Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein
Identifieur interne : 000369 ( Main/Exploration ); précédent : 000368; suivant : 000370Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein
Auteurs : Haixia Zhou [République populaire de Chine] ; Yingzhu Chen [République populaire de Chine] ; Shuyuan Zhang [République populaire de Chine] ; Peihua Niu [République populaire de Chine] ; Kun Qin [République populaire de Chine] ; Wenxu Jia [République populaire de Chine] ; Baoying Huang [République populaire de Chine] ; Senyan Zhang [République populaire de Chine] ; Jun Lan [République populaire de Chine] ; Linqi Zhang [République populaire de Chine] ; Wenjie Tan [République populaire de Chine] ; Xinquan Wang [République populaire de Chine]Source :
- Nature Communications [ 2041-1723 ] ; 2019.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps antiviraux (métabolisme), Anticorps antiviraux (sang), Anticorps antiviraux (ultrastructure), Anticorps neutralisants (immunologie), Anticorps neutralisants (métabolisme), Anticorps neutralisants (sang), Anticorps neutralisants (ultrastructure), Cartographie épitopique, Cellules HEK293, Cellules Vero, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme), Cristallographie aux rayons X, Dipeptidyl peptidase 4 (métabolisme), Domaines protéiques (immunologie), Femelle, Glycoprotéine de spicule des coronavirus (immunologie), Glycoprotéine de spicule des coronavirus (isolement et purification), Glycoprotéine de spicule des coronavirus (métabolisme), Glycoprotéine de spicule des coronavirus (ultrastructure), Humains, Infections à coronavirus (immunologie), Infections à coronavirus (sang), Infections à coronavirus (virologie), Liaison aux protéines (immunologie), Lignée cellulaire tumorale, Modèles animaux de maladie humaine, Protéines recombinantes (immunologie), Protéines recombinantes (isolement et purification), Protéines recombinantes (métabolisme), Protéines recombinantes (ultrastructure), Pénétration virale, Souris, Tests de neutralisation, Épitopes (immunologie).
- MESH :
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Domaines protéiques, Glycoprotéine de spicule des coronavirus, Infections à coronavirus, Liaison aux protéines, Protéines recombinantes, Épitopes.
- isolement et purification : Glycoprotéine de spicule des coronavirus, Protéines recombinantes.
- métabolisme : Anticorps antiviraux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Dipeptidyl peptidase 4, Glycoprotéine de spicule des coronavirus, Protéines recombinantes.
- sang : Anticorps antiviraux, Anticorps neutralisants, Infections à coronavirus.
- ultrastructure : Anticorps antiviraux, Anticorps neutralisants, Glycoprotéine de spicule des coronavirus, Protéines recombinantes.
- virologie : Infections à coronavirus.
- Animaux, Cartographie épitopique, Cellules HEK293, Cellules Vero, Cristallographie aux rayons X, Femelle, Humains, Lignée cellulaire tumorale, Modèles animaux de maladie humaine, Pénétration virale, Souris, Tests de neutralisation.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (blood), Antibodies, Neutralizing (immunology), Antibodies, Neutralizing (metabolism), Antibodies, Neutralizing (ultrastructure), Antibodies, Viral (blood), Antibodies, Viral (immunology), Antibodies, Viral (metabolism), Antibodies, Viral (ultrastructure), Cell Line, Tumor, Chlorocebus aethiops, Coronavirus Infections (blood), Coronavirus Infections (immunology), Coronavirus Infections (virology), Crystallography, X-Ray, Dipeptidyl Peptidase 4 (metabolism), Disease Models, Animal, Epitope Mapping, Epitopes (immunology), Female, HEK293 Cells, Humans, Mice, Middle East Respiratory Syndrome Coronavirus (immunology), Middle East Respiratory Syndrome Coronavirus (metabolism), Neutralization Tests, Protein Binding (immunology), Protein Domains (immunology), Recombinant Proteins (immunology), Recombinant Proteins (isolation & purification), Recombinant Proteins (metabolism), Recombinant Proteins (ultrastructure), Spike Glycoprotein, Coronavirus (immunology), Spike Glycoprotein, Coronavirus (isolation & purification), Spike Glycoprotein, Coronavirus (metabolism), Spike Glycoprotein, Coronavirus (ultrastructure), Vero Cells, Virus Internalization.
- MESH :
- chemical , blood : Antibodies, Neutralizing, Antibodies, Viral.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Epitopes, Recombinant Proteins, Spike Glycoprotein, Coronavirus.
