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Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV.

Identifieur interne : 000483 ( PubMed/Curation ); précédent : 000482; suivant : 000484

Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV.

Auteurs : Xiuyuan Ou [République populaire de Chine] ; Yan Liu [République populaire de Chine] ; Xiaobo Lei [République populaire de Chine] ; Pei Li [République populaire de Chine] ; Dan Mi [République populaire de Chine] ; Lili Ren [République populaire de Chine] ; Li Guo [République populaire de Chine] ; Ruixuan Guo [République populaire de Chine] ; Ting Chen [République populaire de Chine] ; Jiaxin Hu [République populaire de Chine] ; Zichun Xiang [République populaire de Chine] ; Zhixia Mu [République populaire de Chine] ; Xing Chen [République populaire de Chine] ; Jieyong Chen [République populaire de Chine] ; Keping Hu [République populaire de Chine] ; Qi Jin [République populaire de Chine] ; Jianwei Wang [République populaire de Chine] ; Zhaohui Qian [République populaire de Chine]

Source :

RBID : pubmed:32221306

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English descriptors

Abstract

Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.

DOI: 10.1038/s41467-020-15562-9
PubMed: 32221306

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pubmed:32221306

Le document en format XML

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<name sortKey="Liu, Yan" sort="Liu, Yan" uniqKey="Liu Y" first="Yan" last="Liu">Yan Liu</name>
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<name sortKey="Lei, Xiaobo