Serveur d'exploration MERS

Attention, ce site est en cours de développement !
Attention, site généré par des moyens informatiques à partir de corpus bruts.
Les informations ne sont donc pas validées.

A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein

Identifieur interne : 001921 ( Main/Exploration ); précédent : 001920; suivant : 001922

A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein

Auteurs : Yan Li [République populaire de Chine] ; Yuhua Wan [République populaire de Chine] ; Peipei Liu [République populaire de Chine] ; Jincun Zhao [États-Unis] ; Guangwen Lu ; Jianxun Qi [République populaire de Chine] ; Qihui Wang [République populaire de Chine] ; Xuancheng Lu [République populaire de Chine] ; Ying Wu [République populaire de Chine] ; Wenjun Liu [République populaire de Chine] ; Buchang Zhang ; Kwok-Yung Yuen ; Stanley Perlman [États-Unis] ; George F. Gao [République populaire de Chine] ; Jinghua Yan [République populaire de Chine]

Source :

RBID : PMC:4650419

Descripteurs français

English descriptors

Abstract

The newly-emerging Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans. Despite global efforts, the potential for an associated pandemic in the future cannot be excluded. The development of effective counter-measures is urgent. MERS-CoV-specific anti-viral drugs or vaccines are not yet available. Using the spike receptor-binding domain of MERS-CoV (MERS-RBD) to immunize mice, we identified two neutralizing monoclonal antibodies (mAbs) 4C2 and 2E6. Both mAbs potently bind to MERS-RBD and block virus entry in vitro with high efficacy. We further investigated their mechanisms of neutralization by crystallizing the complex between the Fab fragments and the RBD, and solved the structure of the 4C2 Fab/MERS-RBD complex. The structure showed that 4C2 recognizes an epitope that partially overlaps the receptor-binding footprint in MERS-RBD, thereby interfering with the virus/receptor interactions by both steric hindrance and interface-residue competition. 2E6 also blocks receptor binding, and competes with 4C2 for binding to MERS-RBD. Based on the structure, we further humanized 4C2 by preserving only the paratope residues and substituting the remaining amino acids with the counterparts from human immunoglobulins. The humanized 4C2 (4C2h) antibody sustained similar neutralizing activity and biochemical characteristics to the parental mouse antibody. Finally, we showed that 4C2h can significantly abate the virus titers in lungs of Ad5-hCD26-transduced mice infected with MERS-CoV, therefore representing a promising agent for prophylaxis and therapy in clinical settings.


