assay, immunofluorescence assay and antigen-capture ELISA (Table 3) . abstract: Severe acute respiratory syndrome-coronavirus nucleocapsid (SARS-CoV N) protein has been found to be important to the processes related to viral pathogenesis, such as virus replication, interference of the cell process and modulation of host immune response; detection of the antigen has been used for the early diagnosis of infection. We have used recombinant N protein expressed in insect cells to generate 17 mAbs directed against this protein. We selected five mAbs that could be used in various diagnostic assays, and all of these mAbs recognized linear epitopes. Three IgG(2b) mAbs were recognized within the N-terminus of N protein, whereas the epitope of two IgG(1) mAbs localized within the C-terminus. These mAbs were found to have significant reactivity with both non-phosphorylated and phosphorylated N proteins, which resulted in high reactivity with native N protein in virus-infected cells; however, they did not show cross-reactivity with human coronavirus. Therefore, these results suggested that these mAbs would be useful in the development of various diagnostic kits and in future studies of SARS-CoV pathology. url: https://www.ncbi.nlm.nih.gov/pubmed/16942813/ doi: 10.1016/j.virusres.2006.07.004 id: cord-009636-5kddituy author: Shirbaghaee, Zeinab title: Different applications of virus‐like particles in biology and medicine: Vaccination and delivery systems date: 2015-12-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Virus‐like particles (VLPs) mimic the whole construct of virus particles devoid of viral genome as used in subunit vaccine design. VLPs can elicit efficient protective immunity as direct immunogens compared to soluble antigens co‐administered with adjuvants in several booster injections. Up to now, several prokaryotic and eukaryotic systems such as insect, yeast, plant, and E. coli were used to express recombinant proteins, especially for VLP production. Recent studies are also generating VLPs in plants using different transient expression vectors for edible vaccines. VLPs and viral particles have been applied for different functions such as gene therapy, vaccination, nanotechnology, and diagnostics. Herein, we describe VLP production in different systems as well as its applications in biology and medicine. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 113–132, 2016. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161881/ doi: 10.1002/bip.22759 id: cord-287477-aios0h8s author: Sicari, Daria title: Role of the early secretory pathway in SARS-CoV-2 infection date: 2020-07-28 words: 6483.0 sentences: 359.0 pages: flesch: 44.0 cache: ./cache/cord-287477-aios0h8s.txt txt: ./txt/cord-287477-aios0h8s.txt summary: CoV-2 infection starts when its spike (S) protein binds to angiotensin I-converting enzyme 2 (ACE2) receptors on the host cell membrane (Lake, 2020; Letko et al., 2020) . Thus, virion spread critically depends on recruiting the most efficient secretory machineries of host cells (Su et al., 2016; Proteins of the early secretory pathway bound by SARS-CoV-2 As the entire world asks for ways to stop CoV-2, many laboratories are investigating the virus''s Achilles heel(s). The role of glycosylation and protein quality control in SARS-CoV-2 infections Most CoVs bud at the ERGIC level ( Fig. 1) and are then transported along the exocytic pathway (Klumperman et al., 1994; Stertz et al., 2007) . We observed enrichment for five host-derived virus-interacting proteins (GOLGB1, PDE4DIP, TOR1A, HMOX1, and HYOU1) involved in different processes and related to quality control and ER-Golgi homeostasis maintenance. abstract: Similar to other RNA viruses, SARS-CoV-2 must (1) enter a target/host cell, (2) reprogram it to ensure its replication, (3) exit the host cell, and (4) repeat this cycle for exponential growth. During the exit step, the virus hijacks the sophisticated machineries that host cells employ to correctly fold, assemble, and transport proteins along the exocytic pathway. Therefore, secretory pathway–mediated assemblage and excretion of infective particles represent appealing targets to reduce the efficacy of virus biogenesis, if not to block it completely. Here, we analyze and discuss the contribution of the molecular machines operating in the early secretory pathway in the biogenesis of SARS-CoV-2 and their relevance for potential antiviral targeting. The fact that these molecular machines are conserved throughout evolution, together with the redundancy and tissue specificity of their components, provides opportunities in the search for unique proteins essential for SARS-CoV-2 biology that could also be targeted with therapeutic objectives. Finally, we provide an overview of recent evidence implicating proteins of the early secretory pathway as potential antiviral targets with effective therapeutic applications. url: https://doi.org/10.1083/jcb.202006005 doi: 10.1083/jcb.202006005 id: cord-290290-wyx9ib7s author: Sinegubova, Maria V. title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date: 2020-11-05 words: 5978.0 sentences: 304.0 pages: flesch: 49.0 cache: ./cache/cord-290290-wyx9ib7s.txt txt: ./txt/cord-290290-wyx9ib7s.txt summary: title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. Previously we have developed the plasmid vector p1.1, containing large fragments of non-coding DNA from the EEF1A1 gene of the Chinese hamster and fragment of the Epstein-Barr virus long terminal repeat concatemer [21] and employed it for unusually high-level expression of various proteins in CHO cells, including blood clotting factors VIII [22] , IX [23] , and heterodimeric follicle-stimulating hormone [24] . We have proposed that SARS-CoV-2 RBD, suitable for in vitro diagnostics use, may be expressed in large quantities by stably transfected CHO cells, bearing the EEF1A1-based plasmid. abstract: The spike (S) protein is one of the three proteins forming the coronaviruses’ viral envelope. The S protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has a spatial structure similar to the S proteins of other mammalian coronaviruses, except for a unique receptor-binding domain (RBD), which is a significant inducer of host immune response. Recombinant SARS-CoV-2 RBD is widely used as a highly specific minimal antigen for serological tests. Correct exposure of antigenic determinants has a significant impact on the accuracy of such tests – the antigen has to be correctly folded, contain no potentially antigenic non-vertebrate glycans, and, preferably, should have a glycosylation pattern similar to the native S protein. Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. RBDv1 contained a native viral signal peptide, RBDv2 – human tPA signal peptide. We transfected a CHO DG44 cell line, selected stably transfected cells, and performed a few rounds of methotrexate-driven amplification of the genetic cassette in the genome. For the RBDv2 variant, a high-yield clonal producer cell line was obtained. We developed a simple purification scheme that consistently yielded up to 30 mg of RBD protein per liter of the simple shake flask cell culture. Purified proteins were analyzed by polyacrylamide gel electrophoresis in reducing and non-reducing conditions and gel filtration; for RBDv2 protein, the monomeric form content exceeded 90% for several series. Deglycosylation with PNGase F and mass spectrometry confirmed the presence of N-glycosylation. The antigen produced by the described technique is suitable for serological tests and similar applications. url: https://doi.org/10.1101/2020.11.04.368092 doi: 10.1101/2020.11.04.368092 id: cord-281005-6gi18vka author: Singh, Praveen Kumar title: Mutations in SARS-CoV-2 Leading to Antigenic Variations in Spike Protein: A Challenge in Vaccine Development date: 2020-09-01 words: 3161.0 sentences: 203.0 pages: flesch: 57.0 cache: ./cache/cord-281005-6gi18vka.txt txt: ./txt/cord-281005-6gi18vka.txt summary: title: Mutations in SARS-CoV-2 Leading to Antigenic Variations in Spike Protein: A Challenge in Vaccine Development Therefore, we aimed to predict the mutations in the spike protein (S) of the SARS-CoV-2 genomes available worldwide and analyze its impact on the antigenicity. A total of 1,604 spike proteins were extracted from 1,325 complete genome and 279 partial spike coding sequences of SARS-CoV-2 available in NCBI till May 1, 2020 and subjected to multiple sequence alignment to find the mutations corresponding to the reported single nucleotide polymorphisms (SNPs) in the genomic study. In this study, we aimed to predict the mutations in the spike protein (S) of SARS-CoV-2 genomes available in the database (whole genome sequences as well as partial coding sequences of spike protein) and analyze the effect of each mutation on the antigenicity of the predicted epitopes. abstract: Objectives The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has been unprecedentedly fast, spreading to more than 180 countries within 3 months with variable severity. One of the major reasons attributed to this variation is genetic mutation. Therefore, we aimed to predict the mutations in the spike protein (S) of the SARS-CoV-2 genomes available worldwide and analyze its impact on the antigenicity. Materials and Methods Several research groups have generated whole genome sequencing data which are available in the public repositories. A total of 1,604 spike proteins were extracted from 1,325 complete genome and 279 partial spike coding sequences of SARS-CoV-2 available in NCBI till May 1, 2020 and subjected to multiple sequence alignment to find the mutations corresponding to the reported single nucleotide polymorphisms (SNPs) in the genomic study. Further, the antigenicity of the predicted mutations inferred, and the epitopes were superimposed on the structure of the spike protein. Results The sequence analysis resulted in high SNPs frequency. The significant variations in the predicted epitopes showing high antigenicity were A348V, V367F and A419S in receptor binding domain (RBD). Other mutations observed within RBD exhibiting low antigenicity were T323I, A344S, R408I, G476S, V483A, H519Q, A520S, A522S and K529E. The RBD T323I, A344S, V367F, A419S, A522S and K529E are novel mutations reported first time in this study. Moreover, A930V and D936Y mutations were observed in the heptad repeat domain and one mutation D1168H was noted in heptad repeat domain 2. Conclusion S protein is the major target for vaccine development, but several mutations were predicted in the antigenic epitopes of S protein across all genomes available globally. The emergence of various mutations within a short period might result in the conformational changes of the protein structure, which suggests that developing a universal vaccine may be a challenging task. url: https://doi.org/10.1055/s-0040-1715790 doi: 10.1055/s-0040-1715790 id: cord-260225-bc1hr0fr author: Sirpilla, Olivia title: SARS-CoV-2-Encoded Proteome and Human Genetics: From Interaction-Based to Ribosomal Biology Impact on Disease and Risk Processes date: 2020-07-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: [Image: see text] SARS-CoV-2 (COVID-19) has infected millions of people worldwide, with lethality in hundreds of thousands. The rapid publication of information, both regarding the clinical course and the viral biology, has yielded incredible knowledge of the virus. In this review, we address the insights gained for the SARS-CoV-2 proteome, which we have integrated into the Viral Integrated Structural Evolution Dynamic Database, a publicly available resource. Integrating evolutionary, structural, and interaction data with human proteins, we present how the SARS-CoV-2 proteome interacts with human disorders and risk factors ranging from cytokine storm, hyperferritinemic septic, coagulopathic, cardiac, immune, and rare disease-based genetics. The most noteworthy human genetic potential of SARS-CoV-2 is that of the nucleocapsid protein, where it is known to contribute to the inhibition of the biological process known as nonsense-mediated decay. This inhibition has the potential to not only regulate about 10% of all biological transcripts through altered ribosomal biology but also associate with viral-induced genetics, where suppressed human variants are activated to drive dominant, negative outcomes within cells. As we understand more of the dynamic and complex biological pathways that the proteome of SARS-CoV-2 utilizes for entry into cells, for replication, and for release from human cells, we can understand more risk factors for severe/lethal outcomes in patients and novel pharmaceutical interventions that may mitigate future pandemics. url: https://doi.org/10.1021/acs.jproteome.0c00421 doi: 10.1021/acs.jproteome.0c00421 id: cord-298369-66ifwtlp author: Smith, Sherri A. title: Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein date: 2018-12-28 words: 10621.0 sentences: 491.0 pages: flesch: 46.0 cache: ./cache/cord-298369-66ifwtlp.txt txt: ./txt/cord-298369-66ifwtlp.txt summary: The importance of plasma protein binding primarily resides in its impact on pharmacokinetic properties such as clearance (CL) and volume of distribution (V ss ), with serum albumin, lipoproteins and alpha-1 acid glycoprotein (AAG) being the major proteins involved in sequestering drugs in plasma (1) . While AAG represents a relatively small portion (~1-3%) of the total plasma proteins, compared to~60% composition of albumin, it can play a significant role in drug binding and pharmacokinetics (PK) (43) . Since AAG levels increase in most disease states (46) , drugs with a high affinity may demonstrate higher binding (lower fraction unbound, f u ) and altered PK properties (e.g. lower total CL), lower V ss . Effect of the plasticizer DEHP in blood collection bags on human plasma fraction unbound determination for Alpha-1-Acid Glycoprotein (AAG) binding drugs abstract: According to the free drug hypothesis only the unbound drug is available to act at physiological sites of action, and as such the importance of plasma protein binding primarily resides in its impact on pharmacokinetics and pharmacodynamics. Of the major plasma proteins, alpha-1-acid glycoprotein (AAG) represents an intriguing one primarily due to the high affinity, low capacity properties of this protein. In addition, there are marked species and age differences in protein expression, homology and drug binding affinity. As such, a thorough understanding of drug binding to AAG can help aid and improve the translation of pharmacokinetic/pharmacodynamic (PK/PD) relationships from preclinical species to human as well as adults to neonates. This review provides a comprehensive overview of our current understanding of the biochemistry of AAG; endogenous function, impact of disease, utility as a biomarker, and impact on PK/PD. Experimental considerations are discussed as well as recommendations for understanding the potential impact of AAG on PK through drug discovery and early development. url: https://www.ncbi.nlm.nih.gov/pubmed/30593605/ doi: 10.1007/s11095-018-2551-x id: cord-259603-bh198xgl author: Snijder, E.J. title: The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing date: 2016-09-14 words: 24187.0 sentences: 1090.0 pages: flesch: 50.0 cache: ./cache/cord-259603-bh198xgl.txt txt: ./txt/cord-259603-bh198xgl.txt summary: Reverse-genetics studies targeting specific residues in SARS-CoV nsp7 confirmed the protein''s importance for virus replication (Subissi et al., 2014b) , although the impact of single point mutations was smaller than anticipated on the basis of the biochemical characterization of the RNA-binding properties of nsp7-containing protein complexes in vitro (see later). The large number of viral subunits in these complexes (Subissi et al., 2014a) , the likely requirement for host factors (van Hemert et al., 2008) , and the concept of RNA synthesis occurring in a dedicated microenvironment in the infected cell (Knoops et al., 2008; V''Kovski et al., 2015) complicate the straightforward characterization of the CoV RdRp. To reconstitute the enzyme''s activities in vitro, purified recombinant nsp12 is a key reagent but, for many years, such studies were hampered by poor nsp12 expression in Escherichia coli. abstract: Coronaviruses are animal and human pathogens that can cause lethal zoonotic infections like SARS and MERS. They have polycistronic plus-stranded RNA genomes and belong to the order Nidovirales, a diverse group of viruses for which common ancestry was inferred from the common principles underlying their genome organization and expression, and from the conservation of an array of core replicase domains, including key RNA-synthesizing enzymes. Coronavirus genomes (~ 26–32 kilobases) are the largest RNA genomes known to date and their expansion was likely enabled by acquiring enzyme functions that counter the commonly high error frequency of viral RNA polymerases. The primary functions that direct coronavirus RNA synthesis and processing reside in nonstructural protein (nsp) 7 to nsp16, which are cleavage products of two large replicase polyproteins translated from the coronavirus genome. Significant progress has now been made regarding their structural and functional characterization, stimulated by technical advances like improved methods for bioinformatics and structural biology, in vitro enzyme characterization, and site-directed mutagenesis of coronavirus genomes. Coronavirus replicase functions include more or less universal activities of plus-stranded RNA viruses, like an RNA polymerase (nsp12) and helicase (nsp13), but also a number of rare or even unique domains involved in mRNA capping (nsp14, nsp16) and fidelity control (nsp14). Several smaller subunits (nsp7–nsp10) act as crucial cofactors of these enzymes and contribute to the emerging “nsp interactome.” Understanding the structure, function, and interactions of the RNA-synthesizing machinery of coronaviruses will be key to rationalizing their evolutionary success and the development of improved control strategies. url: https://api.elsevier.com/content/article/pii/S0065352716300471 doi: 10.1016/bs.aivir.2016.08.008 id: cord-300429-b0zev8zb author: Sobocińska, Justyna title: Protein Palmitoylation and Its Role in Bacterial and Viral Infections date: 2018-01-19 words: 13428.0 sentences: 587.0 pages: flesch: 40.0 cache: ./cache/cord-300429-b0zev8zb.txt txt: ./txt/cord-300429-b0zev8zb.txt summary: We highlight recent data on protein S-palmitoylation in pathogens and their hosts obtained owing to the development of methods based on click chemistry and acyl-biotin exchange allowing proteomic analysis of protein lipidation. Given the large variety of chemical reporters preferentially mimicking distinct fatty acids, recent years have witnessed a plethora of chemistry-based proteomic studies not only on palmitoylated but also myristoylated proteins and proteins bearing the GPI anchor, including those of pathogens and immune cells (10, 14, 85, 86, 114) The aBe Method Reveals Protein The envelope is rich in transmembrane, often S-palmitoylated, glycoproteins called spikes, which can bind to cognate receptors on the host cell plasma membrane triggering endocytosis of the virion, mediate subsequent fusion of the viral and cellular membranes allowing entry of the viral genome to the cytoplasm, and are also involved in the budding of newly formed virus particles from the cell. abstract: S-palmitoylation is a reversible, enzymatic posttranslational modification of proteins in which palmitoyl chain is attached to a cysteine residue via a thioester linkage. S-palmitoylation determines the functioning of proteins by affecting their association with membranes, compartmentalization in membrane domains, trafficking, and stability. In this review, we focus on S-palmitoylation of proteins, which are crucial for the interactions of pathogenic bacteria and viruses with the host. We discuss the role of palmitoylated proteins in the invasion of host cells by bacteria and viruses, and those involved in the host responses to the infection. We highlight recent data on protein S-palmitoylation in pathogens and their hosts obtained owing to the development of methods based on click chemistry and acyl-biotin exchange allowing proteomic analysis of protein lipidation. The role of the palmitoyl moiety present in bacterial lipopolysaccharide and lipoproteins, contributing to infectivity and affecting recognition of bacteria by innate immune receptors, is also discussed. url: https://www.ncbi.nlm.nih.gov/pubmed/29403483/ doi: 10.3389/fimmu.2017.02003 id: cord-296794-ml2luc1t author: Sollner, Johannes title: Analysis and prediction of protective continuous B-cell epitopes on pathogen proteins date: 2008-01-07 words: 8006.0 sentences: 387.0 pages: flesch: 41.0 cache: ./cache/cord-296794-ml2luc1t.txt txt: ./txt/cord-296794-ml2luc1t.txt summary: This work assesses in how far correlation between antigenicity, variability, post-translational modifications and protectivity/functional relevance can be put to use in a predictive model without the availability of 3D data. Classification into presumably protective or non-protective epitopes is conducted using three independently determined parameters: predicted B-cell antigenicity, sequence variability and conservation of post-translational modification motifs. These results are relativated later in this work when using only potentially relevant domains of a protein antigen, indicating systematic problems of the way B-cell epitope prediction validation is usually conducted. Briefly, proteins were completely scored for antigenicity/protectivity but amino-acid scores in regions outside domains assumed to be surface exposed were set to 0 thus leading to a generic classification as non-protective. On this compilation protectivity prediction using PCA19 in combination with variability and modification likelihood performed significantly better after domain-accessibility filtering as measured by AROC values, while without filtering performance was comparable (although again slightly better) to antigenicity validation results on the Blythe et.al validation-set. abstract: BACKGROUND: The application of peptide based diagnostics and therapeutics mimicking part of protein antigen is experiencing renewed interest. So far selection and design rationale for such peptides is usually driven by T-cell epitope prediction, available experimental and modelled 3D structure, B-cell epitope predictions such as hydrophilicity plots or experience. If no structure is available the rational selection of peptides for the production of functionally altering or neutralizing antibodies is practically impossible. Specifically if many alternative antigens are available the reduction of required synthesized peptides until one successful candidate is found is of central technical interest. We have investigated the integration of B-cell epitope prediction with the variability of antigen and the conservation of patterns for post-translational modification (PTM) prediction to improve over state of the art in the field. In particular the application of machine-learning methods shows promising results. RESULTS: We find that protein regions leading to the production of functionally altering antibodies are often characterized by a distinct increase in the cumulative sum of three presented parameters. Furthermore the concept to maximize antigenicity, minimize variability and minimize the likelihood of post-translational modification for the identification of relevant sites leads to biologically interesting observations. Primarily, for about 50% of antigen the approach works well with individual area under the ROC curve (AROC) values of at least 0.65. On the other hand a significant portion reveals equivalently low AROC values of < = 0.35 indicating an overall non-Gaussian distribution. While about a third of 57 antigens are seemingly intangible by our approach our results suggest the existence of at least two distinct classes of bioinformatically detectable epitopes which should be predicted separately. As a side effect of our study we present a hand curated dataset for the validation of protectivity classification. Based on this dataset machine-learning methods further improve predictive power to a class separation in an equilibrated dataset of up to 83%. CONCLUSION: We present a computational method to automatically select and rank peptides for the stimulation of potentially protective or otherwise functionally altering antibodies. It can be shown that integration of variability, post-translational modification pattern conservation and B-cell antigenicity improve rational selection over random guessing. Probably more important, we find that for about 50% of antigen the approach works substantially better than for the overall dataset of 57 proteins. Essentially as a side effect our method optimizes for presumably best applicable peptides as they tend to be likely unmodified and as invariable as possible which is answering needs in diagnosis and treatment of pathogen infection. In addition we show the potential for further improvement by the application of machine-learning methods, in particular Random Forests. url: https://www.ncbi.nlm.nih.gov/pubmed/18179690/ doi: 10.1186/1745-7580-4-1 id: cord-287266-sd5izamc author: Song, Zhenhui title: EIF4A2 interacts with the membrane protein of transmissible gastroenteritis coronavirus and plays a role in virus replication date: 2019-04-30 words: 4398.0 sentences: 242.0 pages: flesch: 54.0 cache: ./cache/cord-287266-sd5izamc.txt txt: ./txt/cord-287266-sd5izamc.txt summary: title: EIF4A2 interacts with the membrane protein of transmissible gastroenteritis coronavirus and plays a role in virus replication Using the GST pull-down approach and a CO-IP assay, the M protein was found to interact with porcine intestinal cells via eukaryotic translation initiation factor 4-alpha (EIF4A2), an essential component of the cellular translational machinery. The present study provides mechanistic insight into the interaction between the TGEV M protein and intestinal cells which contributes to the understanding of coronavirus replication and may be useful for the development of novel therapeutic strategies for TGEV infection. In the present study, using yeast two-hybrid screening, seven cellular proteins, including eukaryotic translation initiation factor 4-alpha (EIF4A2), were identified to be M-ligands. Moreover, previous reports have shown that EIF4A2 interacts with VP1 of infectious bursal disease virus (IBD) and inhibits the RNA polymerase activity of IBDV to reduce its replication in host cells (Tacken et al., 2004; Gao et al., 2017) . abstract: Abstract Transmissible gastroenteritis coronavirus (TGEV) is enteropathogenic coronavirus that causes diarrhea in pigs, and is associated with high morbidity and mortality in sucking piglets. The TGEV membrane (M) protein is a decisive protein for the proliferation of viral proteins, and is associated with virus assembly and budding. To identify the cellular proteins that interact with the TGEV M protein, yeast two-hybrid screening was employed, and seven cellular proteins were identified M-binding partners. Using the GST pull-down approach and a CO-IP assay, the M protein was found to interact with porcine intestinal cells via eukaryotic translation initiation factor 4-alpha (EIF4A2), an essential component of the cellular translational machinery. Additionally, confocal microscopy revealed that EIF4A2 and M were colocalized in the cytoplasm. Furthermore, the function of EIF4A2 in intestinal cells during TGEV infection was examined. A knockdown of EIF4A2 by siRNA markedly decreased M protein proliferation and TGEV replication in target cells. Thus demonstrating that EIF4A2 plays a significant role in TGEV replication. The present study provides mechanistic insight into the interaction between the TGEV M protein and intestinal cells which contributes to the understanding of coronavirus replication and may be useful for the development of novel therapeutic strategies for TGEV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/30583231/ doi: 10.1016/j.rvsc.2018.12.005 id: cord-281124-4nhy35xn author: Soowannayan, Chumporn title: RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp date: 2011-08-03 words: 5596.0 sentences: 259.0 pages: flesch: 53.0 cache: ./cache/cord-281124-4nhy35xn.txt txt: ./txt/cord-281124-4nhy35xn.txt summary: To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. In a preliminary attempt to identify an RNA packaging signal in the GAV genome, EMSAs were performed using ssRNAs synthesized to various genome regions including (i) an ORF1b gene 39-region spanning the relative position to the genome packaging signal identified in MHV [28] , (ii) a 39-terminal genome region corresponding in position to the region in the infectious bronchitis virus (IBV) genome reported to contain an RNA binding domain [29] and (iii) the 59-genomic RNA terminus which, in coronaviruses, has also been reported to interact specifically with N protein [30] . abstract: Gill-associated virus (GAV) infects Penaeus monodon shrimp and is the type species okavirus in the Roniviridae, the only invertebrate nidoviruses known currently. Electrophoretic mobility shift assays (EMSAs) using His(6)-tagged full-length and truncated proteins were employed to examine the nucleic acid binding properties of the GAV nucleocapsid (N) protein in vitro. The EMSAs showed full-length N protein to bind to all synthetic single-stranded (ss)RNAs tested independent of their sequence. The ssRNAs included (+) and (−) sense regions of the GAV genome as well as a (+) sense region of the M RNA segment of Mourilyan virus, a crustacean bunya-like virus. GAV N protein also bound to double-stranded (ds)RNAs prepared to GAV ORF1b gene regions and to bacteriophage M13 genomic ssDNA. EMSAs using the five N protein constructs with variable-length N-terminal and/or C-terminal truncations localized the RNA binding domain to a 50 amino acid (aa) N-terminal sequence spanning Met(11) to Arg(60). Similarly to other RNA binding proteins, the first 16 aa portion of this sequence was proline/arginine rich. To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. Moreover, as the synthetic peptide formed higher-order complexes in the presence of RNA, the domain might also play some role in protein/protein interactions stabilizing the helical structure of GAV nucleocapsids. url: https://www.ncbi.nlm.nih.gov/pubmed/21857914/ doi: 10.1371/journal.pone.0022156 id: cord-006331-s2qf98lj author: Spiridonova, V. A. title: Molecular recognition elements: DNA/RNA-aptamers to proteins date: 2010-05-23 words: 7144.0 sentences: 412.0 pages: flesch: 57.0 cache: ./cache/cord-006331-s2qf98lj.txt txt: ./txt/cord-006331-s2qf98lj.txt summary: After 16 rounds of selection from the 2'' amino modified RNA library the isolated aptamers formed a complex with FVIIa characterized by the K d value of 11.3 ± 1.3 nM. performed RNA selection to FIXa; after eight rounds of selection they found an aptamer, which bound to FIXa with the K d value of 0.65 ± 0.2 nM and exhibited 5000 fold higher affinity to FIXa compared with FVIIa, FXa, FXIa and activated protein C [20] . These aptamers formed a complex with ΔNS3 with the K d value of 10 nM, caused 90% inhibition of protease activity of the ΔNS3 peptide and full sized NS3 bound to a maltose binding protein (MBP NS3). Four teen rounds of selection yielded the RNA aptamer, exhibiting high affinity binding to p50 and inhibition of NF kB binding to DNA by preventing protein dimerization [91] . abstract: The review summarizes data on DNA/RNA aptamers, a novel class of molecular recognition elements. Special attention is paid to the aptamers to proteins involved into pathogenesis of wide spread human diseases. These include aptamers to serine proteases, cytokines, influenza viral proteins, immune deficiency virus protein and nucleic acid binding proteins. High affinity and specific binding of aptamers to particular protein targets make them attractive as direct protein inhibitors. They can inhibit pathogenic proteins and data presented here demonstrate that the idea that nucleic acid aptamers can regulate (inhibit) activity of protein targets has been transformed from the stage of basic developments into the stage of realization of practical tasks. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101625/ doi: 10.1134/s1990750810020046 id: cord-300625-fvirvpyl author: Srinivasan, Suhas title: Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins date: 2020-03-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: During its first two and a half months, the recently emerged 2019 novel coronavirus, SARS-CoV-2, has already infected over one-hundred thousand people worldwide and has taken more than four thousand lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge, we leveraged data about the related coronaviruses that is readily available in public databases and integrated these data into a single computational pipeline. As a result, we provide comprehensive structural genomics and interactomics roadmaps of SARS-CoV-2 and use this information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community. url: https://www.ncbi.nlm.nih.gov/pubmed/32218151/ doi: 10.3390/v12040360 id: cord-254909-8zgvovu4 author: Srivastava, Rajneesh title: Serum profiling of leptospirosis patients to investigate proteomic alterations() date: 2012-12-05 words: 5745.0 sentences: 245.0 pages: flesch: 29.0 cache: ./cache/cord-254909-8zgvovu4.txt txt: ./txt/cord-254909-8zgvovu4.txt summary: In this study, we have performed a proteomic analysis of serum samples from leptospirosis patients (n = 6), febrile controls (falciparum malaria) (n = 8) and healthy subjects (n = 18) to obtain an insight about disease pathogenesis and host immune responses in leptospiral infections. During the database search following parameters were specified: human taxonomy, trypsin digestion with one missed cleavage, carbamidomethyl (C) as fixed modification, oxidation (M) as variable modification, peptide mass tolerance set at 75 ppm and MS/MS tolerance of 0.4 Da. Western blot analysis was performed with serum samples from controls (healthy and febrile) and leptospirosis patients (n = 6) to validate the differential expression of some of the target proteins identified in 2DE and 2D-DIGE experiments. Aiming at analysis of host serum proteome alteration due to leptospirosis, we have identified several differentially expressed proteins and modulation of multiple physiological processes and pathways, including inflammation mediated acute phase responses, complement pathways, heterotrimeric G-protein signaling pathway, coagulation cascade and hemostasis in patients suffering from leptospiral infection. abstract: Leptospirosis is a zoonotic infectious disease of tropical, subtropical and temperate zones, which is caused by the pathogenic spirochetes of genus Leptospira. Although this zoonosis is generally not considered as fatal, the pathogen can eventually cause severe infection with septic shock, multi-organ failure and lethal pulmonary hemorrhages leading to mortality. In this study, we have performed a proteomic analysis of serum samples from leptospirosis patients (n = 6), febrile controls (falciparum malaria) (n = 8) and healthy subjects (n = 18) to obtain an insight about disease pathogenesis and host immune responses in leptospiral infections. 2DE and 2D-DIGE analysis in combination with MALDI-TOF/TOF MS revealed differential expression of 22 serum proteins in leptospirosis patients compared to the healthy controls. Among the identified differentially expressed proteins, 8 candidates exhibited different trends compared to the febrile controls. Functional analysis suggested the involvement of differentially expressed proteins in vital physiological pathways, including acute phase response, complement and coagulation cascades and hemostasis. This is the first report of analysis of human serum proteome alterations in leptospirosis patients, which revealed several differentially expressed proteins, including α-1-antitrypsin, vitronectin, ceruloplasmin, G-protein signaling regulator, apolipoprotein A-IV, which have not been reported in context of leptospirosis previously. This study will enhance our understanding about leptospirosis pathogenesis and provide a glimpse of host immunological responses. Additionally, a few differentially expressed proteins identified in this study may further be investigated as diagnostic or prognostic serum biomarkers for leptospirosis. This article is part of a Special Issue entitled: Integrated omics. url: https://www.sciencedirect.com/science/article/pii/S1874391912002138 doi: 10.1016/j.jprot.2012.04.007 id: cord-261961-u4d0vvmq author: St-Germain, Jonathan R. title: A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research date: 2020-08-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Key steps of viral replication take place at host cell membranes, but the detection of membrane-associated protein-protein interactions using standard affinity-based approaches (e.g. immunoprecipitation coupled with mass spectrometry, IP-MS) is challenging. To learn more about SARS-CoV-2 - host protein interactions that take place at membranes, we utilized a complementary technique, proximity-dependent biotin labeling (BioID). This approach uncovered a virus-host topology network comprising 3566 proximity interactions amongst 1010 host proteins, highlighting extensive virus protein crosstalk with: (i) host protein folding and modification machinery; (ii) membrane-bound vesicles and organelles, and; (iii) lipid trafficking pathways and ER-organelle membrane contact sites. The design and implementation of sensitive mass spectrometric approaches for the analysis of complex biological samples is also important for both clinical and basic research proteomics focused on the study of COVID-19. To this end, we conducted a mass spectrometry-based characterization of the SARS-CoV-2 virion and infected cell lysates, identifying 189 unique high-confidence virus tryptic peptides derived from 17 different virus proteins, to create a high quality resource for use in targeted proteomics approaches. Together, these datasets comprise a valuable resource for MS-based SARS-CoV-2 research, and identify novel virus-host protein interactions that could be targeted in COVID-19 therapeutics. url: https://doi.org/10.1101/2020.08.28.269175 doi: 10.1101/2020.08.28.269175 id: cord-329493-ueqlhgn0 author: Stadler, Konrad title: SARS — beginning to understand a new virus date: 2003 words: 5146.0 sentences: 248.0 pages: flesch: 51.0 cache: ./cache/cord-329493-ueqlhgn0.txt txt: ./txt/cord-329493-ueqlhgn0.txt summary: A new infectious disease, known as severe acute respiratory syndrome (SARS), appeared in the Guangdong province of southern China in 2002. When Thiel and colleagues 20 isolated one genomic and eight subgenomic RNAs from the FRA strain and sequenced their 5′ ends, they identified a conserved sequence (5′ACGAAC3′) that was located in coronaviruses: S, spike protein; E, envelope protein; M, membrane glycoprotein; and N, nucleocapsid protein. Alternatively, these antigens could be delivered by DNA immunization by Figure 6 | The S1 domain of SARS-CoV spike is structurally related to group 2 coronaviruses. Schematic representation of cysteine positions in the S1 domains of group 1, 2 and 3 coronaviruses, compared with the SARS-CoV spike protein. The complete genome sequence of a SARS-CoV isolate (FRA) and experimental data on its key RNA elements and protein functions are described. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection abstract: The 114-day epidemic of the severe acute respiratory syndrome (SARS) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralysed the Asian economy. Aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of SARS and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. Here, we review the genomics of the SARS coronavirus (SARS-CoV), its phylogeny, antigenic structure, immune response and potential therapeutic interventions should the SARS epidemic flare up again. url: https://www.ncbi.nlm.nih.gov/pubmed/15035025/ doi: 10.1038/nrmicro775 id: cord-256325-q70rky3r author: Stewart, Cameron R. title: A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease date: 2017-07-04 words: 8310.0 sentences: 409.0 pages: flesch: 43.0 cache: ./cache/cord-256325-q70rky3r.txt txt: ./txt/cord-256325-q70rky3r.txt summary: title: A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease Here we largely focus on findings from two recent RNAi screens to identify protein-coding genes and host-encoded microRNAs impacting the henipavirus infection cycle in human cells. X-ray data have suggested that the methylation of rRNA requires the formation of this complex with involvement of four fibrillarin molecules interacting with different regions of the target rRNAs. The yeast equivalent of fibrillarin, NOP1, has been more extensively studied than the human counterpart but fibrillarin is a well-conserved protein in most organisms, reinforcing the notion that all post-transcriptional processes involving fibrillarin such as chemical modification (methylation) of rRNA, pre-rRNA cleavage and ribosome assembly are essential for proper cellular functioning (Rodriguez-Corona et al. Deffrasnes and colleagues showed that siRNA-mediated knockdown of fibrillarin expression dramatically reduced HeV protein production and viral genome replication but did not impact viral fusion, and that fibrillarin catalytic activity was essential to henipavirus infection. abstract: Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are zoonotic RNA viruses that cause lethal disease in humans and are designated as Biosafety Level 4 (BSL4) agents. Moreover, henipaviruses belong to the same group of viruses that cause disease more commonly in humans such as measles, mumps and respiratory syncytial virus. Due to the relatively recent emergence of the henipaviruses and the practical constraints of performing functional genomics studies at high levels of containment, our understanding of the henipavirus infection cycle is incomplete. In this chapter we describe recent loss-of-function (i.e. RNAi) functional genomics screens that shed light on the henipavirus–host interface at a genome-wide level. Further to this, we cross-reference RNAi results with studies probing host proteins targeted by henipavirus proteins, such as nuclear proteins and immune modulators. These functional genomics studies join a growing body of evidence demonstrating that nuclear and nucleolar host proteins play a crucial role in henipavirus infection. Furthermore these studies will underpin future efforts to define the role of nucleolar host–virus interactions in infection and disease. url: https://doi.org/10.1007/82_2017_28 doi: 10.1007/82_2017_28 id: cord-352172-g0jiaenw author: Stoevesandt, Oda title: Protein microarrays: high-throughput tools for proteomics date: 2014-01-09 words: 7464.0 sentences: 373.0 pages: flesch: 32.0 cache: ./cache/cord-352172-g0jiaenw.txt txt: ./txt/cord-352172-g0jiaenw.txt summary: While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. Protein microarray technology has rapidly developed into one of the most active areas in biotechnology today, and is being increasingly applied for the high-throughput discovery of molecular interactions, profiling of protein expression and monitoring of protein modifications. While genome sequencing and annotations provide comprehensive information on protein-encoding genes, and DNA arrays analyze gene expression at the mRNA level, these technologies need to be complemented by functional proteomic studies in order to better understand protein activities, expression levels and interactions at the system level. A reverse-phase micro array approach has been successfully applied to discover distinct pathway-activation differences among breast cancer cell lines, demonstrating the use of array-based ana lysis for multiple pharmacodynamic biomarkers responding to targeted kinase inhibitors [108] . abstract: Protein microarrays are versatile tools for parallel, miniaturized screening of binding events involving large numbers of immobilized proteins in a time- and cost-effective manner. They are increasingly applied for high-throughput protein analyses in many research areas, such as protein interactions, expression profiling and target discovery. While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. This article reviews recent developments in the generation of protein microarrays and their applications in proteomics and diagnostics. url: https://www.ncbi.nlm.nih.gov/pubmed/19385942/ doi: 10.1586/epr.09.2 id: cord-000479-u87eaaj8 author: Stolf, Beatriz S. title: Protein Disulfide Isomerase and Host-Pathogen Interaction date: 2011-10-11 words: 5990.0 sentences: 297.0 pages: flesch: 41.0 cache: ./cache/cord-000479-u87eaaj8.txt txt: ./txt/cord-000479-u87eaaj8.txt summary: These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intraand interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. Among the many redox sensitive proteins that are altered during the course of different infections, protein disulfide isomerase (PDI-) mediated redox switches have been associated with pathogen attachment-internalization, antigen processing in the ER/phagosome, and the regulation of ROS production by Nox family enzymes. PDI is thought to attach to lipids, glycans, and integral membrane proteins via electrostatic interactions at the cell plasma membrane [14, 15] , where its reductive activity mediates the infection of different pathogens ( Figure 2 , discussed later). Protein disulfide isomerase (PDI) associates with NADPH oxidase and is required for phagocytosis of Leishmania chagasi promastigotes by macrophages abstract: Reactive oxygen species (ROS) production by immunological cells is known to cause damage to pathogens. Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals) functionally regulate different cellular pathways in the host-pathogen interaction. These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intra- and interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. The protein disulfide isomerase (PDI) family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER) and towards the cytosol, a thiol-based redox locus for antigen processing. Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection. A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201685/ doi: 10.1100/2011/289182 id: cord-298922-k568hlf4 author: Sun, Dongbo title: Analysis of protein expression changes of the Vero E6 cells infected with classic PEDV strain CV777 by using quantitative proteomic technique date: 2015-06-15 words: 5192.0 sentences: 244.0 pages: flesch: 48.0 cache: ./cache/cord-298922-k568hlf4.txt txt: ./txt/cord-298922-k568hlf4.txt summary: Among the disease-related functions, certain anti-viral pathways and proteins, such as the RIG-I-like receptor, Rap1, autophagy, mitogen-activated protein kinase, PI3K-Akt and Jak-STAT signaling pathways, and integrin β2/β3 and cystatin-C proteins, represented potential factors in PEDV infection. In our current study, we used a quantitative proteomics approach based on an iTRAQ tandem mass spectrometry (MS/MS) technique to identify proteins differentially expressed between PEDV-infected and mock-infected Vero E6 cells. To verify the differential expression of the selected DEPs, equivalent volumes of the cell lysate replicates from the PEDV-infected (V1-V3) and mock-infected (C1-C3) Vero E6 cells were pooled into the V and C samples, respectively, and western blotting was performed as described above, with the following exceptions: a 1:1000 dilution of the polyclonal antibodies anti-␤ tubulin, anti-integrin-␤3, anti-cystatin-C, anti-protein S100-A2, anti-apolipoprotein E4, and anti-centrin from rabbit (Beijing Biosynthesis Biotechnology, Beijing, China) was used as the primary antibody, and a 1:5000 dilution of the HRP-conjugated goat anti-rabbit IgG (Sigma-Aldrich, St. Louis, USA) was used as the secondary antibody. abstract: Recent outbreaks of porcine epidemic diarrhea virus (PEDV) have caused widespread concern. The identification of proteins associated with PEDV infection might provide insight into PEDV pathogenesis and facilitate the development of novel antiviral strategies. We analyzed the differential protein profile of PEDV-infected Vero E6 cells using mass spectrometry and an isobaric tag for relative and absolute quantification. A total of 126 proteins were identified that were differentially expressed between the PEDV-infected and mock-infected groups (P < 0.05, quantitative ratio ≥1.2), among which the expression of 58 proteins was up-regulated and that of 68 proteins was down-regulated in the PEDV-infected Vero E6 cells, involving in integrin β2/β3, cystatin-C. The Gene Ontology analysis indicated that the molecular function of the differentially expressed proteins (DEPs) was primarily related to binding and catalytic activity, and that the biological functions in which the DEPs are involved included metabolism, organismal systems, cellular processes, genetic information processing, environmental information processing, and diseases. Among the disease-related functions, certain anti-viral pathways and proteins, such as the RIG-I-like receptor, Rap1, autophagy, mitogen-activated protein kinase, PI3K-Akt and Jak-STAT signaling pathways, and integrin β2/β3 and cystatin-C proteins, represented potential factors in PEDV infection. Our findings provide valuable insight into PEDV-Vero E6 cell interactions. url: https://www.sciencedirect.com/science/article/pii/S0166093415000695 doi: 10.1016/j.jviromet.2015.03.002 id: cord-289026-v09m2fzw author: Sun, Yan-gang title: Characterization of the interaction between recombinant porcine aminopeptidase N and spike glycoprotein of porcine epidemic diarrhea virus date: 2018-10-01 words: 5232.0 sentences: 340.0 pages: flesch: 56.0 cache: ./cache/cord-289026-v09m2fzw.txt txt: ./txt/cord-289026-v09m2fzw.txt summary: Infection by its causative agent PED virus (PEDV), an Alpha-coronavirus, was previously proven to be mediated by its spike (S) glycoprotein and a cellular receptor porcine aminopeptidase N (pAPN). We then assayed the purified target proteins through immunogenicity tests, PEDV binding interference assays, circular dichroism (CD) measurements, pAPN activity assay and structural determination, demonstrating that they were biologically functional. Based on the results above, recombinant pAPN ectodomain was obtained as dimers, and PEDV S1 or S1t protein existed as monomers, which showed similar natures of mammalian APN [43] and other coronavirus S proteins [48] [49] [50] as previously reported. In the current study, three canonical assays were carried out to characterize the interaction between pAPN ectodomain and PEDV S1 or S1t protein since these functional target proteins were successfully prepared. Identification and comparison of receptor binding characteristics of the spike protein of two porcine epidemic diarrhea virus strains abstract: Porcine epidemic diarrhea (PED) has caused huge economic losses to the global pork industry. Infection by its causative agent PED virus (PEDV), an Alpha-coronavirus, was previously proven to be mediated by its spike (S) glycoprotein and a cellular receptor porcine aminopeptidase N (pAPN). Interestingly, some recent studies have indicated that pAPN is not a functional receptor for PEDV. To date, there is a lack of a direct evidence for the interaction between pAPN and PEDV S protein in vitro. Here, we prepared pAPN ectodomain and the truncated variants of PEDV S protein in Drosophila S2 cells. These recombinant proteins were homogeneous after purification by metal-affinity and size-exclusion chromatography. We then assayed the purified target proteins through immunogenicity tests, PEDV binding interference assays, circular dichroism (CD) measurements, pAPN activity assay and structural determination, demonstrating that they were biologically functional. Finally, we characterized their interactions by gel filtration chromatography, native-polyacrylamide gel electrophoresis (PAGE) and surface plasmon resonance (SPR) analyses. The results showed that their affinities were too low to form complexes, which suggest that pAPN may be controversial as the genuine receptor for PEDV. Therefore, further research needs to be carried out to elucidate the interaction between PEDV and its genuine receptor. url: https://api.elsevier.com/content/article/pii/S0141813018305300 doi: 10.1016/j.ijbiomac.2018.05.167 id: cord-330715-olypwdoq author: Sun, Zeyu title: Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications date: 2020-08-30 words: 5567.0 sentences: 275.0 pages: flesch: 50.0 cache: ./cache/cord-330715-olypwdoq.txt txt: ./txt/cord-330715-olypwdoq.txt summary: title: Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications In this study, we report a comprehensive N-glycosylation profile-as well as other PTMs-of the HCoV-19 S protein and hACE2, elucidated by high-resolution mass spectrometry (MS) analyses. To resolve glycan camouflage on the surface of the HCoV-19 S protein and hACE2, intact glycopeptides derived from protease digestion and fractionated by HILIC were directly subjected to LC-MSMS analysis specifically designed to detect peptides with extra molecular weight due to N-glycan attachment. Fig. 2 (c) provides a summary of the most dominant N-glycan composition and predicted structure for each site of the HCoV-19 spike protein and hACE2. When the spike proteins from HCoV-19 and SARS-CoV were compared, it was noticeable that the majority of differences in the glycosylation sites occurred in the distal S1 subunit, resulting in a significant difference in the glycan profile in the outermost canopy of the virus formed by spike trimer clusters. abstract: The COVID-19 pandemic has led to worldwide efforts to understand the biological traits of the newly identified HCoV-19 virus. In this mass spectrometry (MS)-based study, we reveal that out of 21 possible glycosites in the HCoV-19 S protein, 20 are completely occupied by N-glycans, predominantly of the oligomannose type. All seven glycosylation sites in human angiotensin I converting enzyme 2 (hACE2) were found to be completely occupied, mainly by complex N-glycans. However, glycosylation did not directly contribute to the binding affinity between HCoV-19 S and hACE2. Additional post-translational modification (PTM) was identified, including multiple methylated sites in both proteins and multiple sites with hydroxylproline in hACE2. Refined structural models of HCoV-19 S and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy (cryo-EM) structures. The PTM and glycan maps of HCoV-19 S and hACE2 provide additional structural details for studying the mechanisms underlying host attachment and the immune response of HCoV-19, as well as knowledge for developing desperately needed remedies and vaccines. url: https://www.sciencedirect.com/science/article/pii/S2095809920302344?v=s5 doi: 10.1016/j.eng.2020.07.014 id: cord-023865-6rafp3x3 author: Surjit, Milan title: The Nucleocapsid Protein of the SARS Coronavirus: Structure, Function and Therapeutic Potential date: 2009-07-22 words: 9210.0 sentences: 448.0 pages: flesch: 45.0 cache: ./cache/cord-023865-6rafp3x3.txt txt: ./txt/cord-023865-6rafp3x3.txt summary: Towards the end of the article, we will also discuss some recent reports regarding the possible clinically relevant use of the nucleocapsid protein, as a candidate diagnostic tool and vaccine against SARS-CoV infection. Interestingly, biochemically mediated inhibition of GSK3 activity in SARS-CoV infected cells also leads to around 80% reduction in viral titer and subsequent induction of a virus-induced cytopathic effect. Further, S-phase specific gene products like cyclin E and CDK2 were found to be downregulated in SARS-CoV infected cell lysate, which suggested that the observed phenomenon may be relevant in vivo. Based on this observation, Palese''s laboratory has studied the IFN inhibitory property of different SARS-CoV proteins, which revealed that ORF3, ORF6 as well as the N-protein have the ability to independently inhibit IFN production through different mechanisms. Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells abstract: As in other coronaviruses, the nucleocapsid protein is one of the core components of the SARS coronavirus (CoV). It oligomerizes to form a closed capsule, inside which the genomic RNA is securely stored thus providing the SARS-CoV genome with its first line of defense from the harsh conditions of the host environment and aiding in replication and propagation of the virus. In addition to this function, several reports have suggested that the SARS-CoV nucleocapsid protein modulates various host cellular processes, so as to make the internal milieu of the host more conducive for survival of the virus. This article will analyze and discuss the available literature regarding these different properties of the nucleocapsid protein. Towards the end of the article, we will also discuss some recent reports regarding the possible clinically relevant use of the nucleocapsid protein, as a candidate diagnostic tool and vaccine against SARS-CoV infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176212/ doi: 10.1007/978-3-642-03683-5_9 id: cord-279106-3ffa9djf author: Syatila Ab Ghani, Nur title: Side chain similarity comparisons for integrated drug repositioning and potential toxicity assessments in epidemic response scenarios: the case for COVID-19 date: 2020-10-21 words: 6970.0 sentences: 404.0 pages: flesch: 52.0 cache: ./cache/cord-279106-3ffa9djf.txt txt: ./txt/cord-279106-3ffa9djf.txt summary: In this work, the three-dimensional arrangements of amino acid side chains in known drug binding sites (substructures) were used to search for similarly arranged sites in SARS-CoV-2 protein structures in the Protein Data Bank for the potential repositioning of approved compounds. The investigations of binding properties in disease-related proteins derived from the comparison of amino acid substructure arrangements allows for effective mechanism driven decision making to rank and select only the compounds with the highest potential for success and safety to be prioritized for clinical trials or treatments. In the case of the COVID-19 pandemic caused by the SARS-CoV-2 virus, we demonstrate that the pipeline can identify candidate compounds quickly and sustainably in combination with associated risk factors derived from the analysis of potential off-target site binding by the compounds to be repurposed. 33 In this work, amino acid side chain similarity searching was utilized to propose alternative target sites in 34 SARS-CoV-2 protein structures for drug repositioning. abstract: Structures of protein-drug-complexes provide an atomic level profile of drug-target interactions. In this work, the three-dimensional arrangements of amino acid side chains in known drug binding sites (substructures) were used to search for similarly arranged sites in SARS-CoV-2 protein structures in the Protein Data Bank for the potential repositioning of approved compounds. We were able to identify 22 target sites for the repositioning of 16 approved drug compounds as potential therapeutics for COVID-19. Using the same approach, we were also able to investigate the potentially promiscuous binding of the 16 compounds to off-target sites that could be implicated in toxicity and side effects that had not been provided by any previous studies. The investigations of binding properties in disease-related proteins derived from the comparison of amino acid substructure arrangements allows for effective mechanism driven decision making to rank and select only the compounds with the highest potential for success and safety to be prioritized for clinical trials or treatments. The intention of this work is not to explicitly identify candidate compounds but to present how an integrated drug repositioning and potential toxicity pipeline using side chain similarity searching algorithms are of great utility in epidemic scenarios involving novel pathogens. In the case of the COVID-19 pandemic caused by the SARS-CoV-2 virus, we demonstrate that the pipeline can identify candidate compounds quickly and sustainably in combination with associated risk factors derived from the analysis of potential off-target site binding by the compounds to be repurposed. url: https://www.ncbi.nlm.nih.gov/pubmed/33101604/ doi: 10.1016/j.csbj.2020.10.013 id: cord-265642-7mu530yp author: Syomin, B. V. title: Virus-Like Particles as an Instrument of Vaccine Production date: 2019-06-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The paper discusses the techniques which are currently implemented for vaccine production based on virus-like particles (VLPs). The factors which determine the characteristics of VLP monomers assembly are provided in detail. Analysis of the literature demonstrates that the development of the techniques of VLP production and immobilization of target antigens on their surface have led to the development of universal platforms which make it possible for virtually any known antigen to be exposed on the particle surface in a highly concentrated form. As a result, the focus of attention has shifted from the approaches to VLP production to the development of a precise interface between the organism’s immune system and the peptides inducing a strong immune response to pathogens or the organism’s own pathological cells. Immunome-specified methods for vaccine design and the prospects of immunoprophylaxis are discussed. Certain examples of vaccines against viral diseases and cancers are considered. url: https://doi.org/10.1134/s0026893319030154 doi: 10.1134/s0026893319030154 id: cord-026012-r0w0jbpg author: TENNANT, BUD C. title: Gastrointestinal Function date: 2014-06-27 words: 19858.0 sentences: 1049.0 pages: flesch: 50.0 cache: ./cache/cord-026012-r0w0jbpg.txt txt: ./txt/cord-026012-r0w0jbpg.txt summary: In the dog, gastric juice is produced in the resting state at a rate of approximately 5 ml/hour (Gray and Bûcher, 1941) , and the composition is similar to that of the basal component, containing practi cally no peptic activity or hydrochloric acid. When the flow of gastric juice is stimulated maximally, the dog may produce 80 ml or more per hour (Gray and Bûcher, 1941) , and this secretion contains large amounts of peptic activity and hydrochloric acid. The endopeptidases and exopep(Table II) , producing free amino acids, which are absorbed directly, or small peptides, which are further hydrolyzed by the aminopeptidases of the intestinal mucosa (see Section III,C). Despite the long interest in and controversy regarding the subject of this section, the relative amounts of the various types of protein digestion products, i.e., peptides and amino acids, which are actually absorbed by intestinal mucosal cells during normal digestion are still not known. abstract: This chapter discusses the functions of gastrointestinal tract. The principal functions of the gastrointestinal tract are assimilation of nutrients and excretion of the waste products of digestion. Within the gastrointestinal tract, these substances are solubilized and degraded enzymatically to simple molecules, sufficiently small in size and in a form that permits absorption across the mucosal epithelium. The distribution of the different types of secretory cells in the salivary glands varies among species. The mandibular and sublingual glands are mixed salivary glands containing both mucous and serous types of cells, and produce a viscous secretion that contains large amounts of mucus. The cytoplasm of the secretory cells contains numerous zymogen granules that vary in size and number depending on the activity of the gland. These granules contain the precursors of the hydrolytic enzymes responsible for digestion of the major dietary components. The cells of the terminal ducts probably secrete the bicarbonate ion responsible for neutralizing hydrochloric acid that enters the duodenum from the stomach. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271190/ doi: 10.1016/b978-0-12-396350-5.50013-9 id: cord-253987-83h861lp author: Tada, Takuya title: A soluble ACE2 microbody protein fused to a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2 infection in cell culture date: 2020-09-17 words: 6830.0 sentences: 349.0 pages: flesch: 50.0 cache: ./cache/cord-253987-83h861lp.txt txt: ./txt/cord-253987-83h861lp.txt summary: The disulfide-bonded ACE2 microbody protein inhibited entry of lentiviral SARS-CoV-2 spike protein pseudotyped virus and live SARS-CoV-2 with a potency 10-fold higher than unmodified soluble ACE2 and was active after initial virus binding to the cell. In SARS-CoV-2 entry, the virus attaches to the target cell through the interaction of the spike glycoprotein (S) with its receptor, the angiotensin-converting enzyme 2 (ACE2) (Li, 2015; Li et al., 2005; Li et al., 2003) , a plasma membrane protein carboxypeptidase that degrades angiotensin II to angiotensin-(1-7) [Ang-(1-7)] a vasodilator that promotes sodium transport in the regulation of cardiac function and blood pressure (Kuba et al., 2010; Riordan, 2003; Tikellis and Thomas, 2012) . To determine the relative antiviral activity of soluble ACE2 and the ACE2 microbody proteins, we tested their ability to block the infection SARS-CoV-2 Δ19 S protein pseudotyped GFP/luciferase reporter virus. abstract: Soluble forms of ACE2 have recently been shown to inhibit SARS-CoV-2 infection. We report on an improved soluble ACE2, termed a “microbody” in which the ACE2 ectodomain is fused to Fc domain 3 of the immunoglobulin heavy chain. The protein is smaller than previously described ACE2-Ig Fc fusion proteins and contains an H345A mutation in the ACE2 catalytic active site that inactivates the enzyme without reducing its affinity for the SARS-CoV-2 spike. The disulfide-bonded ACE2 microbody protein inhibited entry of lentiviral SARS-CoV-2 spike protein pseudotyped virus and live SARS-CoV-2 with a potency 10-fold higher than unmodified soluble ACE2 and was active after initial virus binding to the cell. The ACE2 microbody inhibited the entry of ACE2-specific β coronaviruses and viruses with the high infectivity variant D614G spike. The ACE2 microbody may be a valuable therapeutic for COVID-19 that is active against SARS-CoV-2 variants and future coronaviruses that may arise. url: https://doi.org/10.1101/2020.09.16.300319 doi: 10.1101/2020.09.16.300319 id: cord-333966-st6gyozv author: Taherkhani, Reza title: Design and production of a multiepitope construct derived from hepatitis E virus capsid protein date: 2015-03-17 words: 5199.0 sentences: 255.0 pages: flesch: 51.0 cache: ./cache/cord-333966-st6gyozv.txt txt: ./txt/cord-333966-st6gyozv.txt summary: The aim of this study was to design a high density multiepitope protein, which can be a promising multiepitope vaccine candidate against Hepatitis E virus (HEV). Therefore, the present study was undertaken to design a high density multiepitope protein compromising four HTL epitopes with high-affinity binding to the HLA molecules using the in silico analysis, and to evaluate the immunological properties of this protein in vitro. In brief, approximately 1 Â 10 5 cells/well of PBMCs of each sample in RPMI 1640 and 10% FCS were added to four wells of round-bottom 96-well plates in total volume of 180 ml/well, stimulated with 20 ml/well of truncated ORF2 protein (10 mg/ml), high density multiepitope (10 mg/ml) and Phytohemagglutinin (PHA) (5 mg/ml) (Sigma-Aldrich) separately, and incubated at 37˚C for 4 days. IFN-g ELISPOT responses to high density multiepitope protein and truncated ORF2 protein were found significantly higher in HEV-recovered individuals than control group (P < 0.001). abstract: The aim of this study was to design a high density multiepitope protein, which can be a promising multiepitope vaccine candidate against Hepatitis E virus (HEV). Initially, conserved and antigenic helper T‐lymphocyte (HTL) epitopes in the HEV capsid protein were predicted by in silico analysis. Subsequently, a multiepitope comprising four HTL epitopes with high‐affinity binding to the HLA molecules was designed, and repeated four times as high density multiepitope construct. This construct was synthesized and cloned into pET‐30a (+) vector. Then, it was transformed and expressed in Escherichia coli BL21 cells. The high density multiepitope protein was purified by Ni‐NTA agarose and concentrated using Amicon filters. Finally, the immunological properties of this high density multiepitope protein were evaluated in vitro. The results showed that the high density multiepitope construct was successfully expressed and purified. SDS‐PAGE and Western blot analyses showed the presence of a high density multiepitope protein band of approximately 33 kDa. Approximately 1 mg of the purified protein was obtained from each liter of the culture media. Moreover, the purified multiepitope protein was capable of induction of proliferation responses, IFN‐γ ELISPOT responses and IFN‐γ and IL‐12 cytokines production in a significant level in peripheral blood mononuclear cells (PBMCs) isolated from HEV‐recovered individuals compared to the control group. In conclusion, the newly produced multiepitope protein can induce significant T helper type 1 responses in vitro, and can be considered as a novel strategy for the development of HEV vaccines in the future. J. Med. Virol. 87:1225–1234, 2015. © 2015 Wiley Periodicals, Inc. url: https://doi.org/10.1002/jmv.24171 doi: 10.1002/jmv.24171 id: cord-302414-g5onwhg1 author: Tahir ul Qamar, Muhammad title: Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2 date: 2020-09-16 words: 6780.0 sentences: 434.0 pages: flesch: 47.0 cache: ./cache/cord-302414-g5onwhg1.txt txt: ./txt/cord-302414-g5onwhg1.txt summary: Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast Band Tcell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. The purpose of this study was to pinpoint the potential T-cell and B-cell epitopes from SARS-CoV-2 structural proteins which can be further joined through adjuvant and linkers to design a multiepitope-based subunit vaccine (MESV). Here, we explored the development of epitope-based vaccines targeting the structural proteins (S, M, and E) of the SARS-CoV-2. Taken together, we characterized SARS-CoV-2 structural proteins (S, E, and M) for antigenic epitopes and proposed a potential MESV utilizing various immunoinformatics and computational approaches. abstract: BACKGROUND: Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19. METHODS: Structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) of SARS-CoV-2 are responsible for its prime functions. Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B- and T- cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. RESULTS: Predicted epitopes suggested high antigenicity, conserveness, substantial interactions with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 88.40%. Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers. The MESV construct was non-allergenic, stable, and highly antigenic. Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3 (TLR3). Furthermore, in silico immune simulation revealed significant immunogenic response of MESV. Finally, MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system, to ensure its increased expression. CONCLUSION: The MESV developed in this study is capable of generating immune response against COVID-19. Therefore, if designed MESV further investigated experimentally, it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19. url: https://doi.org/10.1186/s40249-020-00752-w doi: 10.1186/s40249-020-00752-w id: cord-254100-u6x5zd4i author: Taliansky, M.E. title: Involvement of the Plant Nucleolus in Virus and Viroid Infections: Parallels with Animal Pathosystems date: 2010-10-15 words: 13988.0 sentences: 662.0 pages: flesch: 40.0 cache: ./cache/cord-254100-u6x5zd4i.txt txt: ./txt/cord-254100-u6x5zd4i.txt summary: An increasing number of reports reveal that similar to the proteins of animal viruses, many plant virus proteins localize in the nucleolus to divert host nucleolar proteins from their natural functions in order to exert novel role(s) in the virus infection cycle. An increasing number of reports reveal that similar to the proteins of animal viruses, many plant virus proteins localize in the nucleolus to divert host nucleolar proteins from their natural functions in order to exert novel role(s) in the virus infection cycle. As their name suggests, MPs are involved in virus spread in infected plants, and the potential role of fibrillarin in this process will be discussed in Section IV.B. The multifunctional PVA (potato virus A)-encoded viral genomelinked protein (VPg) is also able to interact with fibrillarin (Rajamäki and Bonfiglioli et al. abstract: The nucleolus is a dynamic subnuclear body with roles in ribosome subunit biogenesis, mediation of cell-stress responses, and regulation of cell growth. An increasing number of reports reveal that similar to the proteins of animal viruses, many plant virus proteins localize in the nucleolus to divert host nucleolar proteins from their natural functions in order to exert novel role(s) in the virus infection cycle. This chapter will highlight studies showing how plant viruses recruit nucleolar functions to facilitate virus translation and replication, virus movement and assembly of virus-specific ribonucleoprotein (RNP) particles, and to counteract plant host defense responses. Plant viruses also provide a valuable tool to gain new insights into novel nucleolar functions and processes. Investigating the interactions between plant viruses and the nucleolus will facilitate the design of novel strategies to control plant virus infections. url: https://www.ncbi.nlm.nih.gov/pubmed/20951872/ doi: 10.1016/b978-0-12-385034-8.00005-3 id: cord-336542-6asieplk author: Tanco, Sebastián title: Structure–Function Analysis of the Short Splicing Variant Carboxypeptidase Encoded by Drosophila melanogaster silver date: 2010-08-20 words: 7625.0 sentences: 431.0 pages: flesch: 56.0 cache: ./cache/cord-336542-6asieplk.txt txt: ./txt/cord-336542-6asieplk.txt summary: Overall, DmCPD1Bs conforms to the structure of N/E-type funnelins/M14B metallopeptidases, but it has two unique structural elements potentially involved in regulation of its activity: (i) two contiguous surface cysteines that may become palmitoylated and target the enzyme to membranes, thus providing control through localization, and (ii) a surface hot spot targetable by peptidases that would provide a regulatory mechanism through proteolytic inactivation. Given that the fruit fly possesses orthologs of only two out of the five proteolytically competent N/E-type funnelins found in higher vertebrates, DmCPD1Bs may represent a functional analog of at least one of the missing mammalian CPs. The silver (svr) gene was discovered in Drosophila melanogaster by Bridges in the early 1920s and it maps near the distal end of chromosome X. [3] [4] [5] [6] The long variants possess the overall modular structure and sequence features of carboxypeptidase D (CPD), a glycosylated 180-kDa enzyme studied since the middle 1990s in fruit fly, mouse, rat, duck, bovine, chicken, and humans. abstract: Abstract Drosophila melanogaster silver gene is the ortholog of the coding gene of mammalian carboxypeptidase D (CPD). The silver gene gives rise to eight different splicing variants of differing length that can contain up to three homologous repeats. Among the protein variants encoded, the short form 1B alias DmCPD1Bs (D . melanogaster CPD variant 1B short) is necessary and sufficient for viability of the fruit fly. It has one single repeat, it is active against standard peptide substrates, and it is localized to the secretory pathway. In this work, the enzyme was found as a monomer in solution and as a homodimer in the crystal structure, which features a protomer with an N-terminal 311-residue catalytic domain of α/β-hydrolase fold and a C-terminal 84-residue all-β transthyretin-like domain. Overall, DmCPD1Bs conforms to the structure of N/E-type funnelins/M14B metallopeptidases, but it has two unique structural elements potentially involved in regulation of its activity: (i) two contiguous surface cysteines that may become palmitoylated and target the enzyme to membranes, thus providing control through localization, and (ii) a surface hot spot targetable by peptidases that would provide a regulatory mechanism through proteolytic inactivation. Given that the fruit fly possesses orthologs of only two out of the five proteolytically competent N/E-type funnelins found in higher vertebrates, DmCPD1Bs may represent a functional analog of at least one of the missing mammalian CPs. url: https://doi.org/10.1016/j.jmb.2010.06.035 doi: 10.1016/j.jmb.2010.06.035 id: cord-329403-jzrlywfe author: Teo, Su Hui Catherine title: A NS1-binding monoclonal antibody interacts with two residues that are highly conserved in seasonal as well as newly emerged influenza A virus date: 2019-03-06 words: 4448.0 sentences: 246.0 pages: flesch: 57.0 cache: ./cache/cord-329403-jzrlywfe.txt txt: ./txt/cord-329403-jzrlywfe.txt summary: In this study, we have generated a novel monoclonal antibody (mAb) 19H9 and epitope mapping revealed that two residues, P85 and Y89, of NS1 are essential for interacting with this mAb. Furthermore, residues P85 and Y89 are found to be highly conserved across different IAV subtypes, namely seasonal H1N1 and H3N2, as well as the highly pathogenic H5N1 and H5N6 avian strains. The membrane was then washed and full-length NS1 transfected cell lysates were subjected to IP with mAb 19H9 and protein A agarose beads followed by detection of immunoprecipitated proteins using rabbit anti-Myc antibody in Western blot. To delineate the epitope of NS1 recognized by mAb 19H9, a series of NS1 truncation mutants consisting of residues 1-84, 1-100, 91-230 and 85-230 were generated and their expression levels in transiently transfected 293T cells were verified using an anti-Myc antibody ( Fig. 2A, upper panel) . abstract: The non-structural protein 1 (NS1) of influenza A virus (IAV) is a multifunctional protein that antagonizes host antiviral responses, modulating virus pathogenesis. As such, it serves as a good target for research and diagnostic assay development. In this study, we have generated a novel monoclonal antibody (mAb) 19H9 and epitope mapping revealed that two residues, P85 and Y89, of NS1 are essential for interacting with this mAb. Furthermore, residues P85 and Y89 are found to be highly conserved across different IAV subtypes, namely seasonal H1N1 and H3N2, as well as the highly pathogenic H5N1 and H5N6 avian strains. Indeed, mAb 19H9 exhibits broad cross-reactivity with IAV strains of different subtypes. The binding of mAb 19H9 to residue Y89 was further confirmed by the abrogation of interaction between NS1 and p85β. Additionally, mAb 19H9 also detected NS1 proteins expressed in IAV-infected cells, showing NS1 intracellular localization in the cytoplasm and nucleolus. To our knowledge, mAb 19H9 is the first murine mAb to bind at the juxtaposition between the N-terminal RNA-binding domain and C-terminal effector domain of NS1. It could serve as a useful research tool for studying the conformational plasticity and dynamic changes in NS1. url: https://www.ncbi.nlm.nih.gov/pubmed/30839053/ doi: 10.1093/femspd/ftz012 id: cord-283035-tpqf458q author: Thanthrige-Don, Niroshan title: Analyses of the spleen proteome of chickens infected with Marek''s disease virus date: 2009-08-01 words: 7902.0 sentences: 373.0 pages: flesch: 46.0 cache: ./cache/cord-283035-tpqf458q.txt txt: ./txt/cord-283035-tpqf458q.txt summary: In total, 61 protein spots representing 48 host proteins were detected as either quantitatively (false discovery rate (FDR) ≤ 0.05 and fold change ≥ 2) or qualitatively differentially expressed at least once during different sampling points. A representative gel image showing 2D gel electrophoresis map of the relative locations of spots that displayed significant quantitative differential expression (FDR ≤ 0.05 and fold change ≥ 2) at least once during different sampling times. Comparison of total numbers of significantly differentially expressed protein spots in MDV-infected spleens at various sampling time points. Venn diagram summarizing the spots that were significantly differentially expressed in the spleen tissues of MDV-infected chickens according to their corresponding time of sampling. In the present study, we have profiled the global protein expression changes in the chicken spleen in response to MDV infection at various time points representing the different phases of MDV life cycle. Proteomics analysis of differential expression of cellular proteins in response to avian H9N2 virus infection in human cells abstract: Marek's disease virus (MDV), which causes a lymphoproliferative disease in chickens, is known to induce host responses leading to protection against disease in a manner dependent on genetic background of chickens and virulence of the virus. In the present study, changes in the spleen proteome at 7, 14 and 21 days post-infection in response to MDV infection were studied using two-dimensional polyacrylamide gel electrophoresis. Differentially expressed proteins were identified using one-dimensional liquid chromatography electrospray ionization tandem mass spectrometry (1D LC ESI MS/MS). Comparative analysis of multiple gels revealed that the majority of changes had occurred at early stages of the disease. In total, 61 protein spots representing 48 host proteins were detected as either quantitatively (false discovery rate (FDR) ≤ 0.05 and fold change ≥ 2) or qualitatively differentially expressed at least once during different sampling points. Overall, the proteins identified in the present study are involved in a variety of cellular processes such as the antigen processing and presentation, ubiquitin–proteasome protein degradation (UPP), formation of the cytoskeleton, cellular metabolism, signal transduction and regulation of translation. Notably, early stages of the disease were characterized by changes in the UPP, and antigen presentation. Furthermore, changes indicative of active cell proliferation as well as apoptosis together with significant changes in cytoskeletal components that were observed throughout the experimental period suggested the complexity of the pathogenesis. The present findings provide a basis for further studies aimed at elucidation of the role of these proteins in MDV interactions with its host. url: https://doi.org/10.1016/j.virol.2009.05.020 doi: 10.1016/j.virol.2009.05.020 id: cord-007092-ukqvhzws author: Themsakul, Sirintra title: Secretion of M2e:HBc fusion protein by Lactobacillus casei using Cwh signal peptide date: 2016-09-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ability to serve as a delivery vehicle for various interesting biomolecules makes lactic acid bacteria (LAB) very useful in several applications. In the medical field, recombinant LAB expressing pathogenic antigens at different cellular locations have been used to elicit both mucosal and systemic immune responses. Expression–secretion vectors (ESVs) with a signal peptide (SP) are pivotal for protein expression and secretion. In this study, the genome sequence of Lactobacillus casei ATCC334 was explored for new SPs using bioinformatics tools. Three new SPs of the proteins Cwh, SurA and SP6565 were identified and used to construct an ESV based on our Escherichia coli–L. casei shuttle vector, pRCEID-LC13.9. Functional testing of these constructs with the green fluorescence protein (GFP) gene showed that they could secrete the GFP. The construct with CwhSP showed the highest GFP secretion. Consequently, CwhSP was selected to develop an ESV construct carrying a synthetic gene encoding the extracellular domain of the matrix 2 protein fused with the hepatitis B core antigen (M2e:HBc). This ESV was shown to efficiently express and secrete the M2e:HBc fusion protein. The identified SPs and the developed ESVs can be exploited for expression and secretion of homologous and heterologous proteins in L. casei. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108537/ doi: 10.1093/femsle/fnw209 id: cord-337158-0iw2kcaf author: Tiernan, Hannah title: ATR-FTIR spectroscopy and spectroscopic imaging for the analysis of biopharmaceuticals date: 2020-06-22 words: 7405.0 sentences: 425.0 pages: flesch: 38.0 cache: ./cache/cord-337158-0iw2kcaf.txt txt: ./txt/cord-337158-0iw2kcaf.txt summary: Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy is a label-free, non-destructive technique that can be applied to a vast range of biological applications, from imaging cancer tissues and live cells, to determining protein content and secondary structure composition. This characterisation commonly involves the use of techniques such as liquid chromatography tandem mass spectrometry (LC-MS-MS) to monitor changes in mass, 16 high pressure liquid chromatography (HPLC) to determine impurity profiles of samples, 17 and infrared spectroscopy (IR) to identify impurities and compare biosimilars to the original, ''reference drugs''. 75 ATR-FTIR spectroscopy has also been used extensively to study proteins, in particular biopharmaceuticals, and exciting research has shown the potential applications of it to investigate and monitor changes effectively in PTMs and secondary structures. For example, Grosshans et al used in-line FTIR spectroscopy, along with partial least squares (PLS) analysis, as an effective process analytical tool (PAT) for preparative protein chromatography, they found it to be useful to distinguish and selectively identify proteins based on their secondary structure. abstract: Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy is a label-free, non-destructive technique that can be applied to a vast range of biological applications, from imaging cancer tissues and live cells, to determining protein content and secondary structure composition. This review summarises the recent advances in applications of ATR-FTIR spectroscopy to biopharmaceuticals, the application of this technique to biosimilars, and the current uses of FTIR spectroscopy in biopharmaceutical production. We discuss the use of ATR-FTIR spectroscopic imaging to investigate biopharmaceuticals, and finally, give an outlook on the possible future developments and applications of ATR-FTIR spectroscopy and spectroscopic imaging to this field. Throughout the review comparisons will be made between FTIR spectroscopy and alternative analytical techniques, and areas will be identified where FTIR spectroscopy could perhaps offer a better alternative in future studies. This review focuses on the most recent advances in the field of using ATR-FTIR spectroscopy and spectroscopic imaging to characterise and evaluate biopharmaceuticals, both in an industrial and an academic research based environment. url: https://api.elsevier.com/content/article/pii/S1386142520306156 doi: 10.1016/j.saa.2020.118636 id: cord-013315-plptulfb author: Tilocca, Bruno title: Immunoinformatic-Based Prediction of Candidate Epitopes for the Diagnosis and Control of Paratuberculosis (Johne’s Disease) date: 2020-08-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Paratuberculosis is an infectious disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). MAP is an intracellular pathogen with a possible zoonotic potential since it has been successfully isolated from the intestine and blood of Crohn’s disease patients.Since no cure is available, after the detection of the disease, animal culling is the sole applicable containment strategy. However, the difficult detection of the disease in its subclinical form, facilitates its spread raising the need for the development of effective diagnosis and vaccination strategies. The prompt identification and isolation of the infected animals in the subclinical stage would prevent the spread of the infection.In the present study, an immunoinformatic approach has been used to investigate the immunogenic properties of 10 MAP proteins. These proteins were chosen according to a previously published immunoproteomics approach. For each previously-described immunoreactive protein, we predicted the epitopes capable of eliciting an immune response by binding both B-cells and/or class I MHC antigens. The retrieved peptide sequences were analyzed for their specificity and cross-reactivity. The final aim is to employ the discovered peptides sequences as a filtered library useful for early-stage diagnosis and/or to be used in novel multi-subunit or recombinant vaccine formulations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558617/ doi: 10.3390/pathogens9090705 id: cord-280878-1kt51viz author: To, Janet title: Targeting the Channel Activity of Viroporins date: 2016-01-07 words: 15297.0 sentences: 701.0 pages: flesch: 47.0 cache: ./cache/cord-280878-1kt51viz.txt txt: ./txt/cord-280878-1kt51viz.txt summary: For other viroporins, these studies are still mostly in their infancy, although a highresolution structure of the hepatitis C virus (HCV) p7 protein has been recently described (Ouyang et al., 2013) that may be useful for the rational design of p7 channel inhibitors in the future. Structure and ion channel activity of the human respiratory syncytial virus (hRSV) small hydrophobic protein transmembrane domain The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels NMR structure and ion channel activity of the p7 protein from hepatitis C virus Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells Structure and inhibition of the drug-resistant S31N mutant of the M2 ion channel of influenza A virus abstract: Since the discovery that certain small viral membrane proteins, collectively termed as viroporins, can permeabilize host cellular membranes and also behave as ion channels, attempts have been made to link this feature to specific biological roles. In parallel, most viroporins identified so far are virulence factors, and interest has focused toward the discovery of channel inhibitors that would have a therapeutic effect, or be used as research tools to understand the biological roles of viroporin ion channel activity. However, this paradigm is being shifted by the difficulties inherent to small viral membrane proteins, and by the realization that protein–protein interactions and other diverse roles in the virus life cycle may represent an equal, if not, more important target. Therefore, although targeting the channel activity of viroporins can probably be therapeutically useful in some cases, the focus may shift to their other functions in following years. Small-molecule inhibitors have been mostly developed against the influenza A M2 (IAV M2 or AM2). This is not surprising since AM2 is the best characterized viroporin to date, with a well-established biological role in viral pathogenesis combined the most extensive structural investigations conducted, and has emerged as a validated drug target. For other viroporins, these studies are still mostly in their infancy, and together with those for AM2, are the subject of the present review. url: https://doi.org/10.1016/bs.apcsb.2015.12.003 doi: 10.1016/bs.apcsb.2015.12.003 id: cord-002835-qaogpxy9 author: Too, Issac Horng Khit title: Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis date: 2018-01-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764453/ doi: 10.1371/journal.ppat.1006778 id: cord-292688-w4zvfkyl author: Tooze, Sharon A title: Biogenesis of secretory granules in the trans-Golgi network of neuroendocrine and endocrine cells date: 1998-08-14 words: 8150.0 sentences: 320.0 pages: flesch: 45.0 cache: ./cache/cord-292688-w4zvfkyl.txt txt: ./txt/cord-292688-w4zvfkyl.txt summary: An alternative hypothesis is that there is very little constitutive secretion originating from the TGN of regulated cells, and that most molecules in the biosynthetic pathway exit into ISGs. In the ISG, the non-secretory granule proteins would presumably be sorted from the regulated secretory proteins via interaction with a receptor and removed from the ISG in constitutive-like vesicles. Depending on the cargo, distinct mechanisms could be used for selection to increase the e¤ciency of removal of nonsecretory granule proteins from the maturing ISGs. While the mechanisms involved in the formation of both constitutive and regulated secretory vesicles from the TGN is largely unknown there have been recent reports which suggest that both these budding reactions maybe unique in that they function independently of known coat proteins. In the PC12 cell assay, the same e¡ect was observed with [AlF 4 ] À and several other lines of evidence demonstrated that heterotrimeric GTP-binding proteins are involved in the regulation of post-Golgi vesicle formation (see [71] for review). abstract: Secretory granule formation requires selection of soluble and membrane proteins into nascent secretory granules, and exclusion of proteins not required for the function of secretory granules. Both selection and exclusion presumably can occur in the compartment where assembly of the secretory granule begins, the trans most cisternae of the Golgi complex. Current research focused on the initial stages of secretory granule formation includes a search for the ‘signals’ which may mediate active sorting of components into secretory granules, and the role of aggregation of regulated secretory proteins in sorting. In addition, the temporal sequence of the sorting events in the Golgi, and post-Golgi compartments has gained much attention, as summarized by the alternative but not mutually exclusive ‘sorting for entry’ vs. ‘sorting by retention’ models. ‘Sorting for entry’ which encompasses the most popular models requires selection of cargo and membrane and exclusion of non-secretory granule proteins in the TGN prior to secretory granule formation. ‘Sorting by retention’ stipulates that protein selection or exclusion may occur after secretory granule formation: secretory granule specific components are retained during maturation of the granule while non-secretory granule molecules are removed in vesicles which bud from maturing secretory granules. Finally, some progress has been made in the identification of cytosolic components involved in the budding of nascent secretory granules from the TGN. This review will focus on the recent data concerning the events in secretory granule formation which occur, in the trans-Golgi network. url: https://www.ncbi.nlm.nih.gov/pubmed/9714820/ doi: 10.1016/s0167-4889(98)00059-7 id: cord-017999-saxwqc2j author: Travers, Andrew A. title: Gene Regulation by HMGA and HMGB Chromosomal Proteins and Related Architectural DNA-Binding Proteins date: 2005 words: 6332.0 sentences: 294.0 pages: flesch: 48.0 cache: ./cache/cord-017999-saxwqc2j.txt txt: ./txt/cord-017999-saxwqc2j.txt summary: The eukaryotic abundant high mobility group HMGA and HMGB proteins can act as architectural transcription factors by promoting the assembly of higher-order protein-DNA complexes which can either activate or repress gene expression. Similarly rat SSRPl has been shown to facilitate the DNA binding of serum response factor and human SSRPl is associated with the y isoform of p63 in vivo at the endogenous MDM22inAp2nfl''"^^ promoters.^^ In most of these cases, the interaction of the HMG protein with the transcription factor has been detected in vitro and could, in principle, serve as the mechanism for recruitment of HMGB 1 or 2 to particular DNA sites. abstract: The eukaryotic abundant high mobility group HMGA and HMGB proteins can act as architectural transcription factors by promoting the assembly of higher-order protein-DNA complexes which can either activate or repress gene expression. The structural organisation of both classes of protein is similar with either a single or repeated DNA binding domain preceding a short negatively charged C-terminal tail. In the HMGB class of proteins the HMG DNA-binding domain binds non-specifically and introduces a sharp bend into DNA whereas the AT-hook in the HMGA protein binds preferentially to A/T rich regions of DNA and stabilises a B-DNA structure. The acidic tails are hypothesised to facilitate the interaction of the proteins with nudeosomes by binding to the positively charged histone tails. Both classes of protein also interact with a large number of transcription factors that bind to specific DNA sequences. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122717/ doi: 10.1007/0-387-29148-2_11 id: cord-012878-j9vndxgg author: Tremblay, Reynald title: High-yield expression of recombinant soybean agglutinin in plants using transient and stable systems date: 2010-06-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Soybean agglutinin (SBA) is a specific N-acetylgalactosamine-binding plant lectin that can agglutinate a wide variety of cells. SBA has great potential for medical and biotechnology-focused applications, including screening and treatment of breast cancer, isolation of fetal cells from maternal blood for genetic screening, the possibility as a carrier system for oral drug delivery, and utilization as an affinity tag for high-quality purification of tagged proteins. The success of these applications, to a large degree, critically depends on the development of a highly efficient expression system for a source of recombinant SBA (rSBA). Here, we demonstrate the utility of transient and stable expression systems in Nicotiana benthamiana and potato, respectively, for the production of rSBA, with the transgenic protein accumulated to 4% of total soluble protein (TSP) in Nicotiana benthamiana leaves and 0.3% of TSP in potato tubers. Furthermore, we show that both plant-derived rSBAs retain their ability to induce the agglutination of red blood cells, are similarly glycosylated when compared with native SBA, retained their binding specificity for N-acetylgalactosamine, and were highly resistant to degradation in simulated gastric and intestinal fluids. Affinity column purification using N-acetylgalactosamine as a specific ligand resulted in high recovery and purity of rSBA. This work is the first step toward use of rSBA for various new applications, including the development of rSBA as a novel affinity tag for simplified purification of tagged proteins and as a new carrier molecule for delivery of oral drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11248-010-9419-0) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477883/ doi: 10.1007/s11248-010-9419-0 id: cord-351559-az4pgi9k author: Turjya, Rafeed Rahman title: Perversely expressed long noncoding RNAs can alter host response and viral proliferation in SARS-CoV-2 infection date: 2020-06-29 words: 2438.0 sentences: 173.0 pages: flesch: 48.0 cache: ./cache/cord-351559-az4pgi9k.txt txt: ./txt/cord-351559-az4pgi9k.txt summary: Regulatory roles of long non-coding RNAs (lncRNAs) during viral infection and associated antagonism of host antiviral immune responses has become more evident in last decade. To elucidate possible functions of lncRNAs in the COVID-19 pathobiology, we have utilized RNA-seq dataset of SARS-CoV-2 infected lung epithelial cells. By network enrichment analysis we find that these lncRNAs can directly interact with differentially expressed protein-coding genes ADAR, EDN1, KYNU, MALL, TLR2 and YWHAG; and also AKAP8L, EXOSC5, GDF15, HECTD1, LARP4B, LARP7, MIPOL1, UPF1, MOV10 and PRKAR2A, host genes that interact with SARS-CoV-2 proteins. Conclusions Our investigation determines that deregulated lncRNAs in SARS-CoV-2 infection are involved in viral proliferation, cellular survival, and immune response, ultimately determining disease outcome and this information could drive the search for novel RNA therapeutics as a treatment option. abstract: Background Since December 2019, the world is experiencing an unprecedented crisis due to a novel coronavirus, SARS-CoV-2. Owing to poor understanding of pathogenicity, the virus is eluding treatment and complicating recovery. Regulatory roles of long non-coding RNAs (lncRNAs) during viral infection and associated antagonism of host antiviral immune responses has become more evident in last decade. To elucidate possible functions of lncRNAs in the COVID-19 pathobiology, we have utilized RNA-seq dataset of SARS-CoV-2 infected lung epithelial cells. Results Our analyses uncover 21 differentially expressed lncRNAs whose functions are broadly involved in cell survival and regulation of gene expression. By network enrichment analysis we find that these lncRNAs can directly interact with differentially expressed protein-coding genes ADAR, EDN1, KYNU, MALL, TLR2 and YWHAG; and also AKAP8L, EXOSC5, GDF15, HECTD1, LARP4B, LARP7, MIPOL1, UPF1, MOV10 and PRKAR2A, host genes that interact with SARS-CoV-2 proteins. These genes are involved in cellular signaling, metabolism, immune response and RNA homeostasis. Since lncRNAs have been known to sponge microRNAs and protect expression of upregulated genes, we also identified 9 microRNAs that are induced in viral infections; however, some lncRNAs are able to block their usual suppressive effect on overexpressed genes and consequently contribute to host defense and cell survival. Conclusions Our investigation determines that deregulated lncRNAs in SARS-CoV-2 infection are involved in viral proliferation, cellular survival, and immune response, ultimately determining disease outcome and this information could drive the search for novel RNA therapeutics as a treatment option. url: https://doi.org/10.1101/2020.06.29.177204 doi: 10.1101/2020.06.29.177204 id: cord-257802-vgizgq2y author: Uttamchandani, Mahesh title: Applications of microarrays in pathogen detection and biodefence date: 2008-11-12 words: 6568.0 sentences: 305.0 pages: flesch: 35.0 cache: ./cache/cord-257802-vgizgq2y.txt txt: ./txt/cord-257802-vgizgq2y.txt summary: Advances in miniaturizing this initial PCR step, for instance the development of Review Glossary Biodefence: defensive measures against biological threats, including natural/ emerging pathogens and bioterror agents, that have significant potential to endanger public health Detection: identifying the presence of target pathogen(s) from clinical or environmental samples. (b) Antibody microarrays can be used to detect pathogen proteins or antigens that might be present in environmental samples as an indication of contamination or for diagnostic purposes to determine pathogen infection in human tissues. fabricated a customized Affymetrix microarray containing 53 660 probes to detect DNA amplified from 18 different pathogenic microorganisms simultaneously, including pathogens from the US CDC''s list of bioterrorism agents, such as Bacillus anthracis (which causes anthrax), Clostridium botulinum (which generates the botulinum toxin), Yersinia pestis (which causes bubonic plague) and the Ebola virus [17] . abstract: The microarray is a platform with wide-ranging potential in biodefence. Owing to the high level of throughput attainable through miniaturization, microarrays have accelerated the ability to respond in an epidemic or crisis. Extending beyond diagnostics, recent studies have applied microarrays as a research tool towards understanding the etiology and pathogenicity of dangerous pathogens, as well as in vaccine development. The original emphasis was on DNA microarrays, but the range now includes protein, antibody and carbohydrate microarrays, and research groups have exploited this diversity to further extend microarray applications in the area of biodefence. Here, we discuss the impact and contributions of the growing range of microarrays and emphasize the concepts that might shape the future of biodefence research. url: https://doi.org/10.1016/j.tibtech.2008.09.004 doi: 10.1016/j.tibtech.2008.09.004 id: cord-301827-a7hnuxy5 author: Uversky, Vladimir N title: A decade and a half of protein intrinsic disorder: Biology still waits for physics date: 2013-04-29 words: 20971.0 sentences: 1059.0 pages: flesch: 43.0 cache: ./cache/cord-301827-a7hnuxy5.txt txt: ./txt/cord-301827-a7hnuxy5.txt summary: 94 Therefore, the abundance and peculiarities of the charged residues distribution within the protein sequences might determine physical and biological properties of extended IDPs and IDPRs. Also, simple polymer physics-based reasoning can give reasonably well-justified explanation of the conformational behavior of extended IDPs. In general, the conformational behavior of IDPs is characterized by the low cooperativity (or the complete lack thereof) of the denaturant-induced unfolding, lack of the measurable excess heat absorption peak(s) characteristic for the melting of ordered proteins, "turned out" response to heat and changes in pH, and the ability to gain structure in the presence of various binding partners. 183 This analysis revealed that proteins involved in regulation and execution of PCD possess substantial amount of intrinsic disorder and IDPRs were implemented in a number of crucial functions, such as protein-protein interactions, interactions with other partners including nucleic acids and other ligands, were shown to be enriched in post-translational modification sites, and were characterized by specific evolutionary patterns. abstract: The abundant existence of proteins and regions that possess specific functions without being uniquely folded into unique 3D structures has become accepted by a significant number of protein scientists. Sequences of these intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number of specific features, such as low overall hydrophobicity and high net charge which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic volumes, low contents of ordered secondary structure, and are characterized by high structural heterogeneity. They are very flexible, but some may undergo disorder to order transitions in the presence of natural ligands. The degree of these structural rearrangements varies over a very wide range. IDPs/IDPRs are tightly controlled under the normal conditions and have numerous specific functions that complement functions of ordered proteins and domains. When lacking proper control, they have multiple roles in pathogenesis of various human diseases. Gaining structural and functional information about these proteins is a challenge, since they do not typically “freeze” while their “pictures are taken.” However, despite or perhaps because of the experimental challenges, these fuzzy objects with fuzzy structures and fuzzy functions are among the most interesting targets for modern protein research. This review briefly summarizes some of the recent advances in this exciting field and considers some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs. url: https://doi.org/10.1002/pro.2261 doi: 10.1002/pro.2261 id: cord-306904-8iteddug author: Uversky, Vladimir N title: Unreported intrinsic disorder in proteins: Building connections to the literature on IDPs date: 2014-12-12 words: 18422.0 sentences: 1012.0 pages: flesch: 48.0 cache: ./cache/cord-306904-8iteddug.txt txt: ./txt/cord-306904-8iteddug.txt summary: 86 Figure 8C represents the results of the computational disorder analysis in human APC (UniProt ID: P04070) and shows that mentioned loops enriched in basic residues are predicted to be disordered or very flexible, thereby providing an interesting mechanistic plane for the molecular basis of APC recognition and binding of FVIII. 