- chemical , isolation & purification : Recombinant Proteins, Spike Glycoprotein, Coronavirus.
- chemical , metabolism : Antibodies, Neutralizing, Antibodies, Viral, Dipeptidyl Peptidase 4, Recombinant Proteins, Spike Glycoprotein, Coronavirus.
- chemical , ultrastructure : Antibodies, Neutralizing, Antibodies, Viral, Recombinant Proteins, Spike Glycoprotein, Coronavirus.
- blood : Coronavirus Infections.
- immunology : Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus, Protein Binding, Protein Domains.
- metabolism : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections.
- Animals, Cell Line, Tumor, Chlorocebus aethiops, Crystallography, X-Ray, Disease Models, Animal, Epitope Mapping, Female, HEK293 Cells, Humans, Mice, Neutralization Tests, Vero Cells, Virus Internalization.
Abstract
Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.
Url:
DOI: 10.1038/s41467-019-10897-4
PubMed: 31296843
PubMed Central: 6624210
Affiliations:
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Le document en format XML
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institution-id-type="GRID">grid.12527.33</institution-id><institution>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences,</institution><institution>Tsinghua University,</institution></institution-wrap>100084 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100084 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yingzhu" sort="Chen, Yingzhu" uniqKey="Chen Y" first="Yingzhu" last="Chen">Yingzhu Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0027 0586</institution-id><institution-id institution-id-type="GRID">grid.412474.0</institution-id><institution>Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory,</institution><institution>Peking University Cancer Hospital & Institute,</institution></institution-wrap>100142 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100142 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Shuyuan" sort="Zhang, Shuyuan" uniqKey="Zhang S" first="Shuyuan" last="Zhang">Shuyuan Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences,</institution><institution>Tsinghua University,</institution></institution-wrap>100084 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100084 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Niu, Peihua" sort="Niu, Peihua" uniqKey="Niu P" first="Peihua" last="Niu">Peihua Niu</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Qin, Kun" sort="Qin, Kun" uniqKey="Qin K" first="Kun" last="Qin">Kun Qin</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Jia, Wenxu" sort="Jia, Wenxu" uniqKey="Jia W" first="Wenxu" last="Jia">Wenxu Jia</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine,</institution><institution> Tsinghua University,</institution></institution-wrap>100084 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100084 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Huang, Baoying" sort="Huang, Baoying" uniqKey="Huang B" first="Baoying" last="Huang">Baoying Huang</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Senyan" sort="Zhang, Senyan" uniqKey="Zhang S" first="Senyan" last="Zhang">Senyan Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences,</institution><institution>Tsinghua University,</institution></institution-wrap>100084 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100084 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Lan, Jun" sort="Lan, Jun" uniqKey="Lan J" first="Jun" last="Lan">Jun Lan</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences,</institution><institution>Tsinghua University,</institution></institution-wrap>100084 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100084 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine,</institution><institution> Tsinghua University,</institution></institution-wrap>100084 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100084 Beijing</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="1"><nlm:aff id="Aff2">Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences,</institution><institution>Tsinghua University,</institution></institution-wrap>100084 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100084 Beijing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School,</institution><institution>Sichuan University,</institution></institution-wrap>610065 Chengdu, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>610065 Chengdu</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Neutralizing (blood)</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Neutralizing (metabolism)</term><term>Antibodies, Neutralizing (ultrastructure)</term><term>Antibodies, Viral (blood)</term><term>Antibodies, Viral (immunology)</term><term>Antibodies, Viral (metabolism)</term><term>Antibodies, Viral (ultrastructure)</term><term>Cell Line, Tumor</term><term>Chlorocebus aethiops</term><term>Coronavirus Infections (blood)</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (virology)</term><term>Crystallography, X-Ray</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Disease Models, Animal</term><term>Epitope Mapping</term><term>Epitopes (immunology)</term><term>Female</term><term>HEK293 Cells</term><term>Humans</term><term>Mice</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term><term>Neutralization Tests</term><term>Protein Binding (immunology)</term><term>Protein Domains (immunology)</term><term>Recombinant Proteins (immunology)</term><term>Recombinant