Url:
DOI: 10.1038/cr.2015.113
PubMed: 26391698
PubMed Central: 4650419


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein</title>
<author>
<name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wan, Yuhua" sort="Wan, Yuhua" uniqKey="Wan Y" first="Yuhua" last="Wan">Yuhua Wan</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.252245.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0085 4987</institution-id>
<institution>School of Life Sciences, Anhui University,</institution>
</institution-wrap>
Hefei, 230039 Anhui China</nlm:aff>
<wicri:noCountry code="subfield">230039 Anhui China</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Microbial and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Liu, Peipei" sort="Liu, Peipei" uniqKey="Liu P" first="Peipei" last="Liu">Peipei Liu</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff4">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.214572.7</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1936 8294</institution-id>
<institution>Departments of Microbiology and Pediatrics,</institution>
<institution>University of Iowa,</institution>
</institution-wrap>
Iowa City, 52242 IA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Iowa</region>
</placeName>
<wicri:regionArea>Iowa City</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff11">State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120 Guangdong China</nlm:aff>
<wicri:noCountry code="subfield">510120 Guangdong China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name>
<affiliation>
<nlm:aff id="Aff5">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041 Sichuan China</nlm:aff>
<wicri:noCountry code="subfield">610041 Sichuan China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wang, Qihui" sort="Wang, Qihui" uniqKey="Wang Q" first="Qihui" last="Wang">Qihui Wang</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Microbial and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lu, Xuancheng" sort="Lu, Xuancheng" uniqKey="Lu X" first="Xuancheng" last="Lu">Xuancheng Lu</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff6">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>Laboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC),</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wu, Ying" sort="Wu, Ying" uniqKey="Wu Y" first="Ying" last="Wu">Ying Wu</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Liu, Wenjun" sort="Liu, Wenjun" uniqKey="Liu W" first="Wenjun" last="Liu">Wenjun Liu</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Zhang, Buchang" sort="Zhang, Buchang" uniqKey="Zhang B" first="Buchang" last="Zhang">Buchang Zhang</name>
<affiliation>
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.252245.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0085 4987</institution-id>
<institution>School of Life Sciences, Anhui University,</institution>
</institution-wrap>
Hefei, 230039 Anhui China</nlm:aff>
<wicri:noCountry code="subfield">230039 Anhui China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation>
<nlm:aff id="Aff7">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong,</institution>
</institution-wrap>
Pokfulam, Hong Kong SAR China</nlm:aff>
<wicri:noCountry code="subfield">Hong Kong SAR China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff4">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.214572.7</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1936 8294</institution-id>
<institution>Departments of Microbiology and Pediatrics,</institution>
<institution>University of Iowa,</institution>
</institution-wrap>
Iowa City, 52242 IA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Iowa</region>
</placeName>
<wicri:regionArea>Iowa City</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F" last="Gao">George F. Gao</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.252245.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0085 4987</institution-id>
<institution>School of Life Sciences, Anhui University,</institution>
</institution-wrap>
Hefei, 230039 Anhui China</nlm:aff>
<wicri:noCountry code="subfield">230039 Anhui China</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff8">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC),</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff9">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>China-Japan Joint Laboratory of Molecular Microbiology and Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff10">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC),</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.252245.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0085 4987</institution-id>
<institution>School of Life Sciences, Anhui University,</institution>
</institution-wrap>
Hefei, 230039 Anhui China</nlm:aff>
<wicri:noCountry code="subfield">230039 Anhui China</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Microbial and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">26391698</idno>
<idno type="pmc">4650419</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650419</idno>
<idno type="RBID">PMC:4650419</idno>
<idno type="doi">10.1038/cr.2015.113</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000350</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000350</idno>
<idno type="wicri:Area/Pmc/Curation">000350</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000350</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000F29</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000F29</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="RBID">pubmed:26391698</idno>