96 Figure 8E shows that although human PECAM-1 (UniProt ID: P16284) is predicted to be mostly ordered, the residues, phosphorylation of which is crucial for its function (Y 663 and Y 686 ), are located within the highly disordered C-terminal tail. 210 Figure 14C represents the results of the disorder analysis of human AMSH (UniProt ID: O95630) and shows that this protein contains a long IDPR (residues 90-250) thereby illustrating that the N-terminal part of the analyzed catalytic domain is predicted to be disordered. [222] [223] [224] Figure 14D shows that human Purb protein (UniProt ID: O35295) is predicted to possess significant amount of functionally important intrinsic disorder. abstract: This review opens a new series entitled “Unreported intrinsic disorder in proteins.” The goal of this series is to bring attention of researchers to an interesting phenomenon of missed (or overlooked, or ignored, or unreported) disorder. This series serves as a companion to “Digested Disorder” which provides a quarterly review of papers on intrinsically disordered proteins (IDPs) found by standard literature searches. The need for this alternative series results from the observation that there are numerous publications that describe IDPs (or hybrid proteins with ordered and disordered regions) yet fail to recognize many of the key discoveries and publications in the IDP field. By ignoring the body of work on IDPs, such publications often fail to relate their findings to prior discoveries or fail to explore the obvious implications of their work. Thus, the goal of this series is not only to review these very interesting and important papers, but also to point out how each paper relates to the IDP field and show how common tools in the IDP field can readily take the findings in new directions or provide a broader context for the reported findings. url: https://doi.org/10.4161/21690693.2014.970499 doi: 10.4161/21690693.2014.970499 id: cord-310847-63gh2tg4 author: Uversky, Vladimir N title: The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins date: 2013-04-01 words: 19431.0 sentences: 1043.0 pages: flesch: 50.0 cache: ./cache/cord-310847-63gh2tg4.txt txt: ./txt/cord-310847-63gh2tg4.txt summary: 5, 10, 46 In fact, in comparison with ordered proteins, IDPs/IDPRs are characterized by noticeable biases in their amino acid compositions, 5, 8, 10, [46] [47] [48] containing less of so-called "order-promoting" residues (cysteine, tryptophan, isoleucine, tyrosine, phenylalanine, leucine, histidine, valine, asparagines and methionine, which are mostly hydrophobic residues which are commonly found within the hydrophobic cores of foldable proteins) and more of "disorder-promoting" residues (lysine, glutamine, serine, glutamic acid and proline, which are mostly polar and charged residues, which are typically located at the surface of foldable proteins) (Fig. 1A) . Glutamic acid is an important functional residue of ordered proteins, where it can be involved in the formation of specific electrostatic valves inside the pores of ion channels, or can play unique catalytic roles in the active sites abstract: The ability of a protein to fold into unique functional state or to stay intrinsically disordered is encoded in its amino acid sequence. Both ordered and intrinsically disordered proteins (IDPs) are natural polypeptides that use the same arsenal of 20 proteinogenic amino acid residues as their major building blocks. The exceptional structural plasticity of IDPs, their capability to exist as heterogeneous structural ensembles and their wide array of important disorder-based biological functions that complements functional repertoire of ordered proteins are all rooted within the peculiar differential usage of these building blocks by ordered proteins and IDPs. In fact, some residues (so-called disorder-promoting residues) are noticeably more common in IDPs than in sequences of ordered proteins, which, in their turn, are enriched in several order-promoting residues. Furthermore, residues can be arranged according to their “disorder promoting potencies,” which are evaluated based on the relative abundances of various amino acids in ordered and disordered proteins. This review continues a series of publications on the roles of different amino acids in defining the phenomenon of protein intrinsic disorder and concerns glutamic acid, which is the second most disorder-promoting residue. url: https://doi.org/10.4161/idp.24684 doi: 10.4161/idp.24684 id: cord-319609-y0gdjn64 author: Van Duyne, Rachel title: The identification of unique serum proteins of HIV-1 latently infected long-term non-progressor patients date: 2010-07-06 words: 8544.0 sentences: 356.0 pages: flesch: 47.0 cache: ./cache/cord-319609-y0gdjn64.txt txt: ./txt/cord-319609-y0gdjn64.txt summary: In particular, the analysis of HIV-1 infected serum is an attractive medium with which to identify altered protein expression due to the ease and non-invasive methods of collecting samples as well as the corresponding insight into the in vivo interaction of the virus with infected cells/tissue. We have analyzed and compared serum samples from HIV-1 infected subjects who are being treated using highly active antiretroviral therapy (HAART) to those who are latently infected but have not progressed to AIDS despite the absence of treatment, i.e. long term non-progressors (LTNPs). In order to gain insight into the reason why p16 INK4A may be present preferentially in the serum of LTNP patients, we treated latently infected HIV-1 cell lines (J1.1 and U1) with exogenous purified GST-p16 INK4A Figure 4A depicts an RT assay which measures the viral reverse transcriptase activity of infected cells and is an indicator of functional particle production. abstract: BACKGROUND: The search for disease biomarkers within human peripheral fluids has become a favorable approach to preventative therapeutics throughout the past few years. The comparison of normal versus disease states can identify an overexpression or a suppression of critical proteins where illness has directly altered a patient's cellular homeostasis. In particular, the analysis of HIV-1 infected serum is an attractive medium with which to identify altered protein expression due to the ease and non-invasive methods of collecting samples as well as the corresponding insight into the in vivo interaction of the virus with infected cells/tissue. The utilization of proteomic techniques to globally identify differentially expressed serum proteins in response to HIV-1 infection is a significant undertaking that is complicated due to the innate protein profile of human serum. RESULTS: Here, the depletion of 12 of the most abundant serum proteins, followed by two-dimensional gel electrophoresis coupled with identification of these proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, has allowed for the identification of differentially expressed, low abundant serum proteins. We have analyzed and compared serum samples from HIV-1 infected subjects who are being treated using highly active antiretroviral therapy (HAART) to those who are latently infected but have not progressed to AIDS despite the absence of treatment, i.e. long term non-progressors (LTNPs). Here we have identified unique serum proteins that are differentially expressed in LTNP HIV-1 patients and may contribute to the ability of these patients to combat HIV-1 infection in the absence of HAART. We focused on the cdk4/6 cell cycle inhibitor p16(INK4A )and found that the treatment of HIV-1 latently infected cell lines with p16(INK4A )decreases viral production despite it not being expressed endogenously in these cells. CONCLUSIONS: Identification of these unique proteins may serve as an indication of altered viral states in response to infection as well as a natural phenotypic variability in response to HIV-1 infection in a given population. url: https://doi.org/10.1186/1742-6405-7-21 doi: 10.1186/1742-6405-7-21 id: cord-243806-26n22jbx author: Vandelli, Andrea title: Structural analysis of SARS-CoV-2 and prediction of the human interactome date: 2020-03-30 words: 5252.0 sentences: 317.0 pages: flesch: 52.0 cache: ./cache/cord-243806-26n22jbx.txt txt: ./txt/cord-243806-26n22jbx.txt summary: Here, we performed sequence and structural alignments among 62 SARS-CoV-2 strains and identified the conservation of specific elements in the spike S region, which provides clues on the evolution of domains involved in the binding to ACE2 and sialic acid. As highly structured regions of RNA molecules have strong propensity to form stable contacts with proteins 14 and promote assembly of specific complexes 15, 16 , SARS-CoV-2 domains enriched in double-stranded content are expected to establish interactions within host cells that are important to replicate the virus 17 . Analysis of functional annotations carried out with GeneMania 46 revealed that proteins interacting with the 5'' of SARS-CoV-2 RNA are associated with regulatory pathways involving NOTCH2, MYC and MAX that have been previously connected to viral infection processes ( Fig. 4E) 47, 48 . abstract: Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of>2500 coronaviruses and computed>100000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the 3 and 5 prime ends are the most structured elements in the viral genome and the 5 prime end has the strongest propensity to associate with human proteins. The domain encompassing nucleotides 23000-24000 is highly conserved both at the sequence and structural level, while the region upstream varies significantly. These two sequences code for a domain of the viral protein Spike S that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) and has the potential to bind sialic acids. Our predictions indicate that the first 1000 nucleotides in the 5 prime end can interact with proteins involved in viral RNA processing such as double-stranded RNA specific editases and ATP-dependent RNA-helicases, in addition to other high-confidence candidate partners. These interactions, previously reported to be also implicated in HIV, reveal important information on host-virus interactions. The list of transcriptional and post-transcriptional elements recruited by SARS-CoV-2 genome provides clues on the biological pathways associated with gene expression changes in human cells. url: https://arxiv.org/pdf/2003.13655v4.pdf doi: nan id: cord-284648-yznlgzir author: Varanko, Anastasia title: Recent trends in protein and peptide-based biomaterials for advanced drug delivery date: 2020-08-29 words: 33501.0 sentences: 1732.0 pages: flesch: 42.0 cache: ./cache/cord-284648-yznlgzir.txt txt: ./txt/cord-284648-yznlgzir.txt summary: Albumin is the most abundant protein in human plasma and has a set of properties that make it a unique molecular carrier for drugs: (i) it is a natural physiological carrier of native ligands and nutrients; (ii) it bypasses systemic clearance and degradation by the body''s own innate mechanisms, so that it has an exceptionally long half-life of 19 days in humans, and similarly long half-lives in most animal species [123] [124] [125] [126] ; (iii) it preferentially accumulates at sites of vascular leakiness; (iv) it is highly internalized and metabolized by rapidly growing, nutrient-starved cancer cells; and (v) it is biodegradable and has no known systemic toxicity. Other notable examples of albumin-based delivery systems involve the genetic fusion of ABD to various therapeutic proteins including affibodies [165, 166] , human soluble complement receptor type 1 [167] , single chain antibody-drug conjugates [168] , insulin-like growth factor II [169] , immunotoxins [170] , and respiratory syncytial virus subgroup A (RSV-A) G protein (G2Na) [171] . abstract: nan url: https://doi.org/10.1016/j.addr.2020.08.008 doi: 10.1016/j.addr.2020.08.008 id: cord-031937-qhlatg84 author: Verma, Anukriti title: Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach date: 2020-09-15 words: 6760.0 sentences: 326.0 pages: flesch: 31.0 cache: ./cache/cord-031937-qhlatg84.txt txt: ./txt/cord-031937-qhlatg84.txt summary: In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. The contributions of the microorganisms in the co-evolved IBD and ReA as part of the disease network was created through the interactive maps of the essential host interaction proteins (verified using literature survey) and the information processed through gene expression data analysis 64 . The pathways of the above host interacting proteins were found out using KEGG database that provides ontologies for proteins related to biological processes 67 www.nature.com/scientificreports/ Subsequently, the role of drugs or inhibitors used to suppress the effect of IBD and ReA such as indomethacin, prednisone, ciprofloxacin, sulfasalazine, azathioprine, methotrexate and hydroxychloroquine was scored in the disease network through their docking studies against the potential targets (both host as well microbial targets) as per published methodologies 68, 69 . abstract: Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g. Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia have been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe ‘interspecies communication’, using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA. Our study identified Na((+))/H((+)) anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492238/ doi: 10.1038/s41598-020-71674-8 id: cord-029747-8f463wz0 author: Viedma-Poyatos, Álvaro title: Type III intermediate filaments as targets and effectors of electrophiles and oxidants date: 2020-07-17 words: 12680.0 sentences: 612.0 pages: flesch: 34.0 cache: ./cache/cord-029747-8f463wz0.txt txt: ./txt/cord-029747-8f463wz0.txt summary: The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modifications by oxidants and electrophiles, for which their conserved cysteine residue emerges as a hot spot. Appearance of carbonyl groups on proteins can occur by several mechanisms, including oxidation of amino acid lateral chains, oxidative deamination or formation of certain adducts with compounds that retain a free carbonyl group, as in some types of lipoxidation, like Michael addition of cyPG or of HNE, or after glycation or glycoxidation. Early studies using cytoskeleton preparations from several cell types subjected to oxidative in vitro crosslinking with Cu 2+ -phenanthroline showed the formation of homo-and heterodimers of either vimentin and desmin or vimentin and GFAP, which led to propose that both proteins were present in hybrid filaments [85, 86] . abstract: Intermediate filaments (IFs) play key roles in cell mechanics, signaling and homeostasis. Their assembly and dynamics are finely regulated by posttranslational modifications. The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modifications by oxidants and electrophiles, for which their conserved cysteine residue emerges as a hot spot. Pathophysiological examples of these modifications include lipoxidation in cell senescence and rheumatoid arthritis, disulfide formation in cataracts and nitrosation in endothelial shear stress, although some oxidative modifications can also be detected under basal conditions. We previously proposed that cysteine residues of vimentin and GFAP act as sensors for oxidative and electrophilic stress, and as hinges influencing filament assembly. Accumulating evidence indicates that the structurally diverse cysteine modifications, either per se or in combination with other posttranslational modifications, elicit specific functional outcomes inducing distinct assemblies or network rearrangements, including filament stabilization, bundling or fragmentation. Cysteine-deficient mutants are protected from these alterations but show compromised cellular performance in network assembly and expansion, organelle positioning and aggresome formation, revealing the importance of this residue. Therefore, the high susceptibility to modification of the conserved cysteine of type III IFs and its cornerstone position in filament architecture sustains their role in redox sensing and integration of cellular responses. This has deep pathophysiological implications and supports the potential of this residue as a drug target. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381704/ doi: 10.1016/j.redox.2020.101582 id: cord-016095-jop2rx61 author: Vignais, Pierre V. title: Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century date: 2010-06-08 words: 42843.0 sentences: 1503.0 pages: flesch: 43.0 cache: ./cache/cord-016095-jop2rx61.txt txt: ./txt/cord-016095-jop2rx61.txt summary: Instead of setting out to discover unknown mechanisms by analyzing effects that are dependent on specific causes, with some uncertainty as to the possible success of the enterprise being undertaken, which is the foundation stone of the Bernardian paradigm of the experimental method, many current research projects give themselves achievable and programmable objectives that depend upon the means available to them: sequencing of genomes with a view to comparing them, recognition of sequence similarities in proteins coded for by genes belonging to different species, with the aim of putting together phylogenetic trees, synthesis of interesting proteins in transgenic animals and plants, analysis of the three-dimensional structure of proteins, in order to find sites that are likely to fix medicinal substances, and synthesis of molecular species able to recognize pathogenic targets. abstract: “We can talk endlessly about moral progress, about social progress, about poetic progress, about progress made in happiness; nevertheless, there is a type of progress that defies any discussion, and that is scientific progress, as soon as we judge it within the hierarchy of knowledge, from a specifically intellectual point of view.” url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120277/ doi: 10.1007/978-90-481-3767-1_5 id: cord-002179-v8lpw4r7 author: Viktorovskaya, Olga V. title: Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements date: 2016-08-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication. METHODOLOGY/PRINCIPAL FINDINGS: Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated. CONCLUSIONS/SIGNIFICANCE: The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps cellular proteins for efficient amplification. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996428/ doi: 10.1371/journal.pntd.0004921 id: cord-048360-n9sih438 author: Villard, Viviane title: Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif date: 2007-07-25 words: 4794.0 sentences: 228.0 pages: flesch: 45.0 cache: ./cache/cord-048360-n9sih438.txt txt: ./txt/cord-048360-n9sih438.txt summary: To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. Here, we focus on the Pf parasite erythrocytic stage, a target of protective antibodies and describe a straightforward, rapid procedure based on bioinformatic analysis of a-helical coiled-coil motifs and peptide synthesis. With regard to the structural features and cellular location prediction of the proteins corresponding to the peptides selected for ADCI assays ( Table 1) , 15 of the proteins contain a pentapeptide conforming to the PEXEL consensus [19, 20; 21, 22] , but that none of these have a position within the amino acid sequence that conforms to the location of known active PEXEL motifs (see Materials and Methods and membrane segments, and none of them has a GPI anchor. In conclusion, an approach combining a genome-wide search by bioinformatics of a-helical coiled coil protein motifs and chemical synthesis can lead to the rapid identification and development of new malaria vaccine candidates. abstract: To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920550/ doi: 10.1371/journal.pone.0000645 id: cord-304306-rxjahqwh author: Vlachakis, Dimitrios title: Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic date: 2020-10-08 words: 8517.0 sentences: 459.0 pages: flesch: 48.0 cache: ./cache/cord-304306-rxjahqwh.txt txt: ./txt/cord-304306-rxjahqwh.txt summary: The currently available antiviral option for hospitalized patients is remdesivir, which may inhibit the replication process by targeting the RdRp. Previously proposed treatments for hospitalized patients included hydroxychloroquine, which thought to disrupt virus endocytosis, and lopinavir/ritonavir, which thought to inhibit SARs-CoV-2 main protease (Astuti and Ysrafil, 2020; Magro, 2020) . Silibilin is predicted to have a dual activity against SARS-CoV-2 infection; silibilin can potentially reduce viral replication activity by targeting NSP12 as a remdesivir-like inhibitor, and modulate inflammatory responses by direct inhibition of STAT3 (BoschBarrera et al., 2020) . A recombinant form of the human ACE2 protein was synthesized as a therapeutic treatment for COVID-19, functioning as a decoy for SARS-CoV-2 and essentially preventing the virus from binding to the cell surface ACE2 (Schuster et al., 2010) . Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response abstract: The novel coronavirus SARS-CoV-2 has emerged as a severe threat against public health and global economies. COVID-19, the disease caused by this virus, is highly contagious and has led to an ongoing pandemic. SARS-CoV-2 affects, mainly, the respiratory system, with most severe cases primarily showcasing acute respiratory distress syndrome. Currently, no targeted therapy exists, and since the number of infections and death toll keeps rising, it has become a necessity to study possible therapeutic targets. Antiviral drugs can target various stages of the viral infection, and in the case of SARS-CoV-2, both structural and non-structural proteins have been proposed as potential drug targets. This review focuses on the most researched SARS-CoV-2 proteins, their structure, function, and possible therapeutic approaches. url: https://doi.org/10.1016/j.fct.2020.111805 doi: 10.1016/j.fct.2020.111805 id: cord-307731-a2fqmaly author: Vázquez, Javier title: Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches date: 2020-10-15 words: 11908.0 sentences: 594.0 pages: flesch: 39.0 cache: ./cache/cord-307731-a2fqmaly.txt txt: ./txt/cord-307731-a2fqmaly.txt summary: In particular, the compounds obtained in the final rank order lead to meaningful increases in both performance and robustness over the single-modality approaches, but the results also demonstrate the sensitivity of the performance to the target structural details (i.e., the nature of the template ligand in measurements of molecular similarity and the reference protein pocket in docking studies) [67, 68] . In particular, the compounds obtained in the final rank order lead to meaningful increases in both performance and robustness over the single-modality approaches, but the results also demonstrate the sensitivity of the performance to the target structural details (i.e., the nature of the template ligand in measurements of molecular similarity and the reference protein pocket in docking studies) [67, 68] . abstract: Virtual screening (VS) is an outstanding cornerstone in the drug discovery pipeline. A variety of computational approaches, which are generally classified as ligand-based (LB) and structure-based (SB) techniques, exploit key structural and physicochemical properties of ligands and targets to enable the screening of virtual libraries in the search of active compounds. Though LB and SB methods have found widespread application in the discovery of novel drug-like candidates, their complementary natures have stimulated continued efforts toward the development of hybrid strategies that combine LB and SB techniques, integrating them in a holistic computational framework that exploits the available information of both ligand and target to enhance the success of drug discovery projects. In this review, we analyze the main strategies and concepts that have emerged in the last years for defining hybrid LB + SB computational schemes in VS studies. Particularly, attention is focused on the combination of molecular similarity and docking, illustrating them with selected applications taken from the literature. url: https://doi.org/10.3390/molecules25204723 doi: 10.3390/molecules25204723 id: cord-291086-goidlh08 author: Walker, Peter J. title: Rhabdovirus accessory genes date: 2011-09-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Rhabdoviridae is one of the most ecologically diverse families of RNA viruses with members infecting a wide range of organisms including placental mammals, marsupials, birds, reptiles, fish, insects and plants. The availability of complete nucleotide sequences for an increasing number of rhabdoviruses has revealed that their ecological diversity is reflected in the diversity and complexity of their genomes. The five canonical rhabdovirus structural protein genes (N, P, M, G and L) that are shared by all rhabdoviruses are overprinted, overlapped and interspersed with a multitude of novel and diverse accessory genes. Although not essential for replication in cell culture, several of these genes have been shown to have roles associated with pathogenesis and apoptosis in animals, and cell-to-cell movement in plants. Others appear to be secreted or have the characteristics of membrane-anchored glycoproteins or viroporins. However, most encode proteins of unknown function that are unrelated to any other known proteins. Understanding the roles of these accessory genes and the strategies by which rhabdoviruses use them to engage, divert and re-direct cellular processes will not only present opportunities to develop new anti-viral therapies but may also reveal aspects of cellar function that have broader significance in biology, agriculture and medicine. url: https://www.ncbi.nlm.nih.gov/pubmed/21933691/ doi: 10.1016/j.virusres.2011.09.004 id: cord-021626-ck2kybtp author: Walker-Smith, John title: Dietary protein intolerance date: 2013-10-21 words: 13881.0 sentences: 727.0 pages: flesch: 50.0 cache: ./cache/cord-021626-ck2kybtp.txt txt: ./txt/cord-021626-ck2kybtp.txt summary: Abnormalities of the small intestinal mucosa have been reported in children suffering temporary intolerances to cows'' milk protein, soy protein, gluten, eggs, chicken, ground rice and fish. The involvement of IgE in the immunological response of the lamina propria to milk challenge in children with cows'' milk protein intolerance has been described by Shiner and her colleagues (1975) , also by Kilby, Walker-Smith and Wood (1976) , who showed an increase in IgE cell numbers in the small intestinal mucosa after a milk challenge in a child with cows'' milk sensitive enteropathy. One remarkable exception is the case report of Watt, Pincott and Harries in 1983 of a child with coeliac disease whose small intestinal mucosa was responsive to cows'' milk until at least the age of 7 years. In addition to the above challenge procedure, related to small intestinal biopsy, various laboratory tests have been studied to help to diagnose cows'' milk protein intolerance. abstract: This chapter discusses dietary protein intolerance. Clinical food intolerance has many causes and many manifestations, including psychological aversion to the sight, smell, or taste of food as well as psychological intolerance to one or more of the many constituents of food. Dietary protein intolerance is the clinical syndrome resulting from the sensitization of an individual to one or more proteins that have been absorbed via a permeable mucosa in the small intestine. Intolerance to various food proteins, especially to cows' milk, has been recognized in children for many years. Such food intolerance may be the result of a variety of causes—for example, a congenital digestive enzyme defect such as sucrase–isomaltase deficiency or an acquired lactase deficiency secondary to small-intestinal mucosal damage, which in turn can be the result of a food allergy. The incidence of gastrointestinal food allergy diseases is greatest in the first few months and years of an infant's life and decreases with age. The acute syndrome is usually characterized by the sudden onset of vomiting, after cows' milk ingestion, occasionally followed by pallor and a shock-like state; however, acute anaphylaxis is rare. Acute abdominal pain seems to be a particular feature of fish hypersensitivity, while peanuts often produce immediate reactions in the oral mucosa as well as abdominal pain. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151781/ doi: 10.1016/b978-0-407-01320-9.50011-x id: cord-347710-ff64y6ef author: Wan, Qianya title: Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date: 2020-07-13 words: 36567.0 sentences: 2487.0 pages: flesch: 46.0 cache: ./cache/cord-347710-ff64y6ef.txt txt: ./txt/cord-347710-ff64y6ef.txt summary: hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. 6, 13 It is well known that Hsp90 not only interacts and contributes to RNA polymerase assembly and nuclear import of some (−) ssRNA viruses (e.g., PB2 of influenza virus), but plays crucial roles in the folding process of viral capsid proteins and virion assemblies as well. 17, 18 As a critical component of cellular protein surveillance, the ATP-dependent molecular chaperone protects cells from damage caused by stress and takes part in a number of folding processes, including folding of newly synthesized polypeptides, recognition and refolding of misfolded or aggregated proteins, solubilization or degradation of proteins, transporting proteins, assembly or disassembly of oligomeric protein complexes, and the regulation of certain natively folded proteins. abstract: Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II. hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. Dysregulation of stress proteins is associated with many human diseases including human cancer, cardiovascular diseases, neurodegenerative diseases (e.g., Parkinson’s diseases, Alzheimer disease), stroke and infectious diseases. In this review, we summarized the biologic function of stress proteins, and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections. As SPs also attract a great interest as potential antiviral targets (e.g., COVID-19), we also discuss the present progress and challenges in this area of HSP-based drug development, as well as with compounds already under clinical evaluation. url: https://www.ncbi.nlm.nih.gov/pubmed/32661235/ doi: 10.1038/s41392-020-00233-4 id: cord-299413-3o6mdx3e author: Wang, Hui title: Advantages of mRNA display selections over other selection techniques for investigation of protein–protein interactions date: 2014-01-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: mRNA display is a genotype–phenotype conjugation method that allows for amplification-based, iterative rounds of in vitro selection to be applied to peptides and proteins. mRNA display can be used to display both long natural protein and short synthetic peptide libraries with unusually high diversities for the investigation of protein–protein interactions. Here, we summarize the advantages of mRNA display by comparing it with other widely used peptide or protein-selection techniques, and discuss various applications of this technique in studying protein–protein interactions. url: https://doi.org/10.1586/epr.11.15 doi: 10.1586/epr.11.15 id: cord-354547-eomm1sl5 author: Wang, Jibin title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding date: 2009-03-16 words: 6319.0 sentences: 295.0 pages: flesch: 51.0 cache: ./cache/cord-354547-eomm1sl5.txt txt: ./txt/cord-354547-eomm1sl5.txt summary: title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding In this study, we report that interaction between coronavirus membrane protein (M) and actin with functional implication in facilitating virion assembly and budding. Similarly, analysis of cells expressing the M protein either on its own or together with the Myc-tagged actin by Western blot with anti-M polyclonal antibodies showed the detection of the full-length glycosylated (two upper bands) and unglycosylated (25 kDa) forms of the M protein (Fig. 2, lanes 5 and 6) . In cells transfected with both wild type and MD5 constructs with or without IBV infection, detection of similar amounts of M protein was observed (Fig. 5b, top two panels, lanes 1 and 2) , suggesting that both constructs were expressed at similar efficiencies. abstract: Coronavirus M protein is an essential component of virion and plays pivotal roles in virion assembly, budding and maturation. The M protein is integrated into the viral envelope with three transmembrane domains flanked by a short amino-terminal ectodomain and a large carboxy-terminal endodomain. In this study, we showed co-purification of the M protein from coronavirus infectious bronchitis virus (IBV) with actin. To understand the cellular factors that may be involved in virion assembly, budding and maturation processes, IBV M was used as the bait in a yeast two-hybrid screen, resulting in the identification of β-actin as a potentially interacting partner. This interaction was subsequently confirmed by coimmunoprecipitation and immunofluorescence microscopy in mammalian cells, and mutation of amino acids A159 and K160 on the M protein abolished the interaction. Introduction of the A159-K160 mutation into an infectious IBV clone system blocks the infectivity of the clone, although viral RNA replication and subgenomic mRNA transcription were actively detected. Disruption of actin filaments with cell-permeable agent cytochalasin D at early stages of the infection cycle led to the detection of viral protein synthesis in infected cells but not release of virus particles to the cultured media. However, the same treatment at late stages of the infection cycle did not affect the release of virus particles to the media, suggesting that disruption of the actin filaments might block virion assembly and budding, but not release of the virus particles. This study reveals an essential function of actin in the replication cycle of coronavirus. url: https://doi.org/10.1371/journal.pone.0004908 doi: 10.1371/journal.pone.0004908 id: cord-262268-gm99cadh author: Wang, Jingqiang title: Assessment of Immunoreactive Synthetic Peptides from the Structural Proteins of Severe Acute Respiratory Syndrome Coronavirus date: 2003-12-01 words: 4027.0 sentences: 189.0 pages: flesch: 49.0 cache: ./cache/cord-262268-gm99cadh.txt txt: ./txt/cord-262268-gm99cadh.txt summary: Consequently, we thoroughly investigated the immunoreactivities with patient sera of a series of synthesized peptides from SARS-coronavirus structural proteins. Results: Four epitopic sites, S599, M137, N66, and N371-404, located in the SARS-coronavirus S, M, and N proteins, respectively, were detected by screening synthesized peptides. The peptides representing the COOH terminus of the N protein, in particular N371 and N385, had high absorbance/cutoff value ratios with the highest positive detection rate and the lowest hydrophobicity score among all of the synthesized peptides (Fig. 1C, and Fig. 3 in the online Data Supplement). The other 17 peptides reacted only slightly with the sera from SARS patients and gave low detection rates, suggesting that the regions of the S protein covered by these peptides have no epitopic site. The patient sera preincubated with 4 mg/L S599 or N385 gave a 25-30% lower response in the ELISA (data not shown), suggesting that the two peptides could compete with SARS coronavirus for binding to the antibodies in SARS serum. abstract: Background: The widespread threat of severe acute respiratory syndrome (SARS) to human life has spawned challenges to develop fast and accurate analytical methods for its early diagnosis and to create a safe antiviral vaccine for preventive use. Consequently, we thoroughly investigated the immunoreactivities with patient sera of a series of synthesized peptides from SARS-coronavirus structural proteins. Methods: We synthesized 41 peptides ranging in size from 16 to 25 amino acid residues of relatively high hydrophilicity. The immunoreactivities of the peptides with SARS patient sera were determined by ELISA. Results: Four epitopic sites, S599, M137, N66, and N371-404, located in the SARS-coronavirus S, M, and N proteins, respectively, were detected by screening synthesized peptides. Notably, N371 and N385, located at the COOH terminus of the N protein, inhibited binding of antibodies to SARS-coronavirus lysate and bound to antibodies in >94% of samples from SARS study patients. N385 had the highest affinity for forming peptide-antibody complexes with SARS serum. Conclusions: Five peptides from SARS structural proteins, especially two from the COOH terminus of the N protein, appear to be highly immunogenic and may be useful for serologic assays. The identification of these antigenic peptides contributes to the understanding of the immunogenicity and persistence of SARS coronavirus. url: https://www.ncbi.nlm.nih.gov/pubmed/14633869/ doi: 10.1373/clinchem.2003.023184 id: cord-003297-fewy8y4a author: Wang, Ming-Yang title: A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs date: 2018-09-18 words: 9154.0 sentences: 486.0 pages: flesch: 48.0 cache: ./cache/cord-003297-fewy8y4a.txt txt: ./txt/cord-003297-fewy8y4a.txt summary: A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds. To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions. The contour maps around aconitine alkaloids generated by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) were combined with the interactions between ligand substituents and amino acids obtained from docking results to gain insight on the relationship between the structure of aconitine alkaloids and their toxicity. Finally, we combined the ligand-based 3D-QSTR analysis with the structure-based molecular docking study to identify the necessary moiety related to the cardiotoxicity mechanism of the aconitine alkaloids (in Figure 10 ). abstract: A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds. For the prediction research, a Protein-Protein Interaction (PPI) network was built from the extraction of useful information about protein interactions connected with aconitine cardiotoxicity, based on nearly a decade of literature and the STRING database. The software Cytoscape and the PharmMapper server were utilized to screen for essential proteins in the constructed network. The Calcium-Calmodulin-Dependent Protein Kinase II alpha (CAMK2A) and gamma (CAMK2G) were identified as potential targets. To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions. The molecular dynamics simulation carried out here have demonstrated that aconitine alkaloids possess binding stability for the receptor CAMK2G. In conclusion, this comprehensive method will serve as a tool for following a structural modification of the aconitine alkaloids and lead to a better insight into the cardiotoxicity induced by the compounds that have similar structures to its derivatives. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225272/ doi: 10.3390/molecules23092385 id: cord-193489-u6ewlh16 author: Wang, Rui title: Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine date: 2020-04-29 words: 6066.0 sentences: 419.0 pages: flesch: 62.0 cache: ./cache/cord-193489-u6ewlh16.txt txt: ./txt/cord-193489-u6ewlh16.txt summary: Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. Genetic identification and characterization of the geographic distribution, intercontinental evolution, and global trends of SARS-CoV-2 is the most efficient approach for studying COVID-19 genomic epidemiology and offer the molecular foundation for region-specific SARS-CoV-2 vaccine design, drug discovery, and diagnostic development [10] . We use K-means methods to cluster SARS-CoV-2 mutations, which provides the updated molecular information for the region-specific design of vaccines, drugs, and diagnoses. Table 5 presents the statistics of single mutations on various SARS-CoV-2 proteins that occurred in the recorded genomes between January 5, 2020, and April 24, 2020. Specifically, nucleocapsid protein has both the highest number of mutations per residues of 0.56 and the highest h-index of 27, suggesting that it is the most non-conservative protein in SARS-CoV-2 genomes. abstract: Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. We introduce mutation ratio and mutation $h$-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively non-conservative. In particular, the nucleocapsid protein has more than half its genes changed in the past few months, signaling devastating impacts on the ongoing development of COVID-19 diagnosis, vaccines, and drugs. url: https://arxiv.org/pdf/2004.14114v1.pdf doi: nan id: cord-258784-9bdd9krr author: Wei, Chiming title: New technology and clinical applications of nanomedicine: Highlights of the second annual meeting of the American Academy of Nanomedicine (Part I) date: 2006-12-31 words: 5540.0 sentences: 241.0 pages: flesch: 33.0 cache: ./cache/cord-258784-9bdd9krr.txt txt: ./txt/cord-258784-9bdd9krr.txt summary: During the Presidential Lecture, Chiming Wei, MD, PhD, of Johns Hopkins University, summarized new published and unpublished findings and results in each nanomedicine research area, and also reviewed the new nanotechnologies and clinical applications in nanomedicine development. The significance of these investigations lies in the development of platform technologies including nanoscale molecular imaging, drug delivery, gene delivery, and diagnostic approaches. Dendrimer-based nanomedicine was developed for protein mimicry research, nanopharmaceuticals, diagnostic imaging with contrast agents, and targeted drug delivery in cancer cells. In Canada some of the important nanomedicine research areas include intelligent drug delivery systems; vaccine and gene delivery nanosystems; polymeric systems and devices; biochips; lab-on-achip; artificial cells; anti-cancer, immune-, neural-and musculoskeletal systems; nanoscale targeting; tissue and cellular engineering; novel biomaterials; and molecular imaging. For the junior YIA scientists, Jean-Christophe Rochet of Purdue University received first place for his work to develop nanoimaging-based approaches for detection and analysis of protein misfolding states. abstract: Abstract The Second Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the National Acadmy of Science Building in Washinton, DC, September 9–10, 2006. The program included two Nobel Prize Laureate Lectures, two Keynote Lectures, and 123 invited outstanding State-in-Art lectures presenting in 23 special concurrent symposia. In addition, there were 22 poster presentations in the meeting addressing different areas in nanomedicine research. All of the presenters at the meeting are outstanding investigators and researchers in the field. The Second Annual Meeting of the AANM was a great success. The meeting provides investigators from different world areas a forum and an opportunity for discussion. We believe that nanomedicine research will develop rapidly in the future. The AANM invites basic and clinical researchers from the world to join this exciting research. url: https://www.ncbi.nlm.nih.gov/pubmed/17292151/ doi: 10.1016/j.nano.2006.11.001 id: cord-287450-hydy874v author: Wendt, K Ulrich title: Structures and diseases date: 2008 words: 2768.0 sentences: 103.0 pages: flesch: 35.0 cache: ./cache/cord-287450-hydy874v.txt txt: ./txt/cord-287450-hydy874v.txt summary: In early September 2007, about 180 structural biologists and biochemists met in the picturesque town of Murnau, located near Staffelsee Lake in the Bavarian alpine upland, to reflect on these questions and discuss recent biostructural data on the molecular determinants of human diseases, including microbial and viral infections, protein misfolding diseases, cancer and metabolic disorders. Starting the session on viral diseases, Rolf Hilgenfeld (University of Lübeck) reviewed the work from his laboratory on proteases of RNA viruses, such as severe acute respiratory syndrome (SARS) coronavirus and coxsackievirus B3, and also highlighted recent structural data on falcipain-2 from Plasmodium falciparum, discussing implications for the design of active-site directed and allosteric inhibitors for these cysteine proteases 14 . Günter Fritz (University of Konstanz) presented the unpublished structure of the ligand binding domain of RAGE, a multiligand receptor for advanced glycation end products, S100 proteins, HMGB1 and amyloid-β, whose activation is key to numerous chronic diseases such as diabetes, inflammation, arteriosclerosis and neurodegeneration, making it a potential therapeutic target 32, 33 . abstract: Structural biology is making significant contributions toward an understanding of molecular constituents and mechanisms underlying human diseases at an atomic resolution, as discussed at the international Murnau Conference on Structural Biology of Disease Mechanisms held in September 2007 in Murnau, Germany. url: https://www.ncbi.nlm.nih.gov/pubmed/18250627/ doi: 10.1038/nsmb0208-117 id: cord-313694-p2sgaypq author: West, Christopher M. title: Current ideas on the significance of protein glycosylation date: 1986 words: 10897.0 sentences: 534.0 pages: flesch: 36.0 cache: ./cache/cord-313694-p2sgaypq.txt txt: ./txt/cord-313694-p2sgaypq.txt summary: The alternate view is that carbohydrate structures participate in numerous specific interactions with discrete protein receptors, and that these interactions lead to predictable modifications in the localization or activity of the glycoprotein. The notion of a ''non-specific'' role for carbohydrate has received perhaps its strongest support from studies on cells whose glycosylation processes have been globally altered by mutation or drugs. Consideration of the possible role of carbohydrate in other molecular associations with the plasma membrane will be considered below in sections on hormone-receptor interactions and cellsubstratum (e.g., extracellular matrix) and cell-cell adhesion. Considerable evidence has been adduced that various parasites such as viruses, bacteria, protozoa, etc., possess carbohydrate binding proteins which can interact with sugar structures on the surfaces of cells with which the parasites associate (167, 168, (116) (117) (118) (119) . In any case, antibodies and lectins may model potential receptors in cells which might specifically recognize carbohydrate-associated structures. abstract: Carbohydrate has been removed from a number of glycoproteins without major effect on the structure or enzyme activity of the protein. Thus carbohydrate has been suggested to underly a non-primary function for proteins, such as in relatively non-specific interactions with other carbohydrates or macromolecules, stabilization of protein conformation, or protection from proteolysis. This non-specific concept is consistent with both the general similarity in carbohydrate structure on very diverse glycoproteins and the frequent structural microheterogeneity of carbohydrate chains at given sites. The concept is supported in a general sense by the viability of cells whose glycosylation processes have been globally disrupted by mutation or pharmacological inhibitors. In contrast to the above observations, other studies have revealed the existence of specific, selective receptors for discrete oligosaccharide structures on glycoproteins which seem to be important for compartmentalization of the glycoprotein, or the positioning of cells on which the glycoprotein is concentrated. Sometimes multivalency in the carbohydrate-receptor interaction is crucial. There are additional possible roles for carbohydrate in the transduction of information upon binding to a receptor. The possibility of specific roles for carbohydrate is supported by the existence of numerous unique carbohydrate structures, many of which have been detected as glycoantigens by monoclonal antibodies, with unique distributions in developing and differentiated cells. This article attempts to summarize and rationalize the contradictory results. It appears that in general carbohydrate does in fact underlie only roles secondary to a protein's primary function. These secondary roles are simple non-specific ones of protection and stabilization, but often also satisfy the more sophisticated needs of spatial position control and compartmentalization in multicellular eukaryotic organisms. It is suggested that there are advantages, evolutionarily speaking, for the shared use of carbohydrate for non-specific roles and for specific roles primarily as luxury functions to be executed during the processes of cell differentiation and morphogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/3029560/ doi: 10.1007/bf00230632 id: cord-264031-0y7xbgun author: Wierbowski, Shayne D. title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date: 2020-10-13 words: 5066.0 sentences: 291.0 pages: flesch: 42.0 cache: ./cache/cord-264031-0y7xbgun.txt txt: ./txt/cord-264031-0y7xbgun.txt summary: title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. Further, we explore the utility of our interactome modeling approach in identifying key 99 interactions undergoing evolution along viral protein interfaces, highlighting population variants on 100 human interfaces that could modulate the strength of viral-host interactions to confer protection from or 101 susceptibility to COVID-19, and prioritizing drug candidates predicted to bind competitively at viral-102 human interaction interfaces. abstract: The recent COVID-19 pandemic has sparked a global public health crisis. Vital to the development of informed treatments for this disease is a comprehensive understanding of the molecular interactions involved in disease pathology. One lens through which we can better understand this pathology is through the network of protein-protein interactions between its viral agent, SARS-CoV-2, and its human host. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV can be explained by rapid evolution along the interface between the Spike protein and its human receptor (ACE2) leading to increased binding affinity. Sequence divergences that modulate other protein-protein interactions may further explain differences in transmission and virulence in this novel coronavirus. To facilitate these comparisons, we combined homology-based structural modeling with the ECLAIR pipeline for interface prediction at residue resolution, and molecular docking with PyRosetta. This enabled us to compile a novel 3D structural interactome meta-analysis for the published interactome network between SARS-CoV-2 and human. This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. All predictions are available online† for easy access and are continually updated when new interactions are published. † Some sections of this pre-print have been redacted to comply with current bioRxiv policy restricting the dissemination of purely in silico results predicting potential therapies for SARS-CoV-2 that have not undergone thorough peer-review. The results section titled “Prioritization of Candidate Inhibitors of SARS-CoV-2-Human Interactions Through Binding Site Comparison,” Figure 4, Supplemental Table 9, and all links to our web resource have been removed. Blank headers left in place to preserve structure and item numbering. Our full manuscript will be published in an appropriate journal following peer-review. url: https://doi.org/10.1101/2020.10.13.308676 doi: 10.1101/2020.10.13.308676 id: cord-306624-1mjmttec author: Wodrich, Harald title: A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry date: 2010-03-19 words: 11594.0 sentences: 666.0 pages: flesch: 53.0 cache: ./cache/cord-306624-1mjmttec.txt txt: ./txt/cord-306624-1mjmttec.txt summary: We show that the PPxY motif in protein VI is involved in its efficient microtubule-mediated transport and mutating it in the virus alters the intracellular targeting of Ads towards the MTOC region concomitant with a post-entry block in viral infectivity. To identify possible trafficking determinants, we analyzed the sequences of protein VI from several Ad serotypes and identified a highly conserved ubiquitin-ligase interacting motif present in PPxY-type viral late domains (PPxY, Figure S2 ). To determine whether the M1 mutation influences Ad cell entry, we performed a fluorescent focus forming assay and stained cells at 8, 12 and 24 h post-infection for expression of the E2A protein, which marks the appearance of viral replication centers ( Figure 2D and data not shown). In addition to the increase of protein VI capsid association, Ad5-VI-M1 appeared to be more evenly distributed throughout the cell and did not efficiently accumulate at the MTOC region ( Figure 3B , images to the left). abstract: Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated with the capsid during intracellular transport. We found that a PPxY motif within protein VI recruits Nedd4 E3 ubiquitin ligases to bind and ubiquitylate protein VI. We further show that this PPxY motif is involved in rapid, microtubule-dependent intracellular movement of protein VI. Ads with a mutated PPxY motif can efficiently escape endosomes but are defective in microtubule-dependent trafficking toward the nucleus. Likewise, depletion of Nedd4 ligases attenuates nuclear accumulation of incoming Ad particles and infection. Our data provide the first evidence that virus-encoded PPxY motifs are required during virus entry, which may be of significance for several other pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/20333243/ doi: 10.1371/journal.ppat.1000808 id: cord-103509-hynnba03 author: Wong, Ten-Tsao title: A self-assembled protein nanoparticle serving as a one-shot vaccine carrier date: 2020-09-18 words: 3187.0 sentences: 148.0 pages: flesch: 48.0 cache: ./cache/cord-103509-hynnba03.txt txt: ./txt/cord-103509-hynnba03.txt summary: From these two clues, it was hypothesized that AH3-GFP fusion protein form stable protein complex through hydrophobic interaction mediated by N-terminal AH3 peptide. Using the same protocol, AH3-GFP was found to co-sedimented with the bacterial membrane (Fig. S3A) as well as the AH3-sfGFP-hM2e fusion protein but not a free GFP protein (Fig S3B) These results are consistent with our protein structure modeling that Arg11 serves as a main contact point for dimer stacking also it mediates the electrostatic interaction with mutated Glu13 (Fig. 3E ). These results suggest that the two point mutations of AH3 in I8L and K13E enable the formation of a stable, high antigenic protein complex that stimulates long lasting immune responses in a single immunization. The result suggests that although carrier protein AH3-sfGFP also has high antigenicity, it did not interfere with the immune response against the heterologous protein, hM2e (Fig. 5B, 5C) abstract: In this paper, we are exploring the role of an amphipathic helical peptide in mediating the self-assembly of a fusion protein into a protein nanoparticle and the application of the nanoparticle as a one-shot vaccine carrier. Out of several candidates, an amphipathic helical peptide derived from M2 protein of type A influenza virus is found to stimulate high antigenicity when fused to a fluorescent protein genetically. This fusion protein was found to form protein nanoparticle spontaneously when expressed and purified protein stimulates long-lasting antibody responses in single immunization. Through modeling peptide structure and nanoparticle assembly, we have improved this vaccine carrier in complex stability. The revised vaccine carrier is able to stimulate constant antibody titer to a heterologous antigen for at least six months in single immunization. The immune response against a heterologous antigen can be boosted further by additional immunization in spite of high immune responses to carrier protein. url: https://doi.org/10.1101/2020.09.16.299149 doi: 10.1101/2020.09.16.299149 id: cord-252576-1ec545o2 author: Wu, Xiangli title: An antifungal defensin from Phaseolus vulgaris cv. ‘Cloud Bean’ date: 2011-01-15 words: 3562.0 sentences: 195.0 pages: flesch: 55.0 cache: ./cache/cord-252576-1ec545o2.txt txt: ./txt/cord-252576-1ec545o2.txt summary: An antifungal peptide with a defensin-like sequence and exhibiting a molecular mass of 7.3 kDa was purified from dried seeds of Phaseolus vulgaris ''Cloud Bean''. After elution of unadsorbed proteins (fraction S1), adsorbed proteins were desorbed with a linear concentration (0-1 M) gradient of NaCl. The fraction with antifungal activity (S2) was then further fractionated by fast protein liquid chromatography on a Superdex 75 HR 10/30 column (GE Healthcare) in 0.2 M NH 4 HCO 3 buffer (pH 8.5). Antiproliferative activity toward tumor cells is also an attribute of defensins (Wong and Ng 2003) , defensin-like peptides and also other antifungal proteins including ribosome inactivating proteins (Lam et al. Some antifungal proteins including defensin-like peptides (Wong and Ng 2003) , protease inhibitors (Ye et al. The present findings on cloud bean defensin is reminiscent of the observation that mungin, an antifungal protein from mung beans, is without HIV-1 reverse transcriptase inhibitory activity (Ye and Ng 2000) . Concurrent purification of two defense proteins from French bean seeds: a defensin-like antifungal peptide and a hemagglutinin abstract: An antifungal peptide with a defensin-like sequence and exhibiting a molecular mass of 7.3 kDa was purified from dried seeds of Phaseolus vulgaris ‘Cloud Bean’. The isolation procedure entailed anion exchange chromatography on DEAE-cellulose, affinity chromatography an Affi-gel blue gel, cation exchange chromatography on SP-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. Although the antifungal peptide was unadsorbed on DEAE-cellulose, it was adsorbed on both Affi-gel blue gel and SP-Sepharose. The antifungal peptide exerted antifungal activity against Mycosphaerella arachidicola with an IC(50) value of 1.8 μM. It was also active against Fusarium oxysporum with an IC(50) value of 2.2 μM. It had no inhibitory effect on HIV-1 reverse transcriptase when tested up to 100 μM. Proliferation of L1210 mouse leukemia cells and MBL2 lymphoma cells was inhibited by the antifungal peptide with an IC(50) of 10 μM and 40 μM, respectively. url: https://www.sciencedirect.com/science/article/pii/S0944711310001923 doi: 10.1016/j.phymed.2010.06.010 id: cord-340387-ohkjheat author: Wynne, James W. title: Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA date: 2013-01-07 words: 7004.0 sentences: 390.0 pages: flesch: 52.0 cache: ./cache/cord-340387-ohkjheat.txt txt: ./txt/cord-340387-ohkjheat.txt summary: title: Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. Considering that in other mammalian species, immunoglobulins IgG, IgM and IgA are present in relatively high abundance in serum and tissues, we anticipated that bats would possess a similar immunoglobulin profile. IgG-depleted samples were fractionated by affinity chromatography on immobilised anti-Fab-specific antibodies adopting the same procedure as that described for immobilised Protein A and G except that the binding and washing buffer consisted of 0.3 M NaCl in 50 mM phosphate buffer, pH 7.4. Two major bands were detected by reducing SDS-PAGE in the eluate from both serum and plasma samples; a 66-70 kDa band representative of IgM H , and a 25 kDa band representative of immunoglobulin light chain ( Fig. 3A and 3B ). abstract: There is now an overwhelming body of evidence that implicates bats in the dissemination of a long list of emerging and re-emerging viral agents, often causing illnesses or death in both animals and humans. Despite this, there is a paucity of information regarding the immunological mechanisms by which bats coexist with highly pathogenic viruses. Immunoglobulins are major components of the adaptive immune system. Early studies found bats may have quantitatively lower antibody responses to model antigens compared to conventional laboratory animals. To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. We employed a novel strategy, where IgG was initially purified and used to generate anti-Fab specific antibodies. Immobilised anti-Fab specific antibodies were then used to capture other immunoglobulins from IgG depleted serum. While high quantities of IgM were successfully isolated from serum, IgA was not. Only trace quantities of IgA were detected in the serum by mass spectrometry. Immobilised ligands specific to IgA (Jacalin, Peptide M and staphylococcal superantigen-like protein) also failed to capture P. alecto IgA from serum. IgM was the second most abundant serum antibody after IgG. A survey of mucosal secretions found IgG was the dominant antibody class rather than IgA. Our study demonstrates healthy P. alecto bats have markedly less serum IgA than expected. Higher quantities of IgG in mucosal secretions may be compensation for this low abundance or lack of IgA. Knowledge and reagents developed within this study can be used in the future to examine class-specific antibody response within this important viral host. url: https://www.ncbi.nlm.nih.gov/pubmed/23308125/ doi: 10.1371/journal.pone.0052930 id: cord-274393-1geyuxtk author: Xie, Wenyan title: Mutations in the Leucine Zipper-Like Motif of the Human Parainfluenza Virus 3 Fusion Protein Impair Fusion Activity date: 2015-12-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: OBJECTIVE: To investigate the effect of the leucine zipper-like motif between HRA and HRB of the human parainfluenza virus 3 fusion protein on fusion activity. METHODS: Site-directed mutagenesis was utilized to substitute the heptadic residues at 257, 264, 271, 278, 285, 292, and 299 in this motif with alanine. Additionally, 3 middle heptadic leucine residues at 271, 278, and 285 were replaced with alanine singly or in combination. A vaccinia virus-T7 RNA polymerase transient expression system was employed to express the wild-type or mutated fusion (F) proteins. Three different types of membrane fusion assays were performed to analyze the fusogenic activity, fluorescence-activated cell sorting (FACS) analysis was executed to examine the cell surface expression level, and a coimmunoprecipitation assay was conducted to probe the hemagglutinin-neuraminidase (HN)-F interaction at the cell surface. RESULTS: All of the substitutions in this motif exhibited diminished or even lost fusion activity in all stages of fusion, although they all had no effect on cell surface expression. In the coimmunoprecipitation assay, all mutants resulted in decreased detection of the HN-F complexes compared with that of the wild-type F protein. CONCLUSIONS: This motif has an important influence on fusion activity, and its integrality is indispensable for membrane fusion. url: https://doi.org/10.1159/000441978 doi: 10.1159/000441978 id: cord-000575-g1ob16b9 author: Xie, Xiao-li title: Protein sequence analysis based on hydropathy profile of amino acids date: 2012-01-27 words: 2178.0 sentences: 116.0 pages: flesch: 48.0 cache: ./cache/cord-000575-g1ob16b9.txt txt: ./txt/cord-000575-g1ob16b9.txt summary: A new method to analyze the similarity/dissimilarity of protein sequence was proposed based on the conditional probability of the protein sequence. Based on the graphical representation, it is possible to numerically characterize DNA sequence and further quantitatively measure similarity of different DNA sequences. This is mainly because extension of DNA graphical representation to protein sequences would enormously increase the number of possible alternative assignments for the 20 amino acids. The graphical representation of protein sequence cannot only describe amino acid sequence, but also measure similarity/ dissimilarity of different protein sequences. In this paper, we converted a protein sequence into three-letter sequence based on hydropathy profile of amino acid and defined the three curves to represent different hydropathy features. The method is based on the graphical representation and conditional probability taken as the numerical characterization of the protein sequence. Similarity/dissimilarity studies of protein sequences based on a new 2D graphical representation abstract: Biology sequence comparison is a fundamental task in computational biology. According to the hydropathy profile of amino acids, a protein sequence is taken as a string with three letters. Three curves of the new protein sequence were defined to describe the protein sequence. A new method to analyze the similarity/dissimilarity of protein sequence was proposed based on the conditional probability of the protein sequence. Finally, the protein sequences of ND6 (NADH dehydrogenase subunit 6) protein of eight species were taken as an example to illustrate the new approach. The results demonstrated that the method is convenient and efficient. url: http://europepmc.org/articles/pmc3274743?pdf=render doi: 10.1631/jzus.b1100052 id: cord-328046-5us4se5o author: Xu, H. Y. title: Further Identification and Characterization of Novel Intermediate and Mature Cleavage Products Released from the ORF 1b Region of the Avian Coronavirus Infectious Bronchitis Virus 1a/1b Polyprotein date: 2001-09-30 words: 5643.0 sentences: 279.0 pages: flesch: 51.0 cache: ./cache/cord-328046-5us4se5o.txt txt: ./txt/cord-328046-5us4se5o.txt summary: In cells infected with avian coronavirus infectious bronchitis virus (IBV), three proteins of 100, 39, and 35 kDa, respectively, were previously identified as mature cleavage products released from the 1b region of the 1a/1b polyprotein by the 3C-like proteinase. Immunofluorescent staining of IBV-infected cells and cells expressing individual cleavage products showed that the 100-, 68-, and 58-kDa proteins were associated with the membranes of the endoplasmic reticulum, and the 39and 35-kDa proteins displayed diffuse distribution patterns. Taken together with the Q 3928 -S 2929 dipeptide bond (encoded by nucleotides 12310-12315) identified as the N-terminal cleavage site of the 100-kDa protein, cleavage at these positions would result in the release of five mature products with molecular masses of approximately 100, 68, 58, 39, and 35 kDa. Among them, the 100-, 39-, and 35-kDa proteins were specifically identified in IBV-infected cells (Liu et al., 1994 . abstract: Abstract The coronavirus 3C-like proteinase is one of the viral proteinases responsible for processing of the 1a and 1a/1b polyproteins to multiple mature products. In cells infected with avian coronavirus infectious bronchitis virus (IBV), three proteins of 100, 39, and 35 kDa, respectively, were previously identified as mature cleavage products released from the 1b region of the 1a/1b polyprotein by the 3C-like proteinase. In this report, we show the identification of two more cleavage products of 68 and 58 kDa released from the same region of the polyprotein. In addition, two stable intermediate cleavage products with molecular masses of 160 and 132 kDa, respectively, were identified in IBV-infected cells. The 160-kDa protein was shown to be an intermediate cleavage product covering the 100- and 68-kDa proteins, and the 132-kDa protein to be an intermediate cleavage product covering the 58-, 39-, and 35-kDa proteins. Immunofluorescent staining of IBV-infected cells and cells expressing individual cleavage products showed that the 100-, 68-, and 58-kDa proteins were associated with the membranes of the endoplasmic reticulum, and the 39- and 35-kDa proteins displayed diffuse distribution patterns. url: https://api.elsevier.com/content/article/pii/S0042682201910980 doi: 10.1006/viro.2001.1098 id: cord-018963-2lia97db author: Xu, Ying title: Protein Structure Prediction by Protein Threading date: 2010-04-29 words: 15309.0 sentences: 716.0 pages: flesch: 48.0 cache: ./cache/cord-018963-2lia97db.txt txt: ./txt/cord-018963-2lia97db.txt summary: Their follow-up work (Elofsson et aI., 1996; Fischer and Eisenberg, 1996; Fischer et aI., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et aI., 1992) on protein fold recognition led to the development of a new brand ofpowerful tools for protein structure prediction, which we now term "protein threading." These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many ofthe proteins encoded in the hundreds of genomes that have been sequenced up to now. abstract: The seminal work of Bowie, Lüthy, and Eisenberg (Bowie et al., 1991) on “the inverse protein folding problem” laid the foundation of protein structure prediction by protein threading. By using simple measures for fitness of different amino acid types to local structural environments defined in terms of solvent accessibility and protein secondary structure, the authors derived a simple and yet profoundly novel approach to assessing if a protein sequence fits well with a given protein structural fold. Their follow-up work (Elofsson et al., 1996; Fischer and Eisenberg, 1996; Fischer et al., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et al., 1992) on protein fold recognition led to the development of a new brand of powerful tools for protein structure prediction, which we now term “protein threading.” These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many of the proteins encoded in the hundreds of genomes that have been sequenced up to now. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123984/ doi: 10.1007/978-0-387-68825-1_1 id: cord-262748-v4xue7ha author: Xu, Yongtao title: Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine date: 2015-12-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The peptides derived from envelope proteins have been shown to inhibit the protein-protein interactions in the virus membrane fusion process and thus have a great potential to be developed into effective antiviral therapies. There are three types of envelope proteins each exhibiting distinct structure folds. Although the exact fusion mechanism remains elusive, it was suggested that the three classes of viral fusion proteins share a similar mechanism of membrane fusion. The common mechanism of action makes it possible to correlate the properties of self-derived peptide inhibitors with their activities. Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The model displayed 92% prediction accuracy with the Matthew’s correlation coefficient of 0.84, obviously superior to those using physicochemical properties and amino acid decomposition as input. The predictive support vector machine model for self- derived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process. url: https://www.ncbi.nlm.nih.gov/pubmed/26636321/ doi: 10.1371/journal.pone.0144171 id: cord-286635-7aflpgxd author: YANG, Yong-xin title: Comparative Proteomic Analysis of Plasma from Clinical Healthy Cows and Mastitic Cows date: 2009-10-31 words: 2471.0 sentences: 102.0 pages: flesch: 47.0 cache: ./cache/cord-286635-7aflpgxd.txt txt: ./txt/cord-286635-7aflpgxd.txt summary: After staining with silver nitrate and Coomassie Blue, differential expression proteins were detected by PDQuest 7.4 software, and then subjected to ion trap mass spectrometer equipped with a Surveyor HPLC System, differential spots of protein were identified. This investigation was to detect the expressed proteins in plasma from clinical mastitic and healthy dairy cows by 2-DE providing a platform for parallel analysis, and then, to identify differential proteins by ion trap mass spectrometer equipped with HPLC System, in order to probe the pathogenesis of mastitis and find new biomarkers of mastitis-associated proteins for diagnosis and treatment. To probe protein expression pattern changes in plasma from healthy dairy cows and clinical mastitic cows, this subject analyzed and identified differential protein spots using 2-DE and ion trap mass spectrometer equipped with HPLC System. abstract: Abstract The current research presents the protein changes in plasma from healthy dairy cows and clinical mastitic cows using two-dimensional gel electrophoresis (2-DE). After staining with silver nitrate and Coomassie Blue, differential expression proteins were detected by PDQuest 7.4 software, and then subjected to ion trap mass spectrometer equipped with a Surveyor HPLC System, differential spots of protein were identified. Three protein spots that originated from preparation gels were identified to be two proteins. Overall, haptoglobin precursor was up-regulated in cows infected with clinical mastitis and could be a mastitis-associated diagnostic marker, whereas SCGB 2A1 (secretoglobin, family 2A, member 1) was down-regulated protein. Plasma protein expression patterns were changed when cows were infected with mammary gland inflammation; it suggests that analysis of differential expression protein might be useful to clarify the mechanisms involved in the pathophysiology, and find new diagnostic markers of mastitis and potential protein targets for treatment. url: https://api.elsevier.com/content/article/pii/S1671292708603375 doi: 10.1016/s1671-2927(08)60337-5 id: cord-274293-kzmch37j author: Yang, Li title: Tandem mass tag-based quantitative proteomic analysis of lycorine treatment in highly pathogenic avian influenza H5N1 virus infection date: 2019-10-02 words: 6734.0 sentences: 347.0 pages: flesch: 46.0 cache: ./cache/cord-274293-kzmch37j.txt txt: ./txt/cord-274293-kzmch37j.txt summary: Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Therefore, we performed a comparative proteomic analysis to determine the effects of lycorine at the protein level in GD178-infected MDCK cells to understand its mode of action. The functional classification of DEPs was conducted by KEGG enrichment analysis, and each protein was assigned to at least one of the following pathways: human T-lymphotropic virus-1 infection pathway (path: ko05166), cell adhesion molecules (CAMs) (path: ko04514), epidermal growth factor receptor tyrosine kinase inhibitor resistance (path: ko01521), Janus kinase-STAT signaling pathway (path: ko04630), and pancreatic cancer (path: ko05212) (Fig. 3C) . As a result, AIV infection may induce Nup93 to complete the viral cycle, and the process of protein targeting into Nup93 after lycorine treatment may partly be explained by the blockage of vRNPs in the host cellular nucleus. Functional proteomic studies of lycorine-treated MDCK cells on highly pathogenic avian influenza H5N1 virus infection abstract: Highly pathogenic H5N1 influenza viruses (HPAIV) cause rapid systemic illness and death in susceptible animals, leading to a disease with high morbidity and mortality rates. Although vaccines and drugs are the best solution to prevent this threat, a more effective treatment for H5 strains of influenza has yet to be developed. Therefore, the development of therapeutics/drugs that combat H5N1 influenza virus infection is becoming increasingly important. Lycorine, the major component of Amaryllidaceae alkaloids, exhibits better protective effects against A/CK/GD/178/04 (H5N1) (GD178) viruses than the commercial neuraminidase (NA) inhibitor oseltamivir in our prior study. Lycorine demonstrates outstanding antiviral activity because of its inhibitory activity against the export of viral ribonucleoprotein complexes (vRNPs) from the nucleus. However, how lycorine affects the proteome of AIV infected cells is unknown. Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Three groups were designed: mock infection group (M), virus infection group (V), and virus infection and lycorine-treated after virus infection group (L). The multiplexed tandem mass tag (TMT) approach was employed to analyze protein level in this study. In total, 5,786 proteins were identified from the three groups of cells by using TMT proteomic analysis. In the V/M group, 1,101 proteins were identified, of which 340 differentially expressed proteins (DEPs) were determined during HPAIV infection; among the 1,059 proteins identified from the lycorine-treated group, 258 proteins presented significant change. Here, 71 proteins showed significant upregulation or downregulation of expression in the virus-infected/mock and virus-infected/lycorine-treated comparisons, and the proteins in each fraction were functionally classified further. Interestingly, lycorine treatment decreased the levels of the nuclear pore complex protein 93 (Nup93, E2RSV7), which is associated with nuclear–cytoplasmic transport. In addition, Western blot experiments confirmed that the expression of Nup93 was significantly downregulated in lycorine treatment but induced after viral infection. Our results may provide new insights into how lycorine may trap vRNPs in the nucleus and suggest new potential therapeutic targets for influenza virus. url: https://www.ncbi.nlm.nih.gov/pubmed/31592345/ doi: 10.7717/peerj.7697 id: cord-321441-t1v0pu0w author: Yang, Yiming title: Polycistronic Genome Segment Evolution and Gain and Loss of FAST Protein Function during Fusogenic Orthoreovirus Speciation date: 2020-06-29 words: 8639.0 sentences: 363.0 pages: flesch: 41.0 cache: ./cache/cord-321441-t1v0pu0w.txt txt: ./txt/cord-321441-t1v0pu0w.txt summary: New phylogenetic analyses that included the atypical waterfowl subgroup of avian reoviruses and recently identified new orthoreovirus species indicate a more complex relationship between reovirus speciation and fusogenic capacity, with numerous predicted internal indels and 5''-terminal extensions driving the evolution of the orthoreovirus'' polycistronic genome segments and their encoded FAST and fiber proteins. We further show that two distinct post-speciation genetic events led to the loss of fusion in the waterfowl isolates of avian reovirus, a recombination event that replaced the p10 FAST protein with a heterologous, non-fusogenic protein and point substitutions in a conserved motif that destroyed the p10 assembly into multimeric fusion platforms. MdRVs are divided into two subgroups, the "classical" and "novel" MdRVs. Classical Muscovy duck reoviruses (MdRVc) possess a bicistronic S4 genome segment encoding a truncated fiber protein of 269 residues and a p11 protein that lacks sequence similarity to the p10 FAST proteins of ARV, ARVN, and NBV ( Figure 1B ) [50] . abstract: The Reoviridae family is the only non-enveloped virus family with members that use syncytium formation to promote cell–cell virus transmission. Syncytiogenesis is mediated by a fusion-associated small transmembrane (FAST) protein, a novel family of viral membrane fusion proteins. Previous evidence suggested the fusogenic reoviruses arose from an ancestral non-fusogenic virus, with the preponderance of fusogenic species suggesting positive evolutionary pressure to acquire and maintain the fusion phenotype. New phylogenetic analyses that included the atypical waterfowl subgroup of avian reoviruses and recently identified new orthoreovirus species indicate a more complex relationship between reovirus speciation and fusogenic capacity, with numerous predicted internal indels and 5’-terminal extensions driving the evolution of the orthoreovirus’ polycistronic genome segments and their encoded FAST and fiber proteins. These inferred recombination events generated bi- and tricistronic genome segments with diverse gene constellations, they occurred pre- and post-orthoreovirus speciation, and they directly contributed to the evolution of the four extant orthoreovirus FAST proteins by driving both the gain and loss of fusion capability. We further show that two distinct post-speciation genetic events led to the loss of fusion in the waterfowl isolates of avian reovirus, a recombination event that replaced the p10 FAST protein with a heterologous, non-fusogenic protein and point substitutions in a conserved motif that destroyed the p10 assembly into multimeric fusion platforms. url: https://doi.org/10.3390/v12070702 doi: 10.3390/v12070702 id: cord-275124-7l53bvp1 author: Yao, Minghui title: A potential treatment for COVID-19 based on modal characteristics and dynamic responses analysis of 2019-nCoV date: 2020-10-21 words: 2489.0 sentences: 170.0 pages: flesch: 64.0 cache: ./cache/cord-275124-7l53bvp1.txt txt: ./txt/cord-275124-7l53bvp1.txt summary: The finite element analysis (FEA) is used to study the modal characteristics of the tuned 2019-nCoV model and mistuned 2019-nCoV model in blood, respectively. Because of the relatively heavy mass of the sphere body compared to spike proteins, its modes are rigid body motion, which the sphere of COVID-19 model is fixed in modal analysis. Based on the first-order bending vibration form, the lumped mechanical model is established as illustrated in Fig. 5 . The harmonic response is conducted after the modal analysis of the mistuned 2019-nCoV model, and acceleration excitation is set as 1 mm/s 2 , as shown in Fig. 6 . (1) The frequencies of the tuned 2019-nCoV model are very close to each other, and they are all first-order bending vibrations. The frequencies of the realistic mistuned 2019-nCoV model are a range of frequencies close to each other, and every frequency corresponds to the first-order bending vibration of one spike protein. abstract: The 2019-nCoV is ravaging the world, taking lots of lives, and it is emergent to find a solution to deal with this novel pneumonia. This paper provides a potential treatment for COVID-19 utilizing resonance to destroy the infection ability of 2019-nCoV. Firstly, the geometry size of 2019-nCoV is scaled up by 10,000 times. The additional mass is used to represent the effect of the fluid around a spike protein. The finite element analysis (FEA) is used to study the modal characteristics of the tuned 2019-nCoV model and mistuned 2019-nCoV model in blood, respectively. Based on FEA, the lumped parameter mechanical model of 2019-nCoV is established. Then, the dynamic responses of mistuned 2019-nCoV are investigated through harmonic response and dynamical analysis. Finally, a potential method utilizing 360° sweep excitation to cure COVID-19 is put forward. url: https://www.ncbi.nlm.nih.gov/pubmed/33106729/ doi: 10.1007/s11071-020-06019-1 id: cord-261472-qcu73sdu author: Yao, Yong Xiu title: Cleavage and Serum Reactivity of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein date: 2004-07-01 words: 3851.0 sentences: 159.0 pages: flesch: 47.0 cache: ./cache/cord-261472-qcu73sdu.txt txt: ./txt/cord-261472-qcu73sdu.txt summary: Severe acute respiratory syndrome (SARS) coronavirus (SCoV) spike (S) protein is the major surface antigen of the virus and is responsible for receptor binding and the generation of neutralizing antibody. To investigate SCoV S protein, full-length and individual domains of S protein were expressed on the surface of insect cells and were characterized for cleavability and reactivity with serum samples obtained from patients during the convalescent phase of SARS. The possible use of insect cell-displayed S protein for diagnostic application was assessed by examining fragment reactivity with serum samples from patients infected with human CoV 229E and also with serum from a patient with suspected but clinically unconfirmed SARS (serum sample 3118). Of the 2 assay formats we used, nondenatured S protein present on the cell surface provided the most sensitive detection of antibodies, with clear shifts in fluorescence for serum samples from patients with suspected but clinically unconfirmed SARS. abstract: Severe acute respiratory syndrome (SARS) coronavirus (SCoV) spike (S) protein is the major surface antigen of the virus and is responsible for receptor binding and the generation of neutralizing antibody. To investigate SCoV S protein, full-length and individual domains of S protein were expressed on the surface of insect cells and were characterized for cleavability and reactivity with serum samples obtained from patients during the convalescent phase of SARS. S protein could be cleaved by exogenous trypsin but not by coexpressed furin, suggesting that the protein is not normally processed during infection. Reactivity was evident by both flow cytometry and Western blot assays, but the pattern of reactivity varied according to assay and sequence of the antigen. The antibody response to SCoV S protein involves antibodies to both linear and conformational epitopes, with linear epitopes associated with the carboxyl domain and conformational epitopes associated with the amino terminal domain. Recombinant SCoV S protein appears to be a suitable antigen for the development of an efficient and sensitive diagnostic test for SARS, but our data suggest that assay format and choice of S antigen are important considerations. url: https://www.ncbi.nlm.nih.gov/pubmed/15195247/ doi: 10.1086/421280 id: cord-253844-y6xdcf20 author: Yesudhas, Dhanusha title: COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics date: 2020-09-04 words: 7165.0 sentences: 422.0 pages: flesch: 51.0 cache: ./cache/cord-253844-y6xdcf20.txt txt: ./txt/cord-253844-y6xdcf20.txt summary: In SARS-CoV-2 infection, intrinsically disordered regions are observed at the interface of the spike protein and ACE2 receptor, providing a shape complementarity to the complex. SUMMARY: The overall history and mechanism of entry of SARS-CoV-2 along with structural study of spike-ACE2 complex provide insights to understand disease pathogenesis and development of vaccines and drugs. The sequence similarity between SARS-CoV-2 and SARS-CoV spike proteins explains the possibility of binding to the same receptor angiotensin converting enzyme 2 (ACE2) in the host cell [14] . In this review, we discuss the history of coronaviruses in both humans and animals, their transmissions, mechanism of host cell entry and the structural studies, explaining active and inactive receptor binding of spike protein and the key residues playing an important role in the receptor binding. During viral infection, spike protein (~ 1300 amino acid residues) is cleaved by host proteases into receptor binding subunit S1 and membrane fusion subunit S2. abstract: PURPOSE: The coronavirus outbreak emerged as a severe pandemic, claiming more than 0.8 million lives across the world and raised a major global health concern. We survey the history and mechanism of coronaviruses, and the structural characteristics of the spike protein and its key residues responsible for human transmissions. METHODS: We have carried out a systematic review to summarize the origin, transmission and etiology of COVID-19. The structural analysis of the spike protein and its disordered residues explains the mechanism of the viral transmission. A meta-data analysis of the therapeutic compounds targeting the SARS-CoV-2 is also included. RESULTS: Coronaviruses can cross the species barrier and infect humans with unexpected consequences for public health. The transmission rate of SARS-CoV-2 infection is higher compared to that of the closely related SARS-CoV infections. In SARS-CoV-2 infection, intrinsically disordered regions are observed at the interface of the spike protein and ACE2 receptor, providing a shape complementarity to the complex. The key residues of the spike protein have stronger binding affinity with ACE2. These can be probable reasons for the higher transmission rate of SARS-CoV-2. In addition, we have also discussed the therapeutic compounds and the vaccines to target SARS-CoV-2, which can help researchers to develop effective drugs/vaccines for COVID-19. SUMMARY: The overall history and mechanism of entry of SARS-CoV-2 along with structural study of spike-ACE2 complex provide insights to understand disease pathogenesis and development of vaccines and drugs. url: https://doi.org/10.1007/s15010-020-01516-2 doi: 10.1007/s15010-020-01516-2 id: cord-329625-hx2rsi91 author: You, Jae-Hwan title: A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging date: 2008-08-15 words: 5645.0 sentences: 271.0 pages: flesch: 46.0 cache: ./cache/cord-329625-hx2rsi91.txt txt: ./txt/cord-329625-hx2rsi91.txt summary: title: A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. To investigate whether the trafficking of N protein between the cytoplasm and the nucleus/nucleolus was associated with microtubules or energy dependent, the mobility of EGFP-PRRSV-N protein was compared in 3D4/31 cells incubated at 37°C in the presence and absence of nocodazole (60ng/ml nocodazole (Sigma) for 16h), a microtubule inhibitor, or incubated at 10°C. In approximately 10% of cells expressing EGFP-PRRSV-N protein fluorescence was observed in the cytoplasm, but only if imaging was adjusted so that the fluorescent signal in the nucleus/nucleolus was above the linear range (for example Fig. 8C, lower panels) . abstract: Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. The dynamic trafficking of positive strand RNA virus nucleocapsid proteins and PRRSV N protein in particular between the cytoplasm and nucleolus is unknown. In this study live imaging of permissive and non-permissive cell lines, in conjunction with photo-bleaching (FRAP and FLIP), was used to investigate the trafficking of fluorescent labeled (EGFP) PRRSV-N protein. The data indicated that EGFP-PRRSV-N protein was not permanently sequestered to the nucleolus and had equivalent mobility to cellular nucleolar proteins. Further the nuclear import of N protein appeared to occur faster than nuclear export, which may account for the observed relative distribution of N protein between the cytoplasm and the nucleolus. url: https://www.ncbi.nlm.nih.gov/pubmed/18550142/ doi: 10.1016/j.virol.2008.04.037 id: cord-298242-iuskpoug author: Yu, Alvin title: A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion date: 2020-10-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Computer simulations of complete viral particles can provide theoretical insights into large-scale viral processes including assembly, budding, egress, entry, and fusion. Detailed atomistic simulations, however, are constrained to shorter timescales and require billion-atom simulations for these processes. Here, we report the current status and on-going development of a largely “bottom-up” coarse-grained (CG) model of the SARS-CoV-2 virion. Structural data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion model. We describe how CG molecular interactions can be derived from all-atom simulations, how viral behavior difficult to capture in atomistic simulations can be incorporated into the CG models, and how the CG models can be iteratively improved as new data becomes publicly available. Our initial CG model and the detailed methods presented are intended to serve as a resource for researchers working on COVID-19 who are interested in performing multiscale simulations of the SARS-CoV-2 virion. Significance Statement This study reports the construction of a molecular model for the SARS-CoV-2 virion and details our multiscale approach towards model refinement. The resulting model and methods can be applied to and enable the simulation of SARS-CoV-2 virions. url: https://www.ncbi.nlm.nih.gov/pubmed/33024966/ doi: 10.1101/2020.10.02.323915 id: cord-002739-7t1o19kn author: Yu, Xiaobo title: Multiplexed Nucleic Acid Programmable Protein Arrays date: 2017-09-20 words: 6451.0 sentences: 296.0 pages: flesch: 49.0 cache: ./cache/cord-002739-7t1o19kn.txt txt: ./txt/cord-002739-7t1o19kn.txt summary: Methods: In this work, we developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA), which significantly increases the number of displayed proteins by multiplexing as many as five different gene plasmids within a printed spot. Protein-protein interactions and serological antibody assays using human viral proteome microarrays demonstrated that comparable hits were detected by M-NAPPA and non-multiplexed NAPPA arrays. We developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA) method by combining as many as five different DNA plasmids within one spot, which increases the number of displayed proteins per microarray by five-fold. To decrease the cost of high throughput screening experiments, we hypothesized that the plasmid cDNA encoding for different proteins could be multiplexed (by combining M different plasmids) within each feature to create a high-density array, M-NAPPA ( Figure 1A) . Since the multiplex concept to increase feature density was successful in detecting protein-protein interactions and serological antibody responses on planar microarrays, we wanted to determine whether M-NAPPA could also be applied to a nano-well microarray platform. abstract: Rationale: Cell-free protein microarrays display naturally-folded proteins based on just-in-time in situ synthesis, and have made important contributions to basic and translational research. However, the risk of spot-to-spot cross-talk from protein diffusion during expression has limited the feature density of these arrays. Methods: In this work, we developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA), which significantly increases the number of displayed proteins by multiplexing as many as five different gene plasmids within a printed spot. Results: Even when proteins of different sizes were displayed within the same feature, they were readily detected using protein-specific antibodies. Protein-protein interactions and serological antibody assays using human viral proteome microarrays demonstrated that comparable hits were detected by M-NAPPA and non-multiplexed NAPPA arrays. An ultra-high density proteome microarray displaying > 16k proteins on a single microscope slide was produced by combining M-NAPPA with a photolithography-based silicon nano-well platform. Finally, four new tuberculosis-related antigens in guinea pigs vaccinated with Bacillus Calmette-Guerin (BCG) were identified with M-NAPPA and validated with ELISA. Conclusion: All data demonstrate that multiplexing features on a protein microarray offer a cost-effective fabrication approach and have the potential to facilitate high throughput translational research. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667425/ doi: 10.7150/thno.20151 id: cord-012682-7goljir4 author: Yuan, Meng title: N-myristoylation: from cell biology to translational medicine date: 2020-03-18 words: 7187.0 sentences: 347.0 pages: flesch: 38.0 cache: ./cache/cord-012682-7goljir4.txt txt: ./txt/cord-012682-7goljir4.txt summary: N-myristoylation refers to the attachment of 14-carbon fatty acid myristates to the N-terminal glycine of proteins by N-myristoyltransferases (NMT) and affects their physiology such as plasma targeting, subcellular tracking and localization, thereby influencing the function of proteins. For example, it was reported that both N-myristoylation and palmitoylation appear to have opposing roles and different membrane lipid microdomain preferences for the G protein-membrane interactions I (Gαi1) monomer, which are likely due to the conformational differences in the presence of different fatty acids [31] . Potential targets of cancer treatments Given that altered NMT expression is observed in many types of cancer tissues and because many N-myristoylated proteins are involved in signaling processes that regulate cell proliferation, growth and death, it has been proposed that N-myristoylation or NMTs can be considered as therapeutic targets for cancer. abstract: Various lipids and lipid metabolites are bound to and modify the proteins in eukaryotic cells, which are known as ‘protein lipidation’. There are four major types of the protein lipidation, i.e. myristoylation, palmitoylation, prenylation, and glycosylphosphatidylinositol anchor. N-myristoylation refers to the attachment of 14-carbon fatty acid myristates to the N-terminal glycine of proteins by N-myristoyltransferases (NMT) and affects their physiology such as plasma targeting, subcellular tracking and localization, thereby influencing the function of proteins. With more novel pathogenic N-myristoylated proteins are identified, the N-myristoylation will attract great attentions in various human diseases including infectious diseases, parasitic diseases, and cancers. In this review, we summarize the current understanding of N-myristoylation in physiological processes and discuss the hitherto implication of crosstalk between N-myristoylation and other protein modification. Furthermore, we mention several well-studied NMT inhibitors mainly in infectious diseases and cancers and generalize the relation of NMT and cancer progression by browsing the clinic database. This review also aims to highlight the further investigation into the dynamic crosstalk of N-myristoylation in physiological processes as well as the potential application of protein N-myristoylation in translational medicine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468318/ doi: 10.1038/s41401-020-0388-4 id: cord-297324-me5ff1pb author: Zeng, Rong title: Characterization of the 3a Protein of SARS-associated Coronavirus in Infected Vero E6 Cells and SARS Patients() date: 2004-07-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Proteomics was used to identify a protein encoded by ORF 3a in a SARS-associated coronavirus (SARS-CoV). Immuno-blotting revealed that interchain disulfide bonds might be formed between this protein and the spike protein. ELISA indicated that sera from SARS patients have significant positive reactions with synthesized peptides derived from the 3a protein. These results are concordant with that of a spike protein-derived peptide. A tendency exists for co-mutation between the 3a protein and the spike protein of SARS-CoV isolates, suggesting that the function of the 3a protein correlates with the spike protein. Taken together, the 3a protein might be tightly correlated to the spike protein in the SARS-CoV functions. The 3a protein may serve as a new clinical marker or drug target for SARS treatment. url: https://www.ncbi.nlm.nih.gov/pubmed/15312778/ doi: 10.1016/j.jmb.2004.06.016 id: cord-347661-q9lgliph author: Zevenhoven-Dobbe, Jessika C. title: Production of Monospecific Rabbit Antisera Recognizing Nidovirus Proteins date: 2007-11-28 words: 6866.0 sentences: 343.0 pages: flesch: 53.0 cache: ./cache/cord-347661-q9lgliph.txt txt: ./txt/cord-347661-q9lgliph.txt summary: The use as antigens of either synthetic peptides (coupled to a carrier protein) or proteins expressed in Escherichia coli is described, and detailed protocols for immunization and preparation of test bleeds are provided. Furthermore, in the context of specific research questions, polyclonal antisera may sometimes even be preferred over monoclonal antibodies since they contain a mixture of immunoglobulin molecules, derived from different B-cell lines in the immunized animal, often recognizing multiple epitopes of the target protein. The antiserum used here was raised against a domain in the C-terminal region of pp1a of the arterivirus EAV (8) and recognizes a large set of processing intermediates and end products, which are indicated by arrowheads: (A) Western blot analysis: EAV-and mock-infected cell lysates were prepared at 8 h postinfection, run on an SDS-polyacrylamide gel, blotted to PVDF membrane, and incubated with the postimmune serum at a 1:1000 dilution. abstract: The importance of monospecific antisera for the experimental analysis of viral proteins is undisputed. They make it possible to identify and analyze the target protein against a background of a large number of other proteins, either in whole fixed cells or in cell lysates. This chapter describes our experience with the production of such rabbit antisera directed against proteins of coronaviruses and other nidoviruses. The use as antigens of either synthetic peptides (coupled to a carrier protein) or proteins expressed in Escherichia coli is described, and detailed protocols for immunization and preparation of test bleeds are provided. For screening of the immune response following immunization, detailed protocols for three commonly used techniques are described, all of which are based on the use of infected cells or cells expressing the protein of interest, side by side with appropriate controls. The in situ immunodetection of the target in fixed cells by immunofluorescence microscopy is described, as are protocols for techniques that can be applied to cell lysates containing the target protein (Western blotting and immunoprecipitation). The latter techniques are performed in combination with polyacrylamide gel electrophoresis, thus allowing confirmation of the molecular weight of the target that is recognized by the antiserum. url: https://www.ncbi.nlm.nih.gov/pubmed/19057875/ doi: 10.1007/978-1-59745-181-9_16 id: cord-284990-klsl1nzn author: Zhang, Dapeng title: A novel immunity system for bacterial nucleic acid degrading toxins and its recruitment in various eukaryotic and DNA viral systems date: 2011-02-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The use of nucleases as toxins for defense, offense or addiction of selfish elements is widely encountered across all life forms. Using sensitive sequence profile analysis methods, we characterize a novel superfamily (the SUKH superfamily) that unites a diverse group of proteins including Smi1/Knr4, PGs2, FBXO3, SKIP16, Syd, herpesviral US22, IRS1 and TRS1, and their bacterial homologs. Using contextual analysis we present evidence that the bacterial members of this superfamily are potential immunity proteins for a variety of toxin systems that also include the recently characterized contact-dependent inhibition (CDI) systems of proteobacteria. By analyzing the toxin proteins encoded in the neighborhood of the SUKH superfamily we predict that they possess domains belonging to diverse nuclease and nucleic acid deaminase families. These include at least eight distinct types of DNases belonging to HNH/EndoVII- and restriction endonuclease-fold, and RNases of the EndoU-like and colicin E3-like cytotoxic RNases-folds. The N-terminal domains of these toxins indicate that they are extruded by several distinct secretory mechanisms such as the two-partner system (shared with the CDI systems) in proteobacteria, ESAT-6/WXG-like ATP-dependent secretory systems in Gram-positive bacteria and the conventional Sec-dependent system in several bacterial lineages. The hedgehog-intein domain might also release a subset of toxic nuclease domains through auto-proteolytic action. Unlike classical colicin-like nuclease toxins, the overwhelming majority of toxin systems with the SUKH superfamily is chromosomally encoded and appears to have diversified through a recombination process combining different C-terminal nuclease domains to N-terminal secretion-related domains. Across the bacterial superkingdom these systems might participate in discriminating `self’ or kin from `non-self’ or non-kin strains. Using structural analysis we demonstrate that the SUKH domain possesses a versatile scaffold that can be used to bind a wide range of protein partners. In eukaryotes it appears to have been recruited as an adaptor to regulate modification of proteins by ubiquitination or polyglutamylation. Similarly, another widespread immunity protein from these toxin systems, namely the suppressor of fused (SuFu) superfamily has been recruited for comparable roles in eukaryotes. In animal DNA viruses, such as herpesviruses, poxviruses, iridoviruses and adenoviruses, the ability of the SUKH domain to bind diverse targets has been deployed to counter diverse anti-viral responses by interacting with specific host proteins. url: https://doi.org/10.1093/nar/gkr036 doi: 10.1093/nar/gkr036 id: cord-103709-86hv27vh author: Zhang, Dong Yan title: Prefusion spike protein stabilization through computational mutagenesis date: 2020-06-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has emerged as a human pathogen, causing global pandemic and resulting in over 400,000 deaths worldwide. The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2). Due to the critical role in viral-host interaction and the exposure of spike protein, it has been a focus of most vaccines’ developments. However, the structural and biochemical studies of the spike protein are challenging because it is thermodynamically metastable1. Here, we develop a new pipeline that automatically identifies mutants that thermodynamically stabilize the spike protein. Our pipeline integrates bioinformatics analysis of conserved residues, motion dynamics from molecular dynamics simulations, and other structural analysis to identify residues that significantly contribute to the thermodynamic stability of the spike protein. We then utilize our previously developed protein design tool, Eris, to predict thermodynamically stabilizing mutations in proteins. We validate the ability of our pipeline to identify protein stabilization mutants through known prefusion spike protein mutants. We finally utilize the pipeline to identify new prefusion spike protein stabilization mutants. url: https://doi.org/10.1101/2020.06.17.157081 doi: 10.1101/2020.06.17.157081 id: cord-349774-898tmq14 author: Zhang, Haiyang title: Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein date: 2020-06-16 words: 3172.0 sentences: 188.0 pages: flesch: 52.0 cache: ./cache/cord-349774-898tmq14.txt txt: ./txt/cord-349774-898tmq14.txt summary: title: Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein Here, we report for the first time that the 11S proteasomal activator PA28γ regulates the intracellular abundance of the SARS-CoV-2 N protein (nCoV N). These results suggest that PA28γ binding is important in regulating 20S proteasome activity, which in turn regulates levels of the critical nCoV N nucleocapsid protein of SARS-CoV-2, furthering our understanding of the pathogenesis of COVID-19. The SARS-CoV-2 nucleocapsid protein (hereafter, referred to as nCoV N) accounts for the largest proportion of viral structure proteins and is the most abundant protein in virus-infected cells. PA28γ could be critical for degrading the SARS-CoV-19 nCoV N protein in the nucleus as part of the 20S proteasome, which acts to degrade proteins in a ubiquitin-independent manner, such as seen in the hepatitis C virus (HCV) core protein [11] . Interactions of SARS Coronavirus Nucleocapsid Protein with the host cell proteasome subunit p42 abstract: The nucleocapsid protein is significant in the formation of viral RNA of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accounting for the largest proportion of viral structural proteins. Here, we report for the first time that the 11S proteasomal activator PA28γ regulates the intracellular abundance of the SARS-CoV-2 N protein (nCoV N). Furthermore, we have identified proteasome activator PA28γ as a nCoV N binding protein by co-immunoprecipitation assay. As a result of their interaction, nCoV N could be degraded by PA28γ-20S in vitro degradation assay. This was also demonstrated by blocking de novo protein synthesis with cycloheximide. The stability of nCoV N in PA28γ-knockout cells was greater than in PA28γ-wildtype cells. Notably, immunofluorescence staining revealed that knockout of the PA28γ gene in cells led to the transport of nCoV N from the nucleus to the cytoplasm. Overexpression of PA28γ enhanced proteolysis of nCoV N compared to that in PA28γ-N151Y cells containing a dominant-negative PA28γ mutation, which reduced this process. These results suggest that PA28γ binding is important in regulating 20S proteasome activity, which in turn regulates levels of the critical nCoV N nucleocapsid protein of SARS-CoV-2, furthering our understanding of the pathogenesis of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32703419/ doi: 10.1016/j.bbrc.2020.06.058 id: cord-024193-khdvj6t5 author: Zhang, Hong title: Peptide Arrays date: 2012-01-17 words: 11358.0 sentences: 486.0 pages: flesch: 41.0 cache: ./cache/cord-024193-khdvj6t5.txt txt: ./txt/cord-024193-khdvj6t5.txt summary: Despite the concern over the potential loss of structural information as a result of the use of peptides as opposed to proteins as molecular probes, peptide arrays have been implemented in a broad range of applications including antibody screening and epitope mapping, characterization of molecular interactions, and enzymatic activity profiling, and they have become a valuable tool for proteomics research. Similarly to DNA/oligonucleotide microarrays, arrays for proteomics studies feature a wide range of molecules including recombinant proteins, complex protein samples, antibodies, peptides, or small molecules that are assembled in an addressable fashion on planar surfaces to allow parallel interrogations for activity and interactions associated with biomolecules at the protein level. abstract: Despite the concern over the potential loss of structural information as a result of the use of peptides as opposed to proteins as molecular probes, peptide arrays have been implemented in a broad range of applications including antibody screening and epitope mapping, characterization of molecular interactions, and enzymatic activity profiling, and they have become a valuable tool for proteomics research. In this chapter, we first (Sect. 7.1) recapitulate the development of these arrays and highlight a couple of key improvements in the array production and the application in proteomics research. For clinical and biomarker development applications, it is important to measure entities that are directly related to physiological function (and dysfunction). In this respect, the assessment of enzymatic activities is obviously preferable to genotyping, expression profiling, or even measurement of protein amounts. In Sect. 7.2, an original technology based on peptides arrayed onto a porous support allows detailed profiling of kinase activities in a biological sample. The applications described range from kinase characterization to inhibition profiles, detection of off-target effects, and drug response prediction in a clinical setting, allowing rational choice of the drug to be used. Such directly functional approaches will have an important role in the transition to more personalized medicine. Finally, in Sect. 7.3, a recently developed method for “laser printing” of peptide arrays that will make these approaches much more practical is presented. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193736/ doi: 10.1007/978-3-642-28203-4_7 id: cord-300884-rqfxe0x1 author: Zhang, Jianqiang title: Genomic characterization of equine coronavirus date: 2007-12-05 words: 6804.0 sentences: 378.0 pages: flesch: 56.0 cache: ./cache/cord-300884-rqfxe0x1.txt txt: ./txt/cord-300884-rqfxe0x1.txt summary: Analysis of the sequence identified 11 open reading frames which encode two replicase polyproteins, five structural proteins (hemagglutinin esterase, spike, envelope, membrane, and nucleocapsid) and four accessory proteins (NS2, p4.7, p12.7, and I). In contrast to the replicase proteins which are directly translated from the genomic RNA, coronavirus structural and accessory proteins are expressed from a nested set of 3′ coterminal subgenomic (sg) mRNAs that also possess a common 5′ leader sequence derived from the 5′ end of the genome (Pasternak et al., 2006; Sawicki et al., 2007) . Following multiple alignments with the S proteins of other group 2a coronaviruses, a potential cleavage recognition sequence (RRQRR) was identified at residues 764-768 which would predict a cleavage between amino acids 768 and 769, separating the ECoV S protein into S1 and S2 subunits (Fig. 1) . abstract: The complete genome sequence of the first equine coronavirus (ECoV) isolate, NC99 strain was accomplished by directly sequencing 11 overlapping fragments which were RT–PCR amplified from viral RNA. The ECoV genome is 30,992 nucleotides in length, excluding the polyA tail. Analysis of the sequence identified 11 open reading frames which encode two replicase polyproteins, five structural proteins (hemagglutinin esterase, spike, envelope, membrane, and nucleocapsid) and four accessory proteins (NS2, p4.7, p12.7, and I). The two replicase polyproteins are predicted to be proteolytically processed by three virus-encoded proteases into 16 non-structural proteins (nsp1–16). The ECoV nsp3 protein had considerable amino acid deletions and insertions compared to the nsp3 proteins of bovine coronavirus, human coronavirus OC43, and porcine hemagglutinating encephalomyelitis virus, three group 2 coronaviruses phylogenetically most closely related to ECoV. The structure of subgenomic mRNAs was analyzed by Northern blot analysis and sequencing of the leader–body junction in each sg mRNA. url: https://www.sciencedirect.com/science/article/pii/S0042682207004655 doi: 10.1016/j.virol.2007.06.035 id: cord-332317-wrztpeb8 author: Zhang, Xin title: Identification of the interaction between vimentin and nucleocapsid protein of transmissible gastroenteritis virus date: 2015-03-16 words: 3977.0 sentences: 241.0 pages: flesch: 49.0 cache: ./cache/cord-332317-wrztpeb8.txt txt: ./txt/cord-332317-wrztpeb8.txt summary: Nucleocapsid (N) protein of transmissible gastroenteritis virus (TGEV) packages viral RNA genome to form a ribonucleoprotein complex. The present study thus provides protein-related information about interaction of TGEV N protein with host cell that should be useful for understanding host cell response to coronavirus pathogenesis infection and the underlying mechanism of coronavirus replication. Recently, some reports showed that N protein of TGEV play an important role in host cell for virus replication. Three cellular proteins, hnRNP U, ACTN4, and vimentin, were identified both by GST-N pull down and Co-IP in TGEV-infected cells, which should have more biological importance in the context of infection. The interaction between the cellular vimentin and N protein of TGEV was confirmed in TGEV-infected ST cells. Host cell proteins interacting with the 3 end of TGEV coronavirus genome influence virus replication EF1A interacting with nucleocapsid protein of transmissible gastroenteritis coronavirus and plays a role in virus replication abstract: Nucleocapsid (N) protein of transmissible gastroenteritis virus (TGEV) packages viral RNA genome to form a ribonucleoprotein complex. In addition to its function as a structural protein, N protein is involved in cell apoptosis or cell-cycle regulation. N protein possibly interacts with host factors to modulate cellular functions. To identify cellular proteins that interacted with N protein of TGEV, methods of GST pull-down and Co-IP were utilized to precipitate cellular proteins of swine testicular (ST). Bound cellular proteins were resolved by SDS-PAGE. Analysis of interacting proteins by mass spectrometry allowed identification of 15 cellular protein bands representative of 12 cellular proteins including vimentin that bound to N protein. Furthermore, the function of vimentin cytoskeleton in ST cells during TGEV infection was examined. Vimentin cytoskeleton was required for virus replication. The present study thus provides protein-related information about interaction of TGEV N protein with host cell that should be useful for understanding host cell response to coronavirus pathogenesis infection and the underlying mechanism of coronavirus replication. url: https://www.ncbi.nlm.nih.gov/pubmed/25533531/ doi: 10.1016/j.virusres.2014.12.013 id: cord-257392-u6jy6w1m author: Zhao, Yanfeng title: Proteomic analysis of primary duck hepatocytes infected with duck hepatitis B virus date: 2010-06-07 words: 6033.0 sentences: 294.0 pages: flesch: 41.0 cache: ./cache/cord-257392-u6jy6w1m.txt txt: ./txt/cord-257392-u6jy6w1m.txt summary: In this report, we explored global changes in cellular protein expression in DHBV infected PDHs by two-dimension gel electrophoresis (2-DE) combined with MALDI-TOF/TOF tandem mass spectrometry (MS/MS). The down-regulated expression of beta-actin and annexin A2 was confirmed by Western blot analysis, and potential roles of some differentially expressed proteins in the virus-infected cells have been discussed. CONCLUSIONS: Differentially expressed proteins of DHBV infected PDHs revealed by 2-DE, are involved in carbohydrate metabolism, amino acid metabolism, stress responses and cytoskeleton processes etc, providing the insight to understanding of interactions between hepadnavirus and hepatocytes and molecular mechanisms of hepadnavirus pathogenesis. Expression levels of annexin A2, beta-actin, Hsp70, destrin, and lamin A were validated by Western blot analysis to confirm the dynamic alterations of protein expression during DHBV infection. In summary, the present study explored global changes in cellular protein expression of hepadnavirus infection by 2-DE analysis, using a natural DHBV-PDHs infection system. abstract: BACKGROUND: Hepatitis B virus (HBV) is a major cause of liver infection in human. Because of the lack of an appropriate cell culture system for supporting HBV infection efficiently, the cellular and molecular mechanisms of hepadnavirus infection remain incompletely understood. Duck heptatitis B virus (DHBV) can naturally infect primary duck hepatocytes (PDHs) that provide valuable model systems for studying hepadnavirus infection in vitro. In this report, we explored global changes in cellular protein expression in DHBV infected PDHs by two-dimension gel electrophoresis (2-DE) combined with MALDI-TOF/TOF tandem mass spectrometry (MS/MS). RESULTS: The effects of hepadnavirus infection on hepatocytes were investigated in DHBV infected PDHs by the 2-DE analysis. Proteomic profile of PDHs infected with DHBV were analyzed at 24, 72 and 120 h post-infection by comparing with uninfected PDHs, and 75 differentially expressed protein spots were revealed by 2-DE analysis. Among the selected protein spots, 51 spots were identified corresponding to 42 proteins by MS/MS analysis; most of them were matched to orthologous proteins of Gallus gallus, Anas platyrhynchos or other avian species, including alpha-enolase, lamin A, aconitase 2, cofilin-2 and annexin A2, etc. The down-regulated expression of beta-actin and annexin A2 was confirmed by Western blot analysis, and potential roles of some differentially expressed proteins in the virus-infected cells have been discussed. CONCLUSIONS: Differentially expressed proteins of DHBV infected PDHs revealed by 2-DE, are involved in carbohydrate metabolism, amino acid metabolism, stress responses and cytoskeleton processes etc, providing the insight to understanding of interactions between hepadnavirus and hepatocytes and molecular mechanisms of hepadnavirus pathogenesis. url: https://doi.org/10.1186/1477-5956-8-28 doi: 10.1186/1477-5956-8-28 id: cord-271693-7tg21up3 author: Zheng, Fan title: Identifying persistent structures in multiscale ‘omics data date: 2020-10-03 words: 4889.0 sentences: 291.0 pages: flesch: 48.0 cache: ./cache/cord-271693-7tg21up3.txt txt: ./txt/cord-271693-7tg21up3.txt summary: Many different approaches have been devised or applied to detect structures in biological data, including standard clustering, network community detection, and low-dimensional data projection [5] [6] [7] , some of which can be tuned for sensitivity to objects of a certain size or scale (so-called ''resolution parameters'') [8, 9] . We first explored the idea of measuring community persistence via analysis of synthetic datasets [15] in which communities were simulated and embedded in the similarity network at two different scales (Supplementary Fig. 1a; Methods) . Application to protein-protein interaction networks from budding yeast and human found that HiDeF captured knowledge in GO more significantly than previous pipelines proposed for this task, including the NeXO approach to hierarchical community detection [23] and standard hierarchical clustering of pairwise protein distances calculated by three recent network embedding approaches [24] [25] [26] (Fig. 3a, Fig. 7) . abstract: In any ‘omics study, the scale of analysis can dramatically affect the outcome. For instance, when clustering single-cell transcriptomes, is the analysis tuned to discover broad or specific cell types? Likewise, protein communities revealed from protein networks can vary widely in sizes depending on the method. Here we use the concept of “persistent homology”, drawn from mathematical topology, to identify robust structures in data at all scales simultaneously. Application to mouse single-cell transcriptomes significantly expands the catalog of identified cell types, while analysis of SARS-COV-2 protein interactions suggests hijacking of WNT. The method, HiDeF, is available via Python and Cytoscape. url: https://www.ncbi.nlm.nih.gov/pubmed/32587977/ doi: 10.1101/2020.06.16.151555 id: cord-290904-ngvhk0qy author: Zheng, Zhiqiang title: Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2 date: 2020-07-16 words: 4471.0 sentences: 246.0 pages: flesch: 57.0 cache: ./cache/cord-290904-ngvhk0qy.txt txt: ./txt/cord-290904-ngvhk0qy.txt summary: In this study, we aim to verify if the sequence of the immunogen used to generate mAb 1A9, as well as three other mAbs, is conserved in different coronaviruses and if these mAbs bind to the S protein of SARS-CoV-2 expressed in mammalian cell lines. IF analysis performed on transiently transfected COS-7 cells showed binding of the four mAbs to this S protein fragment of SARS-CoV-2 ( Figure 2B ). Utility of monoclonal antibody 1A9 for detection of S protein in a sandwich ELISA format and in SARS-CoV-2 infected cells Based on indirect ELISA data, mAb 1A9 has the strongest binding to S protein when compared with the other three mAbs. Hence, a sandwich ELISA was performed to determine if it can be paired with the human mAb CR3022 which is known to bind to the S1 subunit of SARS-CoV-2. abstract: BACKGROUND: A novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002–2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2. AIM: The cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed. METHODS: The SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein. RESULTS: An immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format. CONCLUSION: The cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32700671/ doi: 10.2807/1560-7917.es.2020.25.28.2000291 id: cord-271470-j58mr9xk author: Zhu, Feifei title: Glycoproteome in silkworm Bombyx mori and alteration by BmCPV infection date: 2020-04-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The biological functions of protein glycosylation have been increasingly recognized but not yet been very well understood, especially in lower organisms. Silkworm as a model lepidopteran insect and important economic insect, has been widely studied in life science, however, the current knowledge on the glycosylation status of its proteome is not satisfactory, and little is known about how pathogenic infections could affect the glycosylation status. This study performed large scale glycosite mapping for the silkworm Bombyx mori P50 strain, and quantitatively compared with that infected with the Bombyx mori cytoplasmic polyhedrosis virus (BmCPV). Some 400 glycoproteins were mapped in the silkworm, including N- and O-glycoproteins. Upon virus infection, the glycosylation levels of 41 N-glycopeptides were significantly changed, some of them belonging to transmembrane glycoproteins. The O-glycosylation profiles were also affected. In addition, 4 BmCPV-encoded viral proteins were found to be glycosylated for the first time, including polyhedrin, P101, VP3, and the NS protein. This study drafted a silkworm protein glycosylation map and underlined the potential impact of virus infection on glycosylation. Significance This study reveals the characteristics of the glycoproteome in the silkworm strain P50, and quantitatively compared to that infected by the virus BmCPV, which underlines the impact of virus infection on the alteration of protein glycosylation in invertebrate species. Our findings add to the knowledge of the post translational modifications of this model organism, and also uncovered for the first time the glycosylation status of the viral proteins expressed by BmCPV. url: https://api.elsevier.com/content/article/pii/S1874391920301706 doi: 10.1016/j.jprot.2020.103802 id: cord-048344-ps3mnpzq author: Zhu, Xiaowei title: ProCAT: a data analysis approach for protein microarrays date: 2006-11-16 words: 5728.0 sentences: 300.0 pages: flesch: 48.0 cache: ./cache/cord-048344-ps3mnpzq.txt txt: ./txt/cord-048344-ps3mnpzq.txt summary: Here we report a new approach, ProCAT, which corrects for background bias and spatial artifacts, identifies significant signals, filters nonspecific spots, and normalizes the resulting signal to protein abundance. In addition, spatial variations can be reduced efficiently through a novel two-parameter signal normalization approach and calling positive spots locally. A scaling method that reduces signal variations among spots of the same proteins at different array locations decreases spatial artifacts. The average values are then used to correct the signal of the central spot to To test the performance of this two-parameter scaling approach for signal normalization within one slide, we designed a test microarray containing multiple positive controls printed at different positions on the slide. Processed data including analysis parameters, a list of positive spots with protein annotations, and normalized signal intensities will be available for the users to download from the server. abstract: Protein microarrays provide a versatile method for the analysis of many protein biochemical activities. Existing DNA microarray analytical methods do not translate to protein microarrays due to differences between the technologies. Here we report a new approach, ProCAT, which corrects for background bias and spatial artifacts, identifies significant signals, filters nonspecific spots, and normalizes the resulting signal to protein abundance. ProCAT provides a powerful and flexible new approach for analyzing many types of protein microarrays. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794587/ doi: 10.1186/gb-2006-7-11-r110 id: cord-305143-mqd4ioj4 author: Zmasek, Christian M. title: Classification of human Herpesviridae proteins using Domain-architecture Aware Inference of Orthologs (DAIO) date: 2019-01-06 words: 7266.0 sentences: 367.0 pages: flesch: 44.0 cache: ./cache/cord-305143-mqd4ioj4.txt txt: ./txt/cord-305143-mqd4ioj4.txt summary: Coupled with their genome complexity and the availability of numerous complete genome sequences, this deep evolutionary history makes herpesviruses a tractable and informative model to study virus genome evolution at the levels of gene duplication and protein domain rearrangement. In addition, the gene tree for human herpesvirus uracil DNA glycosylases ( Fig. 1B ) precisely recapitulates the herpesvirus species tree (Fig. 1A) ; therefore, this protein family can be inferred to have evolved from a single common ancestor and without any gene duplications or domain rearrangements (see Table 2 for virus-specific gene names). Phylogenetic analysis of human herpesvirus DNA polymerase proteins, plus related proteins from selected mammalian herpesviruses, shows that, similar to the glycoprotein B family, DNA polymerases of the Herpesviride evolved without gene duplication. abstract: We developed a computational approach called Domain-architecture Aware Inference of Orthologs (DAIO) for the analysis of protein orthology by combining phylogenetic and protein domain-architecture information. Using DAIO, we performed a systematic study of the proteomes of all human Herpesviridae species to define Strict Ortholog Groups (SOGs). In addition to assessing the taxonomic distribution for each protein based on sequence similarity, we performed a protein domain-architecture analysis for every protein family and computationally inferred gene duplication events. While many herpesvirus proteins have evolved without any detectable gene duplications or domain rearrangements, numerous herpesvirus protein families do exhibit complex evolutionary histories. Some proteins acquired additional domains (e.g., DNA polymerase), whereas others show a combination of domain acquisition and gene duplication (e.g., betaherpesvirus US22 family), with possible functional implications. This novel classification system of SOGs for human Herpesviridae proteins is available through the Virus Pathogen Resource (ViPR, www.viprbrc.org). url: https://www.sciencedirect.com/science/article/pii/S0042682219300054 doi: 10.1016/j.virol.2019.01.005 id: cord-284208-8fsqgkw5 author: Zolla, Lello title: Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins date: 2008-11-07 words: 6987.0 sentences: 306.0 pages: flesch: 35.0 cache: ./cache/cord-284208-8fsqgkw5.txt txt: ./txt/cord-284208-8fsqgkw5.txt summary: In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. abstract: The most abundant proteins in serum, such as albumin and IgG, act as molecular sponges that bind and transport low molecular weight proteins/peptides and drugs. In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. Advances in these fields will open new avenues of tailor-made molecular therapy, reducing present limitations on treatment arising from toxicity and inefficiency. In this short review we report and discuss the most recent developments arising from the use of proteomic tools in blood plasma protein research, looking at the identification of proteins found in plasma as well as their interactions with small molecules such as drugs, peptides, organic chemicals and metals. We believe this research demonstrates that proteomic technologies, and in particular pharmacoproteomics, interactomics and post-translational modification analysis, could be instrumental in the design of new tailor-made drugs leading to substantial improvements in molecular therapy. url: https://doi.org/10.1016/j.drudis.2008.09.013 doi: 10.1016/j.drudis.2008.09.013 id: cord-269011-230p8rsf author: de Haan, Cornelis A.M. title: Molecular Interactions in the Assembly of Coronaviruses date: 2005-08-31 words: 22956.0 sentences: 1052.0 pages: flesch: 46.0 cache: ./cache/cord-269011-230p8rsf.txt txt: ./txt/cord-269011-230p8rsf.txt summary: Biochemical and theoretical studies led to a topological model for the MHV M protein Rottier et al., 1984 Rottier et al., , 1986 , in which the polypeptide spans the lipid bilayer three times, leaving a small amino-terminal domain (15-35 residues) in the lumen of intracellular organelles (or outside the virus), whereas the carboxyterminal half of the protein is located on the cytoplasmic side of the membrane (or inside the virion). Using a mutational approach including deletions, insertions, and substitutions, both the transmembrane domain and the cysteine-rich region immediately downstream thereof, but not the carboxy-terminal part of the cytoplasmic tail, were shown to be important for MHV S protein-induced cell-cell fusion (Bos et al., 1995; Chang and Gombold, 2001; Chang et al., 2000) The cleavage requirements of the S proteins for the biological activities of the coronavirus spike remain enigmatic. abstract: This chapter describes the interactions between the different structural components of the viruses and discusses their relevance for the process of virion formation. Two key factors determine the efficiency of the assembly process: intracellular transport and molecular interactions. Many viruses have evolved elaborate strategies to ensure the swift and accurate delivery of the virion components to the cellular compartment(s) where they must meet and form (sub) structures. Assembly of viruses starts in the nucleus by the encapsidation of viral DNA, using cytoplasmically synthesized capsid proteins; nucleocapsids then migrate to the cytosol, by budding at the inner nuclear membrane followed by deenvelopment, to pick up the tegument proteins. url: https://www.sciencedirect.com/science/article/pii/S0065352705640067 doi: 10.1016/s0065-3527(05)64006-7 id: cord-317675-s1ac5vcx author: de Marco, Ario title: Strategies for successful recombinant expression of disulfide bond-dependent proteins in Escherichia coli date: 2009-05-14 words: 11534.0 sentences: 524.0 pages: flesch: 31.0 cache: ./cache/cord-317675-s1ac5vcx.txt txt: ./txt/cord-317675-s1ac5vcx.txt summary: The cytoplasmic accumulation of thioredoxin as a consequence of its recombinant overexpression in wild type bacteria was proposed for increasing the yields of coexpressed eukaryotic proteins without disulfide bonds in their native structure [191] . Fusions between recombinant scFvs and thioredoxin 1 expressed in trxB -, gorbacteria resulted in increased cytoplasmic yields [196] , correct folding of a scFv against the c-Met receptor [188] , and of the first domain of the multiple Kazal-type inhibitor LEKTI, a polypeptide that contains two disulfide bridges in its native structure [197] . In the case of a serpin domain, AD494 cells did not improve the total amount of soluble recombinant protein accumulated in the cytoplasm with respect to wild type bacteria, but it was correctly folded and active, whilst the protein expressed in the control cells did not form the essential disulfide bonds [210] . abstract: Bacteria are simple and cost effective hosts for producing recombinant proteins. However, their physiological features may limit their use for obtaining in native form proteins of some specific structural classes, such as for instance polypeptides that undergo extensive post-translational modifications. To some extent, also the production of proteins that depending on disulfide bridges for their stability has been considered difficult in E. coli. Both eukaryotic and prokaryotic organisms keep their cytoplasm reduced and, consequently, disulfide bond formation is impaired in this subcellular compartment. Disulfide bridges can stabilize protein structure and are often present in high abundance in secreted proteins. In eukaryotic cells such bonds are formed in the oxidizing environment of endoplasmic reticulum during the export process. Bacteria do not possess a similar specialized subcellular compartment, but they have both export systems and enzymatic activities aimed at the formation and at the quality control of disulfide bonds in the oxidizing periplasm. This article reviews the available strategies for exploiting the physiological mechanisms of bactera to produce properly folded disulfide-bonded proteins. url: https://doi.org/10.1186/1475-2859-8-26 doi: 10.1186/1475-2859-8-26 id: cord-031957-df4luh5v author: dos Santos-Silva, Carlos André title: Plant Antimicrobial Peptides: State of the Art, In Silico Prediction and Perspectives in the Omics Era date: 2020-09-02 words: 16609.0 sentences: 954.0 pages: flesch: 43.0 cache: ./cache/cord-031957-df4luh5v.txt txt: ./txt/cord-031957-df4luh5v.txt summary: 19 Plant AMPs are the central focus of the present review, comprising information on their structural features (at genomic, gene, and protein levels), resources, and bioinformatic tools available, besides the proposition of an annotation routine. 26 Plant AMPs are also classified into families considering protein sequence similarity, cysteine motifs, and distinctive patterns of disulfide bonds, which determine the folding of the tertiary structure. 27, 31 These AMP categories will be detailed in the next sections, together with other groups here considered (Impatienlike, Macadamia [β-barrelins], Puroindoline (PIN), and Thaumatin-like protein [TLP]) and the recently described αhairpinin AMPs. The description includes comments on their structure, pattern for regular expression (REGEX) analysis (when available), functions, tissue-specificity, and scientific data availability. 179 As to the TLP structure, this protein presents characteristic thaumatin signature (PS00316): 180, 181 Most of the TLPs have molecular mass ranging from 21 to 26 kDa, 163 possessing 16 conserved cysteine residues (Supplementary Figure S8) involved in the formation of 8 disulfide bonds, 182 which help in the stability of the molecule, allowing a correct folding even under extreme conditions of temperature and pH. abstract: Even before the perception or interaction with pathogens, plants rely on constitutively guardian molecules, often specific to tissue or stage, with further expression after contact with the pathogen. These guardians include small molecules as antimicrobial peptides (AMPs), generally cysteine-rich, functioning to prevent pathogen establishment. Some of these AMPs are shared among eukaryotes (eg, defensins and cyclotides), others are plant specific (eg, snakins), while some are specific to certain plant families (such as heveins). When compared with other organisms, plants tend to present a higher amount of AMP isoforms due to gene duplications or polyploidy, an occurrence possibly also associated with the sessile habit of plants, which prevents them from evading biotic and environmental stresses. Therefore, plants arise as a rich resource for new AMPs. As these molecules are difficult to retrieve from databases using simple sequence alignments, a description of their characteristics and in silico (bioinformatics) approaches used to retrieve them is provided, considering resources and databases available. The possibilities and applications based on tools versus database approaches are considerable and have been so far underestimated. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476358/ doi: 10.1177/1177932220952739 id: cord-001835-0s7ok4uw author: nan title: Abstracts of the 29th Annual Symposium of The Protein Society date: 2015-10-01 words: 138514.0 sentences: 6150.0 pages: flesch: 40.0 cache: ./cache/cord-001835-0s7ok4uw.txt txt: ./txt/cord-001835-0s7ok4uw.txt summary: Altogether, these results indicate that, although PHDs might be more selective for HIF as a substrate as it was initially thought, the enzymatic activity of the prolyl hydroxylases is possibly influenced by a number of other proteins that can directly bind to PHDs. Non-natural aminoacids via the MIO-enzyme toolkit Alina Filip 1 , Judith H Bartha-V ari 1 , Gergely B an oczy 2 , L aszl o Poppe 2 , Csaba Paizs 1 , Florin-Dan Irimie 1 1 Biocatalysis and Biotransformation Research Group, Department of Chemistry, UBB, 2 Department of Organic Chemistry and Technology An attractive enzymatic route to enantiomerically pure to the highly valuable a-or b-aromatic amino acids involves the use of aromatic ammonia lyases (ALs) and aminomutases (AMs). Continuing our studies of the effect of like-charged residues on protein-folding mechanisms, in this work, we investigated, by means of NMR spectroscopy and molecular-dynamics simulations, two short fragments of the human Pin1 WW domain [hPin1(14-24); hPin1(15-23)] and one single point mutation system derived from hPin1(14-24) in which the original charged residues were replaced with non-polar alanine residues. abstract: nan url: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pro.2823 doi: 10.1002/pro.2823 id: cord-004534-jqm1hxps author: nan title: Abstract date: 2009-06-09 words: 139023.0 sentences: 6450.0 pages: flesch: 42.0 cache: ./cache/cord-004534-jqm1hxps.txt txt: ./txt/cord-004534-jqm1hxps.txt summary: HIV-1 to efficiently complete a replication cycle has to integrate its genome into the host cellular DNA.After HIV-1 enters target cells,neosynthesized viral DNA forms along with other proteins the pre-integration complex (PIC).PICs are then transported into the nucleus where integration,catalyzed by the viral integrase,takes place.HIV-1 viral particles engineered to incorporate integrase fused to EGFP have proven effective to study PICs within nuclei of infected cells.In this study we report the live imaging analysis of nuclear PIC dynamics obtained by time-lapse microscopy.Intranuclear trajectories of IN-EGFP-labeled PIC were collected in three dimensions and examined by both mean squared displacement (MSD) and cage diameter (CD) analysis.In CD the maximum distances measured between two positions occupied by a PIC in a time window of 2 minutes were calculated while in our MSD analysis 5-minute long trajectory segments were considered.Remarkably,MSD revealed the presence of an underlying active transport mechanism.To test the possible role of actin filaments,PIC nuclear trafficking was analyzed in cells treated with latrunculin B (actin polymerization inhibitor).Preliminary results suggest that the disruption of actin function impairs the active nuclear movement of PICs. Second harmonic generation microscopy reveals sarcomere contractile dynamics of cardiomyocytes N. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079852/ doi: 10.1007/s00249-009-0478-1 id: cord-004584-bcw90f5b author: nan title: Abstracts: 8th EBSA European Biophysics Congress, August 23rd–27th 2011, Budapest, Hungary date: 2011-08-06 words: 106850.0 sentences: 5038.0 pages: flesch: 41.0 cache: ./cache/cord-004584-bcw90f5b.txt txt: ./txt/cord-004584-bcw90f5b.txt summary: Our goals are two-fold: (1) to monitor conformational changes in each domain upon its binding to specific ligands and then to correlate the observed changes with structural differences between the CRDs and (2) to investigate the interaction between the CRDs and lipid model membranes. Cholesterol-assisted lipid and protein interactions such as the integration into lipid nanodomains are considered to play a functional part in a whole range of membrane-associated processes, but their direct and non-invasive observation in living cells is impeded by the resolution limit of [200nm of a conventional far-field optical microscope. Therefore, to investigate the dynamic and complex membrane lateral organization in living cells, we have developed an original approach based on molecule diffusion measurements performed by fluorescence correlation spectroscopy at different spatial scales (spot variable FCS, svFCS) (1). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080017/ doi: 10.1007/s00249-011-0734-z id: cord-004879-pgyzluwp author: nan title: Programmed cell death date: 1994 words: 81677.0 sentences: 4465.0 pages: flesch: 51.0 cache: ./cache/cord-004879-pgyzluwp.txt txt: ./txt/cord-004879-pgyzluwp.txt summary: Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3'' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087532/ doi: 10.1007/bf02033112 id: cord-004948-ad3i9wgj author: nan title: 7th International Congress on Amino Acids and Proteins : Vienna, Austria, August 6–10, 2001 date: 2001 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087755/ doi: 10.1007/s007260170030 id: cord-006229-7yoilsho author: nan title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date: 2016-02-06 words: 133493.0 sentences: 6804.0 pages: flesch: 42.0 cache: ./cache/cord-006229-7yoilsho.txt txt: ./txt/cord-006229-7yoilsho.txt summary: It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100641/ doi: 10.1007/s00210-016-1213-y id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 words: 135419.0 sentences: 7042.0 pages: flesch: 43.0 cache: ./cache/cord-006230-xta38e7j.txt txt: ./txt/cord-006230-xta38e7j.txt summary: Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100643/ doi: 10.1007/s00210-012-0736-0 id: cord-006860-a3b8hyyr author: nan title: 40th Annual Meeting of the GTH (Gesellschaft für Thrombose- und Hämostaseforschung) date: 1996 words: 90660.0 sentences: 5152.0 pages: flesch: 50.0 cache: ./cache/cord-006860-a3b8hyyr.txt txt: ./txt/cord-006860-a3b8hyyr.txt summary: Dept of Pediatrics, University Hospitals Kiel and Mtinster, Germany Resistance to activated protein C (APCR), in the majority of cases associated with the Arg 506 Gin point mutation in the factor V gene is present in more than 50 % of patients < 60 years of age with unexplained thrombophilia. The regular APC resistance test is not applicable to plasma from Orally anticoagulated (OAC) or heparinized patients due to decreased levels of vitamin K-dependent clotting factors and to thrombin inhibition by antithrombin, respectively. On admission an extensive coagulation screen yielded the following results (n/normal, t/elevated, I/reduced, +/positive, -/negative): PT t, aPTT t, Tr n, factor II, V, VIII n, factor VII, IX, XI, XII /,, fibrinogan t, ATIII n, protein C, S *, activated protein C sensitivity ratio 1.92 ($), FV-Leidenmutation PCR -, fibrinolytic system n, TAT t, Ft÷2 t, lupus anticoagulant +, heparin induced platelet antibodies +; no diagnosis of a specific autoimmuna disorder could be made. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103196/ doi: 10.1007/bf00641048 id: cord-008777-i2reanan author: nan title: ECB12: 12th European Congess on Biotechnology date: 2005-07-19 words: 151383.0 sentences: 7577.0 pages: flesch: 43.0 cache: ./cache/cord-008777-i2reanan.txt txt: ./txt/cord-008777-i2reanan.txt summary: Mollerup Department of Chemical Engineering, Building 229, DTU, 2800 Lyngby, Denmark A variety of factors that govern the properties of proteins are utilized in the development of chromatographic processes for the recovery of biological products including the binding and release of protons, the non-covalent association with non-polar groups (often hydrophobic interactions), the association of small ions (ion exchange) and the highly specific antigen-antibody interaction (affinity interactions). Such fermenters will be needed in order to meet the increasing pressure on costs for low price commodity type products such as single cell protein or food and technical grade enzymes, and to meet the demands of the new wave of white biotech, in which bio-produced chemicals must be made at prices competitive with those of the traditional chemical industry. The presentation will focus on use of the sensitive sandwich hybridization technology for the quantitative analysis of process relevant marker genes in different kind of microbial cell cultures with a focus on the production of recombinant proteins. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134330/ doi: 10.1016/j.jbiotec.2005.06.005 id: cord-014368-4nasrbs6 author: nan title: Gene Chip for Viral Discovery date: 2003-11-17 words: 10009.0 sentences: 438.0 pages: flesch: 49.0 cache: ./cache/cord-014368-4nasrbs6.txt txt: ./txt/cord-014368-4nasrbs6.txt summary: As they report in this paper, Miguel Nicolelis and colleagues have helped clarify some of the fundamental issues surrounding the programming and use of BMIs. Presenting results from a series of long-term studies in monkeys, they demonstrate that the same set of brain cells can control two distinct movements, the reaching and grasping of a robotic arm. RAG genes regulate the genetic recombination and ultimate cell surface expression of TCRs. Using chemical inhibitors and mutant human T cell lines deficient in critical signaling components involved in antigen receptor-dependent pathways, the researchers found that the loss of specific functions or specific proteins affected an unexpected set of target genes. But these studies also establish a model for investigating other signaling systems, to determine whether biologically functional basal signaling is a rare phenomenon or whether it is a fundamental cell process needed to control the profile of gene expression in the quiescent state. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC261871/ doi: 10.1371/journal.pbio.0000003 id: cord-014462-11ggaqf1 author: nan title: Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh date: 2011-04-21 words: 35453.0 sentences: 1711.0 pages: flesch: 49.0 cache: ./cache/cord-014462-11ggaqf1.txt txt: ./txt/cord-014462-11ggaqf1.txt summary: Molecular diagnosis based on reverse transcription (RT)-PCR s.a. one step or nested PCR, nucleic acid sequence based amplification (NASBA), or real time RT-PCR, has gradually replaced the virus isolation method as the new standard for the detection of dengue virus in acute phase serum samples. Non-genetic methods of management of these diseases include quarantine measures, eradication of infected plants and weed hosts, crop rotation, use of certified virus-free seed or planting stock and use of pesticides to control insect vector populations implicated in transmission of viruses. The results of this study indicate that NS1 antigen based ELISA test can be an useful tool to detect the dengue virus infection in patients during the early acute phase of disease since appearance of IgM antibodies usually occur after fifth day of the infection. The studies showed high level of expression in case of constructed vector as compared to infected virus for the specific protein. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639731/ doi: 10.1007/s13337-011-0027-2 id: cord-014597-66vd2mdu author: nan title: Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017 date: 2018-03-15 words: 50613.0 sentences: 2624.0 pages: flesch: 46.0 cache: ./cache/cord-014597-66vd2mdu.txt txt: ./txt/cord-014597-66vd2mdu.txt summary: Irrespective of the cell culture-based system and production scale, PEIpro® and PEIpro®-HQ have led to efficient viral vector yields superior to 10 7 IG/mL and 10 9 VG/mL, respectively for lentiviruses and AAVs Background Continuous perfusion process is making a comeback as a competing upstream manufacturing technology for the production of Biopharmaceuticals compared to the standard fed batch processes. To evaluate the impact of feed-spiking compared with cultivation in basal medium only, the cell line was grown in bioreactors under controlled conditions to determine cellspecific metabolic rates, nutrient consumption, and byproduct accumulation over the process time. Through the interchangeability of signal peptides between products and even species, a large variety can be used to enhance protein expression in already existing production systems Materials and methods At first the influence of four different natural SPs (SP (7), (8), (9) and (10)) was compared on the secreted amount of an IgG4 model antibody (product A) in fed batches using a CHO DG44 host cell line. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861492/ doi: 10.1186/s12919-018-0097-x id: cord-014685-ihh30q6f author: nan title: Posters P788 - P999 date: 2005-09-21 words: 38354.0 sentences: 1784.0 pages: flesch: 45.0 cache: ./cache/cord-014685-ihh30q6f.txt txt: ./txt/cord-014685-ihh30q6f.txt summary: This study has attempted to analyse the structural properties of membrane peptides and proteins through the use of model systems that have been designed to mimic their natural counterparts: Podlubnaya 2 1 Institute of Theoretical and Experimental Biophysics RAS, 2 Pushchino State University Amyloid brils are formed by proteins or their peptides in the result of a conformational transition from alpha helix into beta-sheet structure. Analysis of the results of such studies indicate that folding of SNase fragments is dominated by developing the local and non-local nucleation sites from native-like secondary structures and by intensifying the longrange interactions of residues at nucleation sites with residues further removed in sequence. The results show that at different pH values the aggregation processes of both proteins follow different pathways determined by the variations in the native structure and by the details of the involved conformational changes. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080055/ doi: 10.1007/s00249-005-0504-x id: cord-014864-0d682m0n author: nan title: Biomedical vignette date: 2008-10-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089141/ doi: 10.1007/s11373-008-9279-2 id: cord-020097-eh5deunk author: nan title: Cumulative Author Index for 2006 (Volumes 115–122) date: 2006-10-27 words: 1481.0 sentences: 87.0 pages: flesch: 28.0 cache: ./cache/cord-020097-eh5deunk.txt txt: ./txt/cord-020097-eh5deunk.txt summary: Modulation of PKR activity in cells infected by bovine viral diarrhea virus Complete genome analysis of RFLP 184 isolates of porcine reproductive and respiratory syndrome virus Phylogenetic analysis of the gag region encoding the matrix protein of small ruminant lentiviruses: Comparative analysis and molecular epidemiological applications TATAbinding protein and TBP-associated factors during herpes simplex virus type 1 infection: Localization at viral DNA replication sites Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein Efficient inhibition of hepatitis B virus replication by small interfering RNAs targeted to the viral X gene in mice Preparation and characterization of a novel monoclonal antibody specific to severe acute respiratory syndrome-coronavirus nucleocapsid protein A deletion and point mutation study of the human papillomavirus type 16 major capsid gene Sequencing and comparative analysis of a pig bovine viral diarrhea virus genome Antigenic structure analysis of glycosylated protein 3 of porcine reproductive and respiratory syndrome virus abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134138/ doi: 10.1016/s0168-1702(06)00318-2 id: cord-020101-5rib7pe8 author: nan title: Cumulative Author Index for 2008 date: 2008-11-17 words: 2140.0 sentences: 126.0 pages: flesch: 29.0 cache: ./cache/cord-020101-5rib7pe8.txt txt: ./txt/cord-020101-5rib7pe8.txt summary: Cauliflower mosaic virus gene VI product N-terminus contains regions involved in resistance-breakage, self-association and interactions with movement protein Intrahost evolution of envelope glycoprotein and OrfA sequences after experimental infection of cats with a molecular clone and a biological isolate of feline immunodeficiency virus DC-SIGN enhances infection of cells with glycosylated West Nile virus in vitro and virus replication in human dendritic cells induces production of Increase in proto-oncogene mRNA transcript levels in bovine lymphoid cells infected with a cytopathic type 2 bovine viral diarrhea virus Complete genome sequence analysis of dengue virus type 2 isolated in Modulation of hepatitis B virus replication by expression of polymerasesurface fusion protein through splicing: Implications for viral persistence Induction of apoptosis in Vero cells by Newcastle disease virus requires viral replication, de-novo protein synthesis and caspase activation Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134142/ doi: 10.1016/s0168-1702(08)00367-5 id: cord-020235-stcrozdw author: nan title: Abstracts of Papers Presented at the 38th Meeting of the Deutsche Gesellschaft für Hygiene und Mikrobiologie, Virology Section, Göttingen, 5.–8.10.1981 date: 2012-03-15 words: 13494.0 sentences: 843.0 pages: flesch: 58.0 cache: ./cache/cord-020235-stcrozdw.txt txt: ./txt/cord-020235-stcrozdw.txt summary: Hepatitis A virus (HAV) was isolated directly from human stool in diploid human fibroplasrs, Viral antigen was expressed only after 210 days of incubation of the infected cultures. Univ., 0-8700 Wiirzburg Effect of Measles (SSPE) Antiserum on Viral Surface Proteins and Hormone Receptor Activity in C6/SSPE Persistently Infected Cells BARRETT, P. Inst, of Genetics, Univ., 0-5000 Co logne Virus-Cell DNA Recombinants in Human Cells Lytically Infected by Ad2 NEUMANN, R., WEYER, U., and DOERFLER, W. In vitro, however, the gag-specific peptide sequences are cleaved off upon addition of the purified viral piS protease; in the case of the replication-defective, transforming avian sarcoma virus PRC II the cleaved nongag part has a ryrosine-phosphorylaring kinase activity similar to that described for the RSV src-gene product pp60 src . f. Virologie, Univ., D·6300 Giefen, 3 A protein of a molecular weight of about 38.000 d has been found to be phosphorylated 1 h after the onset of cell transformation by Rous sarcoma virus (RSV). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134445/ doi: 10.1016/s0174-3031(82)80128-5 id: cord-022779-himray6q author: nan title: Abstracts of oral presentations date: 2005-06-10 words: 3621.0 sentences: 164.0 pages: flesch: 41.0 cache: ./cache/cord-022779-himray6q.txt txt: ./txt/cord-022779-himray6q.txt summary: Here we present a novel strategy to synthesize proteins through a chemical ligation using unprotected peptide segments. Using short portions (7-11 amino acid) rich in positively charged residues from either human lactoferricin or the MARCKS protein as templates, a panel of 70 peptides each possessing a specific chemical structure was synthesized. Subsequent functionalization of such azide groups via Staudinger or "Click" chemistry should provide a convenient method for linking proteins with a diverse array of probes, biomolecules, surfaces and other materials under mild conditions. Moreover, the advantages of peptide and protein chemical synthesis over recombinant-DNA methods are increasingly being used to provide rapid structure-activity information of complex bioactive peptides, small proteins and functional receptor domains. Thus, these new peptides bear all of the requirements which are necessary for formation of cooperatively interacting helical structures and, furthermore, contain domains for cooperative sheet aggregation as well. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161772/ doi: 10.1002/bip.20321 id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 words: 188640.0 sentences: 9313.0 pages: flesch: 45.0 cache: ./cache/cord-022888-dnsdg04n.txt txt: ./txt/cord-022888-dnsdg04n.txt summary: Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. abstract: No Abtract url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163517/ doi: 10.1002/eji.200990224 id: cord-022940-atbjwpo5 author: nan title: Poster Sessions date: 2016-09-07 words: 241182.0 sentences: 12746.0 pages: flesch: 47.0 cache: ./cache/cord-022940-atbjwpo5.txt txt: ./txt/cord-022940-atbjwpo5.txt summary: We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164006/ doi: 10.1111/febs.13808 id: cord-022955-vy0qgtll author: nan title: Proteases date: 2005-06-20 words: 36388.0 sentences: 1759.0 pages: flesch: 43.0 cache: ./cache/cord-022955-vy0qgtll.txt txt: ./txt/cord-022955-vy0qgtll.txt summary: In order to understand the molecular basis of the enzyme-substrate binding mechanism, we employ the synthetic peptide and mass spectrometry-based approaches to investigate the significance of selected amino acid residues that are flanking both sides of the SARS-CoV 3CL pro cleavage site. To contribute to the assignment of a physiological role to genomic-derived peptidases and to make them more accessible for the drug discovery process, we have undertaken a program consisting of mRNA expression profiling, full-length recombinant expression in insect cells, purification and determination of the catalytic activity for the human proteolytic enzymes. This comprehensive analysis of the local backbone properties of SGTI in the free and in the complex form made possible to identify conformational similarities and differences responsible for its efficient binding to the enzyme, and provides a good basis for further studying the structural aspects of protease inhibitor specificity. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164095/ doi: 10.1111/j.1742-4658.2005.4739_4.x id: cord-023026-2r84ndzv author: nan title: Posters date: 2013-06-14 words: 138458.0 sentences: 6513.0 pages: flesch: 40.0 cache: ./cache/cord-023026-2r84ndzv.txt txt: ./txt/cord-023026-2r84ndzv.txt summary: Thus, this work provides the basis to identify molecular pathways regulated by distinct niche/environmental signals and involved in the heterogeneity of adult OPCs. Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS) characterized by inflammation, which leads to formation of demyelinating areas due to loss of oligodendrocytes, astrogliosis and, finally, axonal degeneration. Taken together, these results demonstrate the important role of miR-200b in modulating the MAPK pathway via c-Jun which in turn affects different aspects of the inflammatory process accompanying microglia activation including cytokine response, NO production, phagocytosis and neuronal cell death. For this purpose, coronal cryostat free-floating sections from the brain of both adult transgenic mice and their corresponding wild-type (Wt) littermates, were processed for the study of astrocytes using GFAP immunohistochemistry and microglia using antibodies against Iba1 and several markers commonly related to the activated phenotype of these microglial cells, such as CD16/32 (Fc receptor), F4/80, CD11b, CD206, CD150 and MHC-II. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165910/ doi: 10.1002/glia.22530 id: cord-023143-fcno330z author: nan title: Molecular aspects of viral immunity date: 2004-02-19 words: 43425.0 sentences: 2056.0 pages: flesch: 47.0 cache: ./cache/cord-023143-fcno330z.txt txt: ./txt/cord-023143-fcno330z.txt summary: Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167094/ doi: 10.1002/jcb.240591009 id: cord-023208-w99gc5nx author: nan title: Poster Presentation Abstracts date: 2006-09-01 words: 70854.0 sentences: 3492.0 pages: flesch: 43.0 cache: ./cache/cord-023208-w99gc5nx.txt txt: ./txt/cord-023208-w99gc5nx.txt summary: In order to develop a synthetic protocol by an automated instrumentation, increasing yield, purity of the crude, and reaction time, a microwave-assisted solid phase peptide synthesis was validated comparing the use of the new generation of Triazine-Based Coupling Reagents (TBCRs) with a series of commonly used ones. Ubiquitinium is a well known mechanism in protein degredation of Eukaryotic cells ,in which many obsolte and corrupted three dimentional structure protein ,become marked by covalent attachment of ubuquitin through a multi-step enzymatic pathway.Ubiquitin is a small ,8.5 kDa peptide of 76 amino acid residues that targets such substrtes for proteolysis in proteasome .Recnt studies showed that an extra cellular ubiquitination process also taking place in the epididymes of humans and other animals marks protein on the surface of the defective sperm .it appears that structurally and functionally defective sperm become surface ubiquitinated by epididymal epithelial cells. This head-to-tailcyclized 14-amino-acid peptide contains one disulfide bridge and a lysine residue (Lys5) present in the P1 position, which is responsible for inhibitor specificity.As was reported by us and other groups, SFTI-1 analogues with one cycle only retain trypsin inhibitory activity. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167816/ doi: 10.1002/psc.797 id: cord-023209-un2ysc2v author: nan title: Poster Presentations date: 2008-10-07 words: 111878.0 sentences: 5398.0 pages: flesch: 45.0 cache: ./cache/cord-023209-un2ysc2v.txt txt: ./txt/cord-023209-un2ysc2v.txt summary: Site-specifi c PEGylation of human IgG1-Fab using a rationally designed trypsin variant In the present contribution we report on a novel, highly selective biocatalytic method enabling C-terminal modifi cations of proteins with artifi cial functionalities under native state conditions. Recently, our group report a novel approach to a totally synthetic vaccine which consists of FMDV (Foot and Mouth Disease Virus) VP1 peptides, prepared by covalent conjugation of peptide biomolecules with membrane active carbochain polyelectrolytes In the present study, peptide epitops of VP1 protein both 135-161(P1) amino acid residues (Ser-Lys-Tyr-Ser-Thr-Thr-Gly-Glu-Arg-Thr-Arg-Thr-Arg-Gly-Asp-Leu-Gly-Ala-Leu-Ala-Ala-Arg-Val-Ala-Thr-Gln-Leu-Pro-Ala) and triptophan (Trp) containing on the N terminus 135-161 amino acid residues (Trp-135-161) (P2) were synthesized by using the microwave assisted solid-phase methods. Using as a template a peptide, already identifi ed, with agonist activity against PTPRJ(H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), here we report a structure-activity study carried out through endocyclic modifi cations (Ala-scan, D-substitutions, single residue deletions, substitutions of the disulfi de bridge) and the preliminary biological results of this set of compounds. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167823/ doi: 10.1002/psc.1090 id: cord-023225-5quigar4 author: nan title: Posters date: 2012-08-21 words: 70251.0 sentences: 3367.0 pages: flesch: 43.0 cache: ./cache/cord-023225-5quigar4.txt txt: ./txt/cord-023225-5quigar4.txt summary: To further explore the structure-function relationship, a viable synthesis strategy for pseudodesmin A analogues was developed, based on side-chain attachment of the first amino acid to the solid support, followed by stepwise Fmoc solid-phase synthesis of the linear peptide precursor and on-resin head-to-tail cyclization. The cases when the amino acid sequence of a fragment coincided with part of the primary structure of a natural oligopeptide were recorded in the Total protein chemical synthesis requires a case by case design and optimization which is governed by factors such as the solubility of the individual peptide segments, their primary sequence and in particular the presence of "difficult" amino acid residues at ligation junctions such as proline or the location of cysteines. In this study we present synthesis of two series of peptide libraries, which were designed by substitution of Leu in the P5, P6 position of our control peptide (Ac-LLLLRVKR-AMBA) with each of nineteen amino acid residues in order to verifying its influence on activity and selectivity of the resulting analogues. abstract: No abstract is available for this article. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167970/ doi: 10.1002/psc.2449 id: cord-023647-dlqs8ay9 author: nan title: Sequences and topology date: 2003-03-21 words: 4505.0 sentences: 747.0 pages: flesch: 69.0 cache: ./cache/cord-023647-dlqs8ay9.txt txt: ./txt/cord-023647-dlqs8ay9.txt summary: Nucleotide Sequence Analysis of the L G~ne of Vesicular Stomafltia Virus (New Jersey Serotype) --Identification of Conserved Domai~L~ in L Proteins of Nonsegmented Negative-Strand RNA Viruses DERSE I~ Equine Infectious Anemia Virus tat--Insights into the Structure, Function, and Evolution of Lentivtrus tran.~Activator Proteins Ho~tu~ ~ s71 is a Ehylngcueticellly Distinct Human Endogenous Reteovtgal 1Rlement with Structural mad Sequence Homology to Simian Sarcoma Virus (SSV). Distinct Fercedoxins from Rhodobacter-Capsulstus -Complete Amino Acid Sequences and Molecular Evolution Complete Amino Acid Sequence and Homologies of Human Erythrocyte Membrane Protein Band 4.2. Identification of Two Highly Conserved Amino Acid Sequences Amon~ the ~x-subunits and Molecular ~ The Predicted Amino Acid Sequence of ct-lnternexin is that of a novel Neuronal lntegmedla~ ~ent Protein Inttaspecific Evolution of a Gene Family Coding for Urinary Proteins Attalysi~ of CDNA for Human ~ AJudgyrin I~dicltes a Repeated Structure with Homology to Tissue-Differentiation a~td Cell-Cycle Control Protein abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173161/ doi: 10.1016/0959-440x(91)90051-t id: cord-023770-ymxapsv6 author: nan title: Closteroviridae date: 2011-11-23 words: 3662.0 sentences: 197.0 pages: flesch: 53.0 cache: ./cache/cord-023770-ymxapsv6.txt txt: ./txt/cord-023770-ymxapsv6.txt summary: In general, capsid proteins and their homologs (CPm) show a significant degree of sequence conservation and the duplicate copies probably retain the general spatial folding and some crucial properties of the CPs. Notable exception are a group of ampeloviruses with the smallest genomes in the family [e.g. grapevine leafrollassociated virus 4 (GLRaV-4), GLRaV-5, GLRaV-6, GLRaV-9, pineapple mealybug wilt-associated virus 1(PMWaV-1) and PMWaV-3] which do not appear to possess CPm. The genome expression strategy is based on: (i) proteolytic processing of the polyprotein encoded by ORF1a; (ii) 1 Pos. ssRNA ribosomal frameshift for the expression of the RdRp domain encoded by ORF1b, a mechanism not found in other ()RNA plant viruses; (iii) expression of the downstream ORFs via the formation of a nested set of 3 co-terminal sub-genomic RNAs (sgRNAs). abstract: This chapter focuses on Closteroviridae family whose member genuses are Closterovirus, Ampelovirus, and Crinivirus. The virions are helically constructed filaments with a pitch of the primary helix in the range of 3.4–3.8 nm, containing about 10 protein subunits per turn of the helix and showing a central hole of 3–4 nm. The very flexuous and open structure of the particles is the most conspicuous trait of members of the family. The virions have a diameter of about 12 nm and their length ranges from 650 nm in case of species with fragmented genome, to over 2000 nm in case of species with monopartite genome. The fragility of virions and a tendency to end-to-end aggregation contribute to the fact that a range of lengths is often given for single viruses. The virions of several species are degraded by CsCl and are unstable in high salt concentration, resist moderately high temperatures and organic solvents, but are sensitive to RNase and chelation. Regardless of the genome type, monopartite or fragmented, virions contain a single molecule of linear, positive sense, single stranded RNA, constituting 5–6% of the particle weight. The structural proteins of most members of the family consist of a major CP and of a diverged copy of it denoted minor CP (CPm), with a size ranging from 22 to 46 kDa (CP) and 23 to 80 kDa (CPm). The members of the family have one of the largest genomes among plant viruses because of sequence duplication and acquisition of nonviral coding sequences such as protease, and HSP70 protein via RNA recombination. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173617/ doi: 10.1016/b978-0-12-384684-6.00085-9 id: cord-031907-ilhr3iu5 author: nan title: ISEV2020 Abstract Book date: 2020-07-15 words: 200999.0 sentences: 11528.0 pages: flesch: 44.0 cache: ./cache/cord-031907-ilhr3iu5.txt txt: ./txt/cord-031907-ilhr3iu5.txt summary: L.M., and the National Institutes of Health (R35GM119623) to T.R.G. The addition of a size exclusion chromatography step to various urinary extracellular vesicle concentrating methods reveals differences in the small RNA profile Introduction: Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases, however non-vesicular RNA (e.g. associated with proteins) is also present within urine. We then evaluated efficiency of heart targeting for eAAV9 or eAAV6 and standard AAV9 or AAV6 encoding for EGFP, mCherry or firefly luciferase in different human cell lines in vitro, in black mouse and in passive immunity nude mouse model in vivo using flow cytometry, confocal microscopy, Langendorff perfusion system and Methods: HLHS patients (n = 3) after Glenn procedure and swine (n = 3) after PAB were given RV injections of allogeneic/xenogeneic MSCs. Donor-specific, HLA-I+, exosomes were isolated from plasma. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480431/ doi: 10.1080/20013078.2020.1784511 id: cord-104279-choywmwd author: nan title: Membrane protein sorting in the yeast secretory pathway: evidence that the vacuole may be the default compartment date: 1992-10-01 words: 9856.0 sentences: 411.0 pages: flesch: 52.0 cache: ./cache/cord-104279-choywmwd.txt txt: ./txt/cord-104279-choywmwd.txt summary: First, to determine if the lumenal domain was sorted to the vacuole when expressed in the secretory pathway as a soluble protein, a gene fusion was used to create the protein ctFss-B, consisting of the NH2-terminal ER-targeting signal sequence of prepro-t~ factor fused to the lumenal domain of DPAP B at residue 49 ( Fig. 1 B) . To ad-dress the possibility that the mutant constructs analyzed in this study were mislocalized to the plasma membrane followed by rapid endocytic uptake to the vacuole, indirect immunofluorescence experiments were performed on BB-Inv, B-A-B, A20-BB, and/x22-AA-B expressed in a secl strain at 34~ As a positive control for accumulation in secretory vesicles, the localization of the fusion protein Fusl-LacZp was analyzed (Trueheart et al., 1987) . abstract: The targeting signals of two yeast integral membrane dipeptidyl aminopeptidases (DPAPs), DPAP B and DPAP A, which reside in the vacuole and the Golgi apparatus, respectively, were analyzed. No single domain of DPAP B is required for delivery to the vacuolar membrane, because removal or replacement of either the cytoplasmic, transmembrane, or lumenal domain did not affect the protein's transport to the vacuole. DPAP A was localized by indirect immunofluorescence to non-vacuolar, punctate structures characteristic of the yeast Golgi apparatus. The 118-amino acid cytoplasmic domain of DPAP A is sufficient for retention of the protein in these structures, since replacement of the cytoplasmic domain of DPAP B with that of DPAP A resulted in an immunolocalization pattern indistinguishable from that of wild type DPAP A. Overproduction of DPAP A resulted in its mislocalization to the vacuole, because cells expressing high levels of DPAP A exhibited vacuolar as well as Golgi staining. Deletion of 22 residues of the DPAP A cytoplasmic domain resulted in mislocalization of the mutant protein to the vacuole. Thus, the cytoplasmic domain of DPAP A is both necessary and sufficient for Golgi retention, and removal of the retention signal, or saturation of the retention apparatus by overproducing DPAP A, resulted in transport to the vacuole. Like wild type DPAP B, the delivery of mutant membrane proteins to the vacuole was unaffected in the secretory vesicle-blocked sec1 mutant; thus, transport to the vacuole was not via the plasma membrane followed by endocytosis. These data are consistent with a model in which membrane proteins are delivered to the vacuole along a default pathway. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2289628/ doi: nan id: cord-104282-90t1m430 author: nan title: Microsomal aldehyde dehydrogenase is localized to the endoplasmic reticulum via its carboxyl-terminal 35 amino acids date: 1994-09-02 words: 7076.0 sentences: 394.0 pages: flesch: 53.0 cache: ./cache/cord-104282-90t1m430.txt txt: ./txt/cord-104282-90t1m430.txt summary: Abbreviations used in this paper: CAT, chloramphenicol acetyltransferase; FP2, NADPH-cytochrome P-450 reductase; msALDH, microsomal aldehyde dehydrogenase; PBS(+), PBS containing 1 mM CaCI2 and 0.5 mM MgCI2; PDI, protein disulfide isomerase; PTP, protein tyrosine phosphatase; STE, sucrose solution containing 10 mM Tris-HCl, pH 7.4, 1 mM EDTA, 10 t~g/ml leupepdn A, 0.5 mM PMSF, and 10 U/ml Trasyol; SRP, signal recognition particle. The nucleotide sequence predicts a polypeptide of 484 amino acids, and the most characteristic feature of this membrane-bound ALDH is carboxyl-terminal 35 amino acids, consisting of a stem region (amino acids 450-463) and a hydrophobic domain (amino acids 464-480) followed by a short hydrophilic tail region (amino acids 481-484) as shown in Fig. 1 . These data, together with those from subcellular fractionation, suggested that the carboxyl-terminal portion of msALDH including the hydrophobic sequence (amino acid 464-480) was necessary for both its ER localization and the tight association with the ER membrane. abstract: Rat microsomal aldehyde dehydrogenase (msALDH) has no amino-terminal signal sequence, but instead it has a characteristic hydrophobic domain at the carboxyl terminus (Miyauchi, K., R. Masaki, S. Taketani, A. Yamamoto, A. Akayama, and Y. Tashiro. 1991. J. Biol. Chem. 266:19536- 19542). This membrane-bound enzyme is a useful model protein for studying posttranslational localization to its final destination. When expressed from cDNA in COS-1 cells, wild-type msALDH is localized exclusively in the well-developed ER. The removal of the hydrophobic domain results in the cytosolic localization of truncated proteins, thus suggesting that the portion is responsible for membrane anchoring. The last 35 amino acids of msALDH, including the hydrophobic domain, are sufficient for targeting of E. coli beta-galactosidase to the ER membrane. Further studies using chloramphenicol acetyltransferase fusion proteins suggest that two hydrophilic sequences on either side of the hydrophobic domain play an important role in ER targeting. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2290952/ doi: nan id: cord-289710-ucguzgdm author: nan title: Yeast Kex1p is a Golgi-associated membrane protein: deletions in a cytoplasmic targeting domain result in mislocalization to the vacuolar membrane date: 1992-12-02 words: 7986.0 sentences: 376.0 pages: flesch: 51.0 cache: ./cache/cord-289710-ucguzgdm.txt txt: ./txt/cord-289710-ucguzgdm.txt summary: In addition to soluble proteins, the cell surface appears to be the default destination for mammalian ER, Golgi, and lysosomal membrane proteins as removal of their respective retention/targeting signals results in their delivery to the plasma membrane (Machamer and Rose, 1987; Jackson et al., 1990; Williams and Fukuda, 1990) . Kexlp is predicted to be a type I transmembrane protein with a large amino-terminal protease domain in the lumen of the secretory pathway, a single membrane-spanning domain, and a smaller carboxy-terminai domain positioned cytoplasmicaUy. The observation that KEX/cells intracellularly retain Kexlp activity prompted an analysis to determine in which secretory compartment Kexlp resided, and how it achieved such retention. The above results indicated that Kexlp-Hpa was membrane associated, had received glycosyl modifications in the Golgi apparatus, gave wild-type levels of total activity, and was retained intracellularly; yet processed the K1 killer toxin precursor to a lesser extent than Kexlp. abstract: We have investigated the localization of Kex1p, a type I transmembrane carboxypeptidase involved in precursor processing within the yeast secretory pathway. Indirect immunofluorescence demonstrated the presence of Kex1p in a punctate organelle resembling the yeast Golgi apparatus as identified by Kex2p and Sec7p (Franzusoff, A., K. Redding, J. Crosby, R. S. Fuller, and R. Schekman. 1991. J. Cell Biol. 112:27- 37). Glycosylation studies of Kex1p were consistent with a Golgi location, as Kex1p was progressively N-glycosylated in an MNN1- dependent manner. To address the basis of Kex1p targeting to the Golgi apparatus, we examined the cellular location of a series of carboxy- terminal truncations of the protein. The results indicate that a cytoplasmically exposed carboxy-terminal domain is required for retention of this membrane protein within the Golgi apparatus. Deletions of the retention region or overproduction of wild-type Kex1p led to mislocalization of Kex1p to the vacuolar membrane. This unexpected finding is discussed in terms of models involving either the vacuole as a default destination for membrane proteins, or by endocytosis to the vacuole following their default localization to the plasma membrane. url: https://www.ncbi.nlm.nih.gov/pubmed/1469044/ doi: nan id: cord-300796-rmjv56ia author: nan title: The signal sequence of the p62 protein of Semliki Forest virus is involved in initiation but not in completing chain translocation date: 1990-09-01 words: 8031.0 sentences: 405.0 pages: flesch: 57.0 cache: ./cache/cord-300796-rmjv56ia.txt txt: ./txt/cord-300796-rmjv56ia.txt summary: In this work we show that the p62 protein of Semliki Forest virus contains an uncleaved signal sequence at its NH2-terminus and that this becomes glycosylated early during synthesis and translocation of the p62 polypeptide. As the glycosylation of the signal sequence most likely occurs after its release from the ER membrane our results suggest that this region has no role in completing the transfer process. Furthermore, the p62-reporter hybrid should be translocated across microsomal membranes and possibly glycosylated at Asn~3 of the p62 sequence if the 40 residues long NH2-terminal p62 peptide carries a signal sequence. This must involve Asn~3 of the p62 peptide as it is part of the only potential glycosylation site on the hybrid polypeptides (Garoff et al., 1980 ; references on dhfr sequence in legend to Fig. 1) , Finally, we can also conclude that the p62 signal sequence does not provide a stable membrane anchor to the translocated chain. abstract: So far it has been demonstrated that the signal sequence of proteins which are made at the ER functions both at the level of protein targeting to the ER and in initiation of chain translocation across the ER membrane. However, its possible role in completing the process of chain transfer (see Singer, S. J., P. A. Maher, and M. P. Yaffe. Proc. Natl. Acad. Sci. USA. 1987. 84:1015-1019) has remained elusive. In this work we show that the p62 protein of Semliki Forest virus contains an uncleaved signal sequence at its NH2-terminus and that this becomes glycosylated early during synthesis and translocation of the p62 polypeptide. As the glycosylation of the signal sequence most likely occurs after its release from the ER membrane our results suggest that this region has no role in completing the transfer process. url: https://www.ncbi.nlm.nih.gov/pubmed/2391367/ doi: nan id: cord-327883-s9nbr5y8 author: nan title: Section Virology date: 1990-03-31 words: 10576.0 sentences: 571.0 pages: flesch: 48.0 cache: ./cache/cord-327883-s9nbr5y8.txt txt: ./txt/cord-327883-s9nbr5y8.txt summary: By improving the enzyme-linked immunosorbent assay (ELISA) for HSV-2-antibodies and additional testing of sera by Western blot, we were able to specifically identify HSV-l-and HSV-2-antibodies in serum samples. To get some insight into the molecular basis of processes controlling the viral expression we studied the sequence-specific DNA-protein interactions within the genomic regulatory regions. for Med. Microbiology, Univ., D-5300 Bonn Semiquantitative detection of Hepatitis B Virus (HBV) DNA in sera of infected individuals has become an important means of modern serological hepatitis diagnostics. THOMSSEN 1 In the course of acute Epstein-Barr virus (EBV) infection IgM antibodies always occur against two cellular antigens that were characterized as proteins with a molecular weight of 26 kD (p26) and 29 kD (p29), respectively. The frequency and specificity of antibodies to P-gene encoded proteins of human hepatitis B virus was tested in sera of acute and chronically infected patients with and without hepatocellular carcinoma (HCC). abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0934884011800393 doi: 10.1016/s0934-8840(11)80039-3 id: cord-306261-yc2y2xak author: van Tricht, Ewoud title: Fast, selective and quantitative protein profiling of adenovirus-vector based vaccines by ultra-performance liquid chromatography date: 2018-12-28 words: 5810.0 sentences: 275.0 pages: flesch: 47.0 cache: ./cache/cord-306261-yc2y2xak.txt txt: ./txt/cord-306261-yc2y2xak.txt summary: The new RP-UPLC method was successfully validated for protein profiling and relative quantification of proteins in vaccine products based on adenovirus vector types 26 and 35. By calculating the relative peak areas of all peaks in the chromatogram and identifying new peaks in the chromatogram, the method also allows the detections of degradation products in the sample Additional requirements for the method development were: a chromatographic run time of less than 30 min, baseline separation of all relevant adenovirus proteins allowing for their quantification, and an increased method robustness. The linear gradient with three slopes was replaced by a single-slope linear gradient to improve elution reproducibility and the flow rate was increased The critical method parameters of the RP-UPLC method were studied in a screening design of experiments to assess their impact on the method''s run time and the resolution between the adenovirus proteins.: The following conditions were evaluated: gradient start composition (0-20% solvent B), gradient end composition (45-65% solvent B), gradient run time (17-25 min), TFA concentration (0.04-0.12%), and column temperature (40-70 • C). abstract: Abstract A method for the quantitative determination of the protein composition of adenovirus-vector based vaccines was developed. The final method used RP-UPLC with UV absorbance detection, a C4 column (300 Å, 1.7 μm, 2.1 × 150 mm), and a water- acetonitrile (ACN) gradient containing trifluoroacetic acid (TFA) as ion-pairing agent. The chromatographic resolution between the various adenovirus proteins was optimized by studying the effect of the TFA concentration and the column temperature, applying a full factorial design of experiments. A reproducible baseline separation of all relevant adenovirus proteins could be achieved within 17 min run time. Samples containing adenovirus particles could be directly injected into the UPLC system without sample pretreatment. The viruses reproducibly dissociate into proteins in the UPLC system upon contact with the mobile phase containing ACN. The new RP-UPLC method was successfully validated for protein profiling and relative quantification of proteins in vaccine products based on adenovirus vector types 26 and 35. The intermediate precision of the relative peak areas of all proteins was between 1% and 14% RSD, except for the peak assigned to protein V (26% RSD). The method proved to be stability indicating with respect to thermal and oxidation stress of the adenovirus-vector based vaccine and was successfully implemented for the characterization of adenovirus-based products. url: https://www.ncbi.nlm.nih.gov/pubmed/30389208/ doi: 10.1016/j.chroma.2018.10.045 id: cord-355377-b0rcg3rt author: van der Vlag, R. title: Analytical Methods in Protein-Templated Dynamic Combinatorial Chemistry date: 2017-06-29 words: 9842.0 sentences: 518.0 pages: flesch: 53.0 cache: ./cache/cord-355377-b0rcg3rt.txt txt: ./txt/cord-355377-b0rcg3rt.txt summary: Protein-templated dynamic combinatorial chemistry (DCC) has emerged as a powerful method to identify new inhibitors given that it enables the protein to select its own best binder(s) from a library of interconverting compounds. Both DCLs showed a very clear amplification of acylhydrazones: t-butylphenyl and thiophenyl acylhydrazones 4-5c and 4-5g were amplified in presence of hGST P1-1 and SjGST, Scheme 3 Generation of acylhydrazone-based dynamic combinatorial libraries of (A) aldehydes 4 or 6 and hydrazides 5a-j. The protein concentration can be very low, but 1 H-waterLOGSY 21 can be limited by the exchange kinetics of the reversibly formed protein-ligand complexes and might still suffer from overlapping signals, especially for large DCLs. In 2013, the same group introduced a competition-based 1 H-NMR method to screen binders for human 2-oxoglutarate (2OG)dependent oxygenases. abstract: Protein-templated dynamic combinatorial chemistry (DCC) has emerged as a powerful method to identify new inhibitors given that it enables the protein to select its own best binder(s) from a library of interconverting compounds. Since the first report of DCC applied to the discovery of binders for a protein, this elegant tool has been employed on a range of protein targets in early stage of medicinal-chemistry projects. A toolbox with various reversible and biocompatible reactions has become available, and the portfolio of analytical techniques is growing. Despite progress, in most cases, the libraries employed remain of moderate size due to difficulties associated with their analysis. In this article, analytical methods used in protein-templated DCC are described using examples of recent developments and reports. url: https://www.sciencedirect.com/science/article/pii/B9780124095472125594 doi: 10.1016/b978-0-12-409547-2.12559-4 id: cord-270514-36k9xo7f author: van der Woude, Roosmarijn title: Drivers of recombinant soluble influenza A virus hemagglutinin and neuraminidase expression in mammalian cells date: 2020-08-14 words: 3966.0 sentences: 249.0 pages: flesch: 49.0 cache: ./cache/cord-270514-36k9xo7f.txt txt: ./txt/cord-270514-36k9xo7f.txt summary: Recombinant soluble trimeric influenza A virus hemagglutinins (HA) and tetrameric neuraminidases (NAs) have proven to be excellent tools to decipher biological properties. The two surface envelope proteins of IAV have opposing functions; the trimeric hemagglutinin (HA) binds to sialic acid containing glycans to enable the virus to enter cells, 1,2 the tetrameric neuraminidase (NA) cleaves sialic acids to release new viral particles from the membrane. However, we observed a significant increase in expression yields and determined that it reduced the use of expensive antibodies and provided an excellent handle, as well as an internal read out, of a glycan binding protein. The N-terminal sfGFP increases yields, maintains biological activity, structure and antigenicity, and aids protein quantitation during expression and purification. To determine that sfGFP-NA fusions are enzymatically, antigenically and structurally similar to their non-fused counterparts, we analyzed the GCN4, TB, and sfGFP-TB-N2 proteins with MUNANA and NA specific antibodies (Figure 3 ). abstract: Recombinant soluble trimeric influenza A virus hemagglutinins (HA) and tetrameric neuraminidases (NAs) have proven to be excellent tools to decipher biological properties. Receptor binding and sialic acid cleavage by recombinant proteins correlate satisfactorily compared to whole viruses. Expression of HA and NA can be achieved in a plethora of different laboratory hosts. For immunological and receptor interaction studies however, insect and mammalian cell expressed proteins are preferred due to the presence of N‐linked glycosylation and disulfide bond formation. Because mammalian‐cell expression is widely applied, an increased expression yield is an important goal. Here we report that using codon‐optimized genes and sfGFP fusions, the expression yield of HA can be significantly improved. sfGFP also significantly increased expression yields when fused to the N‐terminus of NA. In this study, a suite of different hemagglutinin and neuraminidase constructs are described, which can be valuable tools to study a wide array of different HAs, NAs and their mutants. url: https://www.ncbi.nlm.nih.gov/pubmed/32710576/ doi: 10.1002/pro.3918 id: cord-309043-dlmx12vt author: von Brunn, Albrecht title: Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome date: 2007-05-23 words: 6706.0 sentences: 341.0 pages: flesch: 52.0 cache: ./cache/cord-309043-dlmx12vt.txt txt: ./txt/cord-309043-dlmx12vt.txt summary: The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. There are reports that a number of MHV and SARS-CoV replicase proteins colocalize and eventually interact in cytoplasmic membrane bound complexes, in which viral RNA synthesis occurs [18, 19] . We therefore cloned the SARS-CoV ORFeome by recombinatorial cloning (GATEWAY technology) and performed a genome-wide analysis for viral protein interactions by yeast-two-hybrid (Y2H) matrix screen. To systematically study the subcellular localization of viral proteins within eukaryotic HeLa cells the SARS-CoV ORFs were transfected in eukaryotic vectors with either N-or C-terminal Flag tags and detected with an anti-Flag antibody. In this study we report the cloning of the complete ORFeome of SARS-CoV and the results of a matrix-based yeast two-hybrid screen of pairwise viral protein-protein interactions. abstract: The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. The functions of a large number of viral ORFs are poorly understood or unknown. In order to gain more insight into functions and modes of action and interaction of the different proteins, we cloned the viral ORFeome and performed a genome-wide analysis for intraviral protein interactions and for intracellular localization. 900 pairwise interactions were tested by yeast-two-hybrid matrix analysis, and more than 65 positive non-redundant interactions, including six self interactions, were identified. About 38% of interactions were subsequently confirmed by CoIP in mammalian cells. Nsp2, nsp8 and ORF9b showed a wide range of interactions with other viral proteins. Nsp8 interacts with replicase proteins nsp2, nsp5, nsp6, nsp7, nsp8, nsp9, nsp12, nsp13 and nsp14, indicating a crucial role as a major player within the replication complex machinery. It was shown by others that nsp8 is essential for viral replication in vitro, whereas nsp2 is not. We show that also accessory protein ORF9b does not play a pivotal role for viral replication, as it can be deleted from the virus displaying normal plaque sizes and growth characteristics in Vero cells. However, it can be expected to be important for the virus-host interplay and for pathogenicity, due to its large number of interactions, by enhancing the global stability of the SARS proteome network, or play some unrealized role in regulating protein-protein interactions. The interactions identified provide valuable material for future studies. url: https://www.ncbi.nlm.nih.gov/pubmed/17520018/ doi: 10.1371/journal.pone.0000459 id: cord-006636-xgikbdns author: Ühlein, E. title: Übersicht Über neue ernährungswissenschaftliche Publikationen date: 1964-02-01 words: 31038.0 sentences: 4914.0 pages: flesch: 58.0 cache: ./cache/cord-006636-xgikbdns.txt txt: ./txt/cord-006636-xgikbdns.txt summary: L. : Effect of a low dietary level of three types of fat on reproductive performance and tissue lipid content of the vitamin B6-deficicnt female rat. H.: Effect of dietary protein and fat on growth, protein utilization, and carcass composition of pigs fed purified diets. Effect of food fats on concentration of ketone bodies and citric acid level in blood and tissues Effect of a low dietary level of three types of fat on reproductive performance and tissue lipid content of the vitamin B6-defieient female rat The effect on the serum cholesterol levels of the consumption of a special dietary fat with a high content of unsaturated fatty acids in elderly people Effect of protein intake and cold exposure on selected liver enzymes associated with amino acid metabolism Effect of protein intake and cold exposure on selected liver enzymes associated with amino acid metabolism abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102153/ doi: 10.1007/bf02021334 ==== 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