Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design
Identifieur interne : 001013 ( Main/Exploration ); précédent : 001012; suivant : 001014Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design
Auteurs : Fenghua Wang [République populaire de Chine] ; Cheng Chen [République populaire de Chine] ; Wenjie Tan [République populaire de Chine] ; Kailin Yang [États-Unis] ; Haitao Yang [République populaire de Chine]Source :
- Scientific Reports [ 2045-2322 ] ; 2016.
Descripteurs français
- KwdFr :
- Antiviraux (isolement et purification), Antiviraux (métabolisme), Conception de médicament, Conformation des protéines, Coronavirus humain NL63 (enzymologie), Cristallographie aux rayons X, Inhibiteurs de protéases (), Inhibiteurs de protéases (métabolisme), Liaison aux protéines, Peptide hydrolases (), Peptide hydrolases (métabolisme), Sites de fixation.
- MESH :
- enzymologie : Coronavirus humain NL63.
- isolement et purification : Antiviraux.
- métabolisme : Antiviraux, Inhibiteurs de protéases, Peptide hydrolases.
- Conception de médicament, Conformation des protéines, Cristallographie aux rayons X, Inhibiteurs de protéases, Liaison aux protéines, Peptide hydrolases, Sites de fixation.
English descriptors
- KwdEn :
- Antiviral Agents (isolation & purification), Antiviral Agents (metabolism), Binding Sites, Coronavirus NL63, Human (enzymology), Crystallography, X-Ray, Drug Design, Peptide Hydrolases (chemistry), Peptide Hydrolases (metabolism), Protease Inhibitors (chemistry), Protease Inhibitors (metabolism), Protein Binding, Protein Conformation.
- MESH :
- chemical , chemistry : Peptide Hydrolases, Protease Inhibitors.
- chemical , isolation & purification : Antiviral Agents.
- chemical , metabolism : Antiviral Agents, Peptide Hydrolases, Protease Inhibitors.
- enzymology : Coronavirus NL63, Human.
- Binding Sites, Crystallography, X-Ray, Drug Design, Protein Binding, Protein Conformation.
Abstract
First identified in The Netherlands in 2004, human coronavirus NL63 (HCoV-NL63) was found to cause worldwide infections. Patients infected by HCoV-NL63 are typically young children with upper and lower respiratory tract infection, presenting with symptoms including croup, bronchiolitis and pneumonia. Unfortunately, there are currently no effective antiviral therapy to contain HCoV-NL63 infection. CoV genomes encode an integral viral component, main protease (Mpro), which is essential for viral replication through proteolytic processing of RNA replicase machinery. Due to the sequence and structural conservation among all CoVs, Mpro has been recognized as an attractive molecular target for rational anti-CoV drug design. Here we present the crystal structure of HCoV-NL63 Mpro in complex with a Michael acceptor inhibitor N3. Structural analysis, consistent with biochemical inhibition results, reveals the molecular mechanism of enzyme inhibition at the highly conservative substrate-recognition pocket. We show such molecular target remains unchanged across 30 clinical isolates of HCoV-NL63 strains. Through comparative study with Mpros from other human CoVs (including the deadly SARS-CoV and MERS-CoV) and their related zoonotic CoVs, our structure of HCoV-NL63 Mpro provides critical insight into rational development of wide spectrum antiviral therapeutics to treat infections caused by human CoVs.