<idno type="wicri:Area/PubMed/Corpus">001463</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001463</idno>
<idno type="wicri:Area/PubMed/Curation">001463</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001463</idno>
<idno type="wicri:Area/PubMed/Checkpoint">001660</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001660</idno>
<idno type="wicri:Area/Ncbi/Merge">001274</idno>
<idno type="wicri:Area/Ncbi/Curation">001274</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">001274</idno>
<idno type="wicri:doubleKey">1001-0602:2015:Li Y:a:humanized:neutralizing</idno>
<idno type="wicri:Area/Main/Merge">001926</idno>
<idno type="wicri:Area/Main/Curation">001921</idno>
<idno type="wicri:Area/Main/Exploration">001921</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein</title>
<author>
<name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wan, Yuhua" sort="Wan, Yuhua" uniqKey="Wan Y" first="Yuhua" last="Wan">Yuhua Wan</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.252245.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0085 4987</institution-id>
<institution>School of Life Sciences, Anhui University,</institution>
</institution-wrap>
Hefei, 230039 Anhui China</nlm:aff>
<wicri:noCountry code="subfield">230039 Anhui China</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Microbial and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Liu, Peipei" sort="Liu, Peipei" uniqKey="Liu P" first="Peipei" last="Liu">Peipei Liu</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff4">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.214572.7</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1936 8294</institution-id>
<institution>Departments of Microbiology and Pediatrics,</institution>
<institution>University of Iowa,</institution>
</institution-wrap>
Iowa City, 52242 IA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Iowa</region>
</placeName>
<wicri:regionArea>Iowa City</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff11">State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120 Guangdong China</nlm:aff>
<wicri:noCountry code="subfield">510120 Guangdong China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name>
<affiliation>
<nlm:aff id="Aff5">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041 Sichuan China</nlm:aff>
<wicri:noCountry code="subfield">610041 Sichuan China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wang, Qihui" sort="Wang, Qihui" uniqKey="Wang Q" first="Qihui" last="Wang">Qihui Wang</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Microbial and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lu, Xuancheng" sort="Lu, Xuancheng" uniqKey="Lu X" first="Xuancheng" last="Lu">Xuancheng Lu</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff6">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>Laboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC),</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wu, Ying" sort="Wu, Ying" uniqKey="Wu Y" first="Ying" last="Wu">Ying Wu</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Liu, Wenjun" sort="Liu, Wenjun" uniqKey="Liu W" first="Wenjun" last="Liu">Wenjun Liu</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Zhang, Buchang" sort="Zhang, Buchang" uniqKey="Zhang B" first="Buchang" last="Zhang">Buchang Zhang</name>
<affiliation>
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.252245.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0085 4987</institution-id>
<institution>School of Life Sciences, Anhui University,</institution>
</institution-wrap>
Hefei, 230039 Anhui China</nlm:aff>
<wicri:noCountry code="subfield">230039 Anhui China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation>
<nlm:aff id="Aff7">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong,</institution>
</institution-wrap>
Pokfulam, Hong Kong SAR China</nlm:aff>
<wicri:noCountry code="subfield">Hong Kong SAR China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff4">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.214572.7</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 1936 8294</institution-id>
<institution>Departments of Microbiology and Pediatrics,</institution>
<institution>University of Iowa,</institution>
</institution-wrap>
Iowa City, 52242 IA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Iowa</region>
</placeName>
<wicri:regionArea>Iowa City</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F" last="Gao">George F. Gao</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.252245.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0085 4987</institution-id>
<institution>School of Life Sciences, Anhui University,</institution>
</institution-wrap>
Hefei, 230039 Anhui China</nlm:aff>
<wicri:noCountry code="subfield">230039 Anhui China</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff8">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC),</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff9">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>China-Japan Joint Laboratory of Molecular Microbiology and Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff10">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.198530.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0000 8803 2373</institution-id>