Proteins (isolation & purification)</term><term>Recombinant Proteins (metabolism)</term><term>Recombinant Proteins (ultrastructure)</term><term>Spike Glycoprotein, Coronavirus (immunology)</term><term>Spike Glycoprotein, Coronavirus (isolation & purification)</term><term>Spike Glycoprotein, Coronavirus (metabolism)</term><term>Spike Glycoprotein, Coronavirus (ultrastructure)</term><term>Vero Cells</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps antiviraux (métabolisme)</term><term>Anticorps antiviraux (sang)</term><term>Anticorps antiviraux (ultrastructure)</term><term>Anticorps neutralisants (immunologie)</term><term>Anticorps neutralisants (métabolisme)</term><term>Anticorps neutralisants (sang)</term><term>Anticorps neutralisants (ultrastructure)</term><term>Cartographie épitopique</term><term>Cellules HEK293</term><term>Cellules Vero</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme)</term><term>Cristallographie aux rayons X</term><term>Dipeptidyl peptidase 4 (métabolisme)</term><term>Domaines protéiques (immunologie)</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus (immunologie)</term><term>Glycoprotéine de spicule des coronavirus (isolement et purification)</term><term>Glycoprotéine de spicule des coronavirus (métabolisme)</term><term>Glycoprotéine de spicule des coronavirus (ultrastructure)</term><term>Humains</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (sang)</term><term>Infections à coronavirus (virologie)</term><term>Liaison aux protéines (immunologie)</term><term>Lignée cellulaire tumorale</term><term>Modèles animaux de maladie humaine</term><term>Protéines recombinantes (immunologie)</term><term>Protéines recombinantes (isolement et purification)</term><term>Protéines recombinantes (métabolisme)</term><term>Protéines recombinantes (ultrastructure)</term><term>Pénétration virale</term><term>Souris</term><term>Tests de neutralisation</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Epitopes</term><term>Recombinant Proteins</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Recombinant Proteins</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Dipeptidyl Peptidase 4</term><term>Recombinant Proteins</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="ultrastructure" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Recombinant Proteins</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Domaines protéiques</term><term>Glycoprotéine de spicule des coronavirus</term><term>Infections à coronavirus</term><term>Liaison aux protéines</term><term>Protéines recombinantes</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>Protein Binding</term><term>Protein Domains</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term><term>Protéines recombinantes</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Dipeptidyl peptidase 4</term><term>Glycoprotéine de spicule des coronavirus</term><term>Protéines recombinantes</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Glycoprotéine de spicule des coronavirus</term><term>Protéines recombinantes</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Chlorocebus aethiops</term><term>Crystallography, X-Ray</term><term>Disease Models, Animal</term><term>Epitope Mapping</term><term>Female</term><term>HEK293 Cells</term><term>Humans</term><term>Mice</term><term>Neutralization Tests</term><term>Vero Cells</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cartographie épitopique</term><term>Cellules HEK293</term><term>Cellules Vero</term><term>Cristallographie aux rayons X</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Modèles animaux de maladie humaine</term><term>Pénétration virale</term><term>Souris</term><term>Tests de neutralisation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.</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="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haagmans, Bl" 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Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Zhou, Haixia" sort="Zhou, Haixia" uniqKey="Zhou H" first="Haixia" last="Zhou">Haixia Zhou</name></noRegion><name sortKey="Chen, Yingzhu" sort="Chen, Yingzhu" uniqKey="Chen Y" first="Yingzhu" last="Chen">Yingzhu Chen</name><name sortKey="Chen, Yingzhu" sort="Chen, Yingzhu" uniqKey="Chen Y" first="Yingzhu" last="Chen">Yingzhu Chen</name><name sortKey="Huang, Baoying" sort="Huang, Baoying" uniqKey="Huang B" first="Baoying" last="Huang">Baoying Huang</name><name sortKey="Jia, Wenxu" sort="Jia, Wenxu" uniqKey="Jia W" first="Wenxu" last="Jia">Wenxu Jia</name><name sortKey="Lan, Jun" sort="Lan, Jun" uniqKey="Lan J" first="Jun" last="Lan">Jun Lan</name><name sortKey="Niu, Peihua" sort="Niu, Peihua" uniqKey="Niu P" first="Peihua" last="Niu">Peihua Niu</name><name sortKey="Qin, Kun" sort="Qin, Kun" uniqKey="Qin K" first="Kun" last="Qin">Kun Qin</name><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name><name sortKey="Wang, Xinquan" sort="Wang, Xinquan" uniqKey="Wang X" first="Xinquan" last="Wang">Xinquan Wang</name><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><name sortKey="Zhang, Senyan" sort="Zhang, Senyan" uniqKey="Zhang S" first="Senyan" last="Zhang">Senyan Zhang</name><name sortKey="Zhang, Shuyuan" sort="Zhang, Shuyuan" uniqKey="Zhang S" first="Shuyuan" last="Zhang">Shuyuan Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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