The online version of this article (doi:10.1038/srep22677) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1038/srep22677
PubMed: 26948040
PubMed Central: 4780191
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000432
- to stream Pmc, to step Curation: 000432
- to stream Pmc, to step Checkpoint: 000999
- to stream PubMed, to step Corpus: 001222
- to stream PubMed, to step Curation: 001222
- to stream PubMed, to step Checkpoint: 000E91
- to stream Ncbi, to step Merge: 001517
- to stream Ncbi, to step Curation: 001517
- to stream Ncbi, to step Checkpoint: 001517
- to stream Main, to step Merge: 001016
- to stream Main, to step Curation: 001013
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design</title><author><name sortKey="Wang, Fenghua" sort="Wang, Fenghua" uniqKey="Wang F" first="Fenghua" last="Wang">Fenghua Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.33763.32</institution-id><institution-id institution-id-type="ISNI">0000 0004 1761 2484</institution-id><institution>School of Life Sciences, Tianjin University,</institution></institution-wrap>Tianjin, 300072 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Cheng" sort="Chen, Cheng" uniqKey="Chen C" first="Cheng" last="Chen">Cheng Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.33763.32</institution-id><institution-id institution-id-type="ISNI">0000 0004 1761 2484</institution-id><institution>School of Life Sciences, Tianjin University,</institution></institution-wrap>Tianjin, 300072 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.488175.7</institution-id><institution>Tianjin International Joint Academy of Biotechnology and Medicine,</institution></institution-wrap>Tianjin, 300457 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation></author><author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><affiliation wicri:level="3"><nlm:aff id="Aff3">Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Yang, Kailin" sort="Yang, Kailin" uniqKey="Yang K" first="Kailin" last="Yang">Kailin Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.254293.b</institution-id><institution-id institution-id-type="ISNI">0000 0004 0435 0569</institution-id><institution>Cleveland Clinic Lerner College of Medicine of Case Western Reserve University,</institution></institution-wrap>Cleveland, 44195 OH USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:regionArea>Cleveland</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Haitao" sort="Yang, Haitao" uniqKey="Yang H" first="Haitao" last="Yang">Haitao Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.33763.32</institution-id><institution-id institution-id-type="ISNI">0000 0004 1761 2484</institution-id><institution>School of Life Sciences, Tianjin University,</institution></institution-wrap>Tianjin, 300072 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.488175.7</institution-id><institution>Tianjin International Joint Academy of Biotechnology and Medicine,</institution></institution-wrap>Tianjin, 300457 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26948040</idno><idno type="pmc">4780191</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780191</idno><idno type="RBID">PMC:4780191</idno><idno type="doi">10.1038/srep22677</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000432</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000432</idno><idno type="wicri:Area/Pmc/Curation">000432</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000432</idno><idno type="wicri:Area/Pmc/Checkpoint">000999</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000999</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:26948040</idno><idno type="wicri:Area/PubMed/Corpus">001222</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001222</idno><idno type="wicri:Area/PubMed/Curation">001222</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001222</idno><idno type="wicri:Area/PubMed/Checkpoint">000E91</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000E91</idno><idno type="wicri:Area/Ncbi/Merge">001517</idno><idno type="wicri:Area/Ncbi/Curation">001517</idno><idno type="wicri:Area/Ncbi/Checkpoint">001517</idno><idno type="wicri:Area/Main/Merge">001016</idno><idno type="wicri:Area/Main/Curation">001013</idno><idno type="wicri:Area/Main/Exploration">001013</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design</title><author><name sortKey="Wang, Fenghua" sort="Wang, Fenghua" uniqKey="Wang F" first="Fenghua" last="Wang">Fenghua Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.33763.32</institution-id><institution-id institution-id-type="ISNI">0000 0004 1761 2484</institution-id><institution>School of Life Sciences, Tianjin University,</institution></institution-wrap>Tianjin, 300072 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Cheng" sort="Chen, Cheng" uniqKey="Chen C" first="Cheng" last="Chen">Cheng Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.33763.32</institution-id><institution-id institution-id-type="ISNI">0000 0004 1761 2484</institution-id><institution>School of Life Sciences, Tianjin