<institution>Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC),</institution>
</institution-wrap>
Beijing, 102206 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.252245.6</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0085 4987</institution-id>
<institution>School of Life Sciences, Anhui University,</institution>
</institution-wrap>
Hefei, 230039 Anhui China</nlm:aff>
<wicri:noCountry code="subfield">230039 Anhui China</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.458488.d</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0627 1442</institution-id>
<institution>CAS Key Laboratory of Microbial and Metabolic engineering, Institute of Microbiology, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Cell Research</title>
<idno type="ISSN">1001-0602</idno>
<idno type="eISSN">1748-7838</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Animals</term>
<term>Antibodies, Monoclonal, Humanized (administration & dosage)</term>
<term>Antibodies, Monoclonal, Humanized (chemistry)</term>
<term>Antibodies, Monoclonal, Humanized (immunology)</term>
<term>Antibodies, Neutralizing (administration & dosage)</term>
<term>Antibodies, Neutralizing (chemistry)</term>
<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Viral (administration & dosage)</term>
<term>Antibodies, Viral (chemistry)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (therapeutic use)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux</term>
<term>Anticorps antiviraux ()</term>
<term>Anticorps antiviraux (administration et posologie)</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps monoclonaux humanisés ()</term>
<term>Anticorps monoclonaux humanisés (administration et posologie)</term>
<term>Anticorps monoclonaux humanisés (immunologie)</term>
<term>Anticorps neutralisants ()</term>
<term>Anticorps neutralisants (administration et posologie)</term>
<term>Anticorps neutralisants (immunologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Glycoprotéine de spicule des coronavirus (usage thérapeutique)</term>
<term>Infections à coronavirus (traitement médicamenteux)</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en">
<term>Antibodies, Monoclonal, Humanized</term>
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Antibodies, Monoclonal, Humanized</term>
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Antibodies, Monoclonal, Humanized</term>
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux humanisés</term>
<term>Anticorps neutralisants</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Coronavirus Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux humanisés</term>
<term>Anticorps neutralisants</term>
<term>Glycoprotéine de spicule des coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en">
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr">
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Glycoprotéine de spicule des coronavirus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux humanisés</term>
<term>Anticorps neutralisants</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="Par1">The newly-emerging Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans. Despite global efforts, the potential for an associated pandemic in the future cannot be excluded. The development of effective counter-measures is urgent. MERS-CoV-specific anti-viral drugs or vaccines are not yet available. Using the spike receptor-binding domain of MERS-CoV (MERS-RBD) to immunize mice, we identified two neutralizing monoclonal antibodies (mAbs) 4C2 and 2E6. Both mAbs potently bind to MERS-RBD and block virus entry
<italic>in vitro</italic>
with high efficacy. We further investigated their mechanisms of neutralization by crystallizing the complex between the Fab fragments and the RBD, and solved the structure of the 4C2 Fab/MERS-RBD complex. The structure showed that 4C2 recognizes an epitope that partially overlaps the receptor-binding footprint in MERS-RBD, thereby interfering with the virus/receptor interactions by both steric hindrance and interface-residue competition. 2E6 also blocks receptor binding, and competes with 4C2 for binding to MERS-RBD. Based on the structure, we further humanized 4C2 by preserving only the paratope residues and substituting the remaining amino acids with the counterparts from human immunoglobulins. The humanized 4C2 (4C2h) antibody sustained similar neutralizing activity and biochemical characteristics to the parental mouse antibody. Finally, we showed that 4C2h can significantly abate the virus titers in lungs of Ad5-hCD26-transduced mice infected with MERS-CoV, therefore representing a promising agent for prophylaxis and therapy in clinical settings.</p>
</div>
</front>
<back>
<div1 type="bibliography">
<listBibl>
<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="Chan, Jf" uniqKey="Chan J">JF Chan</name>
</author>
<author>
<name sortKey="Li, Ks" uniqKey="Li K">KS Li</name>
</author>
<author>
<name sortKey="To, Kk" uniqKey="To K">KK To</name>
</author>
<author>
<name sortKey="Cheng, Vc" uniqKey="Cheng V">VC Cheng</name>
</author>
<author>
<name sortKey="Chen, H" uniqKey="Chen H">H Chen</name>
</author>
<author>
<name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Zhong, Ns" uniqKey="Zhong N">NS Zhong</name>
</author>
<author>
<name sortKey="Zheng, Bj" uniqKey="Zheng B">BJ Zheng</name>
</author>
<author>
<name sortKey="Li, Ym" uniqKey="Li Y">YM Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Breban, R" uniqKey="Breban R">R Breban</name>
</author>
<author>
<name sortKey="Riou, J" uniqKey="Riou J">J Riou</name>
</author>
<author>
<name sortKey="Fontanet, A" uniqKey="Fontanet A">A Fontanet</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Su, S" uniqKey="Su S">S Su</name>
</author>
<author>
<name sortKey="Wong, G" uniqKey="Wong G">G Wong</name>
</author>
<author>
<name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name>
</author>
<author>
<name sortKey="Gao, Gf" uniqKey="Gao G">GF Gao</name>
</author>
<author>
<name sortKey="Li, S" uniqKey="Li S">S Li</name>
</author>
<author>
<name sortKey="Bi, Y" uniqKey="Bi Y">Y Bi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lu, G" uniqKey="Lu G">G Lu</name>
</author>
<author>
<name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name>
</author>
<author>
<name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name>
</author>
</analytic>
</biblStruct>
<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="Du, L" uniqKey="Du L">L Du</name>
</author>
<author>
<name sortKey="He, Y" uniqKey="He Y">Y He</name>
</author>
<author>
<name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name>
</author>
<author>
<name sortKey="Liu, S" uniqKey="Liu S">S Liu</name>
</author>
<author>
<name sortKey="Zheng, Bj" uniqKey="Zheng B">BJ Zheng</name>
</author>
<author>
<name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</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="Raj, Vs" uniqKey="Raj V">VS Raj</name>
</author>
<author>
<name sortKey="Mou, Hh" uniqKey="Mou H">HH Mou</name>
</author>
<author>
<name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</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="Lu, G" uniqKey="Lu G">G Lu</name>
</author>
<author>
<name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name>
</author>
<author>
<name sortKey="Gao, Gf" uniqKey="Gao G">GF Gao</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Wang, N" uniqKey="Wang N">N Wang</name>
</author>
<author>
<name sortKey="Shi, X" uniqKey="Shi X">X Shi</name>
</author>
<author>
<name sortKey="Jiang, L" uniqKey="Jiang L">L Jiang</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Gao, J" uniqKey="Gao J">J Gao</name>
</author>
<author>
<name sortKey="Lu, G" uniqKey="Lu G">G Lu</name>
</author>
<author>
<name sortKey="Qi, J" uniqKey="Qi J">J Qi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lu, L" uniqKey="Lu L">L Lu</name>
</author>
<author>
<name sortKey="Liu, Q" uniqKey="Liu Q">Q Liu</name>
</author>
<author>
<name sortKey="Zhu, Y" uniqKey="Zhu Y">Y Zhu</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Du, L" uniqKey="Du L">L Du</name>
</author>
<author>
<name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name>
</author>
<author>
<name sortKey="Kou, Z" uniqKey="Kou Z">Z Kou</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Du, L" uniqKey="Du L">L Du</name>
</author>
<author>
<name sortKey="Kou, Z" uniqKey="Kou Z">Z Kou</name>
</author>
<author>
<name sortKey="Ma, C" uniqKey="Ma C">C Ma</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Song, F" uniqKey="Song F">F Song</name>
</author>
<author>
<name sortKey="Fux, R" uniqKey="Fux R">R Fux</name>
</author>
<author>
<name sortKey="Provacia, Lb" uniqKey="Provacia L">LB Provacia</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Tang, Xc" uniqKey="Tang X">XC Tang</name>
</author>
<author>
<name sortKey="Agnihothram, Ss" uniqKey="Agnihothram S">SS Agnihothram</name>
</author>
<author>
<name sortKey="Jiao, Y" uniqKey="Jiao Y">Y Jiao</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Jiang, L" uniqKey="Jiang L">L Jiang</name>
</author>
<author>
<name sortKey="Wang, N" uniqKey="Wang N">N Wang</name>
</author>
<author>
<name sortKey="Zuo, T" uniqKey="Zuo T">T Zuo</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Pascal, Ke" uniqKey="Pascal K">KE Pascal</name>
</author>
<author>
<name sortKey="Coleman, Cm" uniqKey="Coleman C">CM Coleman</name>
</author>
<author>
<name sortKey="Mujica, Ao" uniqKey="Mujica A">AO Mujica</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name>
</author>
<author>
<name sortKey="Li, K" uniqKey="Li K">K Li</name>
</author>
<author>
<name sortKey="Wohlford Lenane, C" uniqKey="Wohlford Lenane C">C Wohlford-Lenane</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name>
</author>
<author>
<name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name>
</author>
<author>
<name sortKey="Rasmussen, Al" uniqKey="Rasmussen A">AL Rasmussen</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Omrani, As" uniqKey="Omrani A">AS Omrani</name>
</author>
<author>
<name sortKey="Saad, Mm" uniqKey="Saad M">MM Saad</name>
</author>
<author>
<name sortKey="Baig, K" uniqKey="Baig K">K Baig</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="D Souza, P" uniqKey="D Souza P">P D'Souza</name>
</author>
<author>
<name sortKey="Walker, G" uniqKey="Walker G">G Walker</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Murray, J" uniqKey="Murray J">J Murray</name>
</author>
<author>
<name sortKey="Saxena, S" uniqKey="Saxena S">S Saxena</name>
</author>
<author>
<name sortKey="Sharland, M" uniqKey="Sharland M">M Sharland</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Jacob, J" uniqKey="Jacob J">J Jacob</name>
</author>
<author>
<name sortKey="Kirova, Ym" uniqKey="Kirova Y">YM Kirova</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Qiu, X" uniqKey="Qiu X">X Qiu</name>
</author>
<author>