University,</institution></institution-wrap>Tianjin, 300072 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.488175.7</institution-id><institution>Tianjin International Joint Academy of Biotechnology and Medicine,</institution></institution-wrap>Tianjin, 300457 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation></author><author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><affiliation wicri:level="3"><nlm:aff id="Aff3">Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Yang, Kailin" sort="Yang, Kailin" uniqKey="Yang K" first="Kailin" last="Yang">Kailin Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.254293.b</institution-id><institution-id institution-id-type="ISNI">0000 0004 0435 0569</institution-id><institution>Cleveland Clinic Lerner College of Medicine of Case Western Reserve University,</institution></institution-wrap>Cleveland, 44195 OH USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:regionArea>Cleveland</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Haitao" sort="Yang, Haitao" uniqKey="Yang H" first="Haitao" last="Yang">Haitao Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.33763.32</institution-id><institution-id institution-id-type="ISNI">0000 0004 1761 2484</institution-id><institution>School of Life Sciences, Tianjin University,</institution></institution-wrap>Tianjin, 300072 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.488175.7</institution-id><institution>Tianjin International Joint Academy of Biotechnology and Medicine,</institution></institution-wrap>Tianjin, 300457 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Tianjin</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (isolation & purification)</term><term>Antiviral Agents (metabolism)</term><term>Binding Sites</term><term>Coronavirus NL63, Human (enzymology)</term><term>Crystallography, X-Ray</term><term>Drug Design</term><term>Peptide Hydrolases (chemistry)</term><term>Peptide Hydrolases (metabolism)</term><term>Protease Inhibitors (chemistry)</term><term>Protease Inhibitors (metabolism)</term><term>Protein Binding</term><term>Protein Conformation</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antiviraux (isolement et purification)</term><term>Antiviraux (métabolisme)</term><term>Conception de médicament</term><term>Conformation des protéines</term><term>Coronavirus humain NL63 (enzymologie)</term><term>Cristallographie aux rayons X</term><term>Inhibiteurs de protéases ()</term><term>Inhibiteurs de protéases (métabolisme)</term><term>Liaison aux protéines</term><term>Peptide hydrolases ()</term><term>Peptide hydrolases (métabolisme)</term><term>Sites de fixation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Peptide Hydrolases</term><term>Protease Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antiviral Agents</term><term>Peptide Hydrolases</term><term>Protease Inhibitors</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Coronavirus humain NL63</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Coronavirus NL63, Human</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Antiviraux</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antiviraux</term><term>Inhibiteurs de protéases</term><term>Peptide hydrolases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Crystallography, X-Ray</term><term>Drug Design</term><term>Protein Binding</term><term>Protein Conformation</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Conception de médicament</term><term>Conformation des protéines</term><term>Cristallographie aux rayons X</term><term>Inhibiteurs de protéases</term><term>Liaison aux protéines</term><term>Peptide hydrolases</term><term>Sites de fixation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>First identified in The Netherlands in 2004, human coronavirus NL63 (HCoV-NL63) was found to cause worldwide infections. Patients infected by HCoV-NL63 are typically young children with upper and lower respiratory tract infection, presenting with symptoms including croup, bronchiolitis and pneumonia. Unfortunately, there are currently no effective antiviral therapy to contain HCoV-NL63 infection. CoV genomes encode an integral viral component, main protease (M<sup>pro</sup>), which is essential for viral replication through proteolytic processing of RNA replicase machinery. Due to the sequence and structural conservation among all CoVs, M<sup>pro</sup> has been recognized as an attractive molecular target for rational anti-CoV drug design. Here we present the crystal structure of HCoV-NL63 M<sup>pro</sup> in complex with a Michael acceptor inhibitor N3. Structural analysis, consistent with biochemical inhibition results, reveals the molecular mechanism of enzyme inhibition at the highly conservative substrate-recognition pocket. We show such molecular target remains unchanged across 30 clinical isolates of HCoV-NL63 strains. Through comparative study with M<sup>pro</sup>s from other human CoVs (including the deadly SARS-CoV and MERS-CoV) and their related zoonotic CoVs, our structure of HCoV-NL63 M<sup>pro</sup> provides critical insight into rational development of wide spectrum antiviral therapeutics to treat infections caused by human CoVs.