<name sortKey="Wong, G" uniqKey="Wong G">G Wong</name>
</author>
<author>
<name sortKey="Audet, J" uniqKey="Audet J">J Audet</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bermingham, A" uniqKey="Bermingham A">A Bermingham</name>
</author>
<author>
<name sortKey="Chand, Ma" uniqKey="Chand M">MA Chand</name>
</author>
<author>
<name sortKey="Brown, Cs" uniqKey="Brown C">CS Brown</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Liu, J" uniqKey="Liu J">J Liu</name>
</author>
<author>
<name sortKey="Lester, P" uniqKey="Lester P">P Lester</name>
</author>
<author>
<name sortKey="Builder, S" uniqKey="Builder S">S Builder</name>
</author>
<author>
<name sortKey="Shire, Sj" uniqKey="Shire S">SJ Shire</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Muller, Ya" uniqKey="Muller Y">YA Muller</name>
</author>
<author>
<name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name>
</author>
<author>
<name sortKey="Christinger, Hw" uniqKey="Christinger H">HW Christinger</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Faelber, K" uniqKey="Faelber K">K Faelber</name>
</author>
<author>
<name sortKey="Kirchhofer, D" uniqKey="Kirchhofer D">D Kirchhofer</name>
</author>
<author>
<name sortKey="Presta, L" uniqKey="Presta L">L Presta</name>
</author>
<author>
<name sortKey="Kelley, Rf" uniqKey="Kelley R">RF Kelley</name>
</author>
<author>
<name sortKey="Muller, Ya" uniqKey="Muller Y">YA Muller</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Karpusas, M" uniqKey="Karpusas M">M Karpusas</name>
</author>
<author>
<name sortKey="Lucci, J" uniqKey="Lucci J">J Lucci</name>
</author>
<author>
<name sortKey="Ferrant, J" uniqKey="Ferrant J">J Ferrant</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ying, T" uniqKey="Ying T">T Ying</name>
</author>
<author>
<name sortKey="Du, L" uniqKey="Du L">L Du</name>
</author>
<author>
<name sortKey="Ju, Tw" uniqKey="Ju T">TW Ju</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Huang, W" uniqKey="Huang W">W Huang</name>
</author>
<author>
<name sortKey="Samanta, M" uniqKey="Samanta M">M Samanta</name>
</author>
<author>
<name sortKey="Crawford, Se" uniqKey="Crawford S">SE Crawford</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Houimel, M" uniqKey="Houimel M">M Houimel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Avnir, Y" uniqKey="Avnir Y">Y Avnir</name>
</author>
<author>
<name sortKey="Tallarico, As" uniqKey="Tallarico A">AS Tallarico</name>
</author>
<author>
<name sortKey="Zhu, Q" uniqKey="Zhu Q">Q Zhu</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Li, M" uniqKey="Li M">M Li</name>
</author>
<author>
<name sortKey="Gao, F" uniqKey="Gao F">F Gao</name>
</author>
<author>
<name sortKey="Mascola, Jr" uniqKey="Mascola J">JR Mascola</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Chan, Kh" uniqKey="Chan K">KH Chan</name>
</author>
<author>
<name sortKey="Chan, Jf" uniqKey="Chan J">JF Chan</name>
</author>
<author>
<name sortKey="Tse, H" uniqKey="Tse H">H Tse</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Zheng, Bj" uniqKey="Zheng B">BJ Zheng</name>
</author>
<author>
<name sortKey="Chan, Kw" uniqKey="Chan K">KW Chan</name>
</author>
<author>
<name sortKey="Lin, Yp" uniqKey="Lin Y">YP Lin</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region>
<li>Iowa</li>
</region>
</list>
<tree>
<noCountry>
<name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Zhang, Buchang" sort="Zhang, Buchang" uniqKey="Zhang B" first="Buchang" last="Zhang">Buchang Zhang</name>
</noCountry>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name>
</noRegion>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F" last="Gao">George F. Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F" last="Gao">George F. Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F" last="Gao">George F. Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F" last="Gao">George F. Gao</name>
<name sortKey="Liu, Peipei" sort="Liu, Peipei" uniqKey="Liu P" first="Peipei" last="Liu">Peipei Liu</name>
<name sortKey="Liu, Wenjun" sort="Liu, Wenjun" uniqKey="Liu W" first="Wenjun" last="Liu">Wenjun Liu</name>
<name sortKey="Lu, Xuancheng" sort="Lu, Xuancheng" uniqKey="Lu X" first="Xuancheng" last="Lu">Xuancheng Lu</name>
<name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<name sortKey="Wan, Yuhua" sort="Wan, Yuhua" uniqKey="Wan Y" first="Yuhua" last="Wan">Yuhua Wan</name>
<name sortKey="Wan, Yuhua" sort="Wan, Yuhua" uniqKey="Wan Y" first="Yuhua" last="Wan">Yuhua Wan</name>
<name sortKey="Wang, Qihui" sort="Wang, Qihui" uniqKey="Wang Q" first="Qihui" last="Wang">Qihui Wang</name>
<name sortKey="Wu, Ying" sort="Wu, Ying" uniqKey="Wu Y" first="Ying" last="Wu">Ying Wu</name>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name>
</country>
<country name="États-Unis">
<region name="Iowa">
<name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name>
</region>
<name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
</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 001921 | SxmlIndent | more

Ou

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001921 | 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:4650419
   |texte=   A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:26391698" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a MersV1 

Wicri

This area was generated with Dilib version V0.6.33.
Data generation: Mon Apr 20 23:26:43 2020. Site generation: Sat Mar 27 09:06:09 2021