</p><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1038/srep22677) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Weiss, Sr" uniqKey="Weiss S">SR Weiss</name></author><author><name sortKey="Navas Martin, S" uniqKey="Navas Martin S">S Navas-Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masters, Ps" uniqKey="Masters P">PS Masters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Siddell, S" uniqKey="Siddell S">S Siddell</name></author><author><name sortKey="Wege, H" uniqKey="Wege H">H Wege</name></author><author><name sortKey="Ter Meulen, V" uniqKey="Ter Meulen V">V Ter Meulen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weiss, Sr" uniqKey="Weiss S">SR Weiss</name></author><author><name sortKey="Leibowitz, Jl" uniqKey="Leibowitz J">JL Leibowitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ksiazek, Tg" uniqKey="Ksiazek T">TG Ksiazek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuiken, T" uniqKey="Kuiken T">T Kuiken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author><author><name sortKey="Donaldson, Ef" uniqKey="Donaldson E">EF Donaldson</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coleman, Cm" uniqKey="Coleman C">CM Coleman</name></author><author><name sortKey="Frieman, Mb" uniqKey="Frieman M">MB Frieman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Groot, Rj" uniqKey="De Groot R">RJ de Groot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Zumla, Ai" uniqKey="Zumla A">AI Zumla</name></author><author><name sortKey="Al Hakeem, Rf" uniqKey="Al Hakeem R">RF Al-Hakeem</name></author><author><name sortKey="Al Rabeeah, Aa" uniqKey="Al Rabeeah A">AA Al-Rabeeah</name></author><author><name sortKey="Stephens, Gm" uniqKey="Stephens G">GM Stephens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L van der Hoek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vijgen, L" uniqKey="Vijgen L">L Vijgen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drexler, Jf" uniqKey="Drexler J">JF Drexler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ge, Xy" uniqKey="Ge X">XY Ge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, B" uniqKey="He B">B He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Briese, T" uniqKey="Briese T">T Briese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alagaili, An" uniqKey="Alagaili A">AN Alagaili</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Azhar, Ei" uniqKey="Azhar E">EI Azhar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leung, Tf" uniqKey="Leung T">TF Leung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, W" uniqKey="Zhou W">W Zhou</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author><author><name sortKey="Lu, R" uniqKey="Lu R">R Lu</name></author><author><name sortKey="Tan, W" uniqKey="Tan W">W Tan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Owusu, M" uniqKey="Owusu M">M Owusu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matoba, Y" uniqKey="Matoba Y">Y Matoba</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vabret, A" uniqKey="Vabret A">A Vabret</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suzuki, A" uniqKey="Suzuki A">A Suzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bastien, N" uniqKey="Bastien N">N Bastien</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Minosse, C" uniqKey="Minosse C">C Minosse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Forster, J" uniqKey="Forster J">J Forster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Konig, B" uniqKey="Konig B">B Konig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L van der Hoek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K Pyrc</name></author><author><name sortKey="Berkhout, B" uniqKey="Berkhout B">B Berkhout</name></author><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L van der Hoek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fielding, Bc" uniqKey="Fielding B">BC Fielding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, J" uniqKey="Lee J">J Lee</name></author><author><name sortKey="Storch, Ga" uniqKey="Storch G">GA Storch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, X" uniqKey="Yu X">X Yu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoek, Ra" uniqKey="Hoek R">RA Hoek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oosterhof, L" uniqKey="Oosterhof L">L Oosterhof</name></author><author><name sortKey="Christensen, Cb" uniqKey="Christensen C">CB Christensen</name></author><author><name sortKey="Sengelov, H" uniqKey="Sengelov H">H Sengelov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hofmann, H" uniqKey="Hofmann H">H Hofmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K Pyrc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Geng, H" uniqKey="Geng H">H Geng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huynh, J" uniqKey="Huynh J">J Huynh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drexler, Jf" uniqKey="Drexler J">JF Drexler</name></author><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xue, X" uniqKey="Xue X">X Xue</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, H" uniqKey="Yang H">H Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R Hilgenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, H" uniqKey="Yang H">H Yang</name></author><author><name sortKey="Bartlam, M" uniqKey="Bartlam M">M Bartlam</name></author><author><name sortKey="Rao, Z" uniqKey="Rao Z">Z Rao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, H" uniqKey="Yang H">H Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, Q" uniqKey="Zhao Q">Q Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anand, K" uniqKey="Anand K">K Anand</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anand, K" uniqKey="Anand K">K Anand</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J Ziebuhr</name></author><author><name sortKey="Wadhwani, P" uniqKey="Wadhwani P">P Wadhwani</name></author><author><name sortKey="Mesters, Jr" uniqKey="Mesters J">JR Mesters</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R Hilgenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graziano, V" uniqKey="Graziano V">V Graziano</name></author><author><name sortKey="Mcgrath, Wj" uniqKey="Mcgrath W">WJ McGrath</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L Yang</name></author><author><name sortKey="Mangel, Wf" uniqKey="Mangel W">WF Mangel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheng, Sc" uniqKey="Cheng S">SC Cheng</name></author><author><name sortKey="Chang, Gg" uniqKey="Chang G">GG Chang</name></author><author><name sortKey="Chou, Cy" uniqKey="Chou C">CY Chou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, J" uniqKey="Shi J">J Shi</name></author><author><name sortKey="Sivaraman, J" uniqKey="Sivaraman J">J Sivaraman</name></author><author><name sortKey="Song, J" uniqKey="Song J">J Song</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tomar, S" uniqKey="Tomar S">S Tomar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dominguez, Sr" uniqKey="Dominguez S">SR Dominguez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lednicky, Ja" uniqKey="Lednicky J">JA Lednicky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Manns, Mp" uniqKey="Manns M">MP Manns</name></author><author><name sortKey="Von Hahn, T" uniqKey="Von Hahn T">T von Hahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, C" uniqKey="Lin C">C Lin</name></author><author><name sortKey="Kwong, Ad" uniqKey="Kwong A">AD Kwong</name></author><author><name sortKey="Perni, Rb" uniqKey="Perni R">RB Perni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matthews, Da" uniqKey="Matthews D">DA Matthews</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, F" uniqKey="Wang F">F Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Birtley, Jr" uniqKey="Birtley J">JR Birtley</name></author><author><name sortKey="Curry, S" uniqKey="Curry S">S Curry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Otwinowski, Z" uniqKey="Otwinowski Z">Z Otwinowski</name></author><author><name sortKey="Minor, W" uniqKey="Minor W">W Minor</name></author><author><name sortKey="Carter, Cw" uniqKey="Carter C">CW Carter</name></author><author><name sortKey="Sweet, Rm" uniqKey="Sweet R">RM Sweet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccoy, Aj" uniqKey="Mccoy A">AJ McCoy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, P" uniqKey="Emsley P">P Emsley</name></author><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K Cowtan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adams, Pd" uniqKey="Adams P">PD Adams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larkin, Ma" uniqKey="Larkin M">MA Larkin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Robert, X" uniqKey="Robert X">X Robert</name></author><author><name sortKey="Gouet, P" uniqKey="Gouet P">P Gouet</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Ohio</li></region><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Fenghua" sort="Wang, Fenghua" uniqKey="Wang F" first="Fenghua" last="Wang">Fenghua Wang</name></noRegion><name sortKey="Chen, Cheng" sort="Chen, Cheng" uniqKey="Chen C" first="Cheng" last="Chen">Cheng Chen</name><name sortKey="Chen, Cheng" sort="Chen, Cheng" uniqKey="Chen C" first="Cheng" last="Chen">Cheng Chen</name><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><name sortKey="Yang, Haitao" sort="Yang, Haitao" uniqKey="Yang H" first="Haitao" last="Yang">Haitao Yang</name><name sortKey="Yang, Haitao" sort="Yang, Haitao" uniqKey="Yang H" first="Haitao" last="Yang">Haitao Yang</name></country><country name="États-Unis"><region name="Ohio"><name sortKey="Yang, Kailin" sort="Yang, Kailin" uniqKey="Yang K" first="Kailin" last="Yang">Kailin Yang</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001013 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001013 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:4780191
|texte= Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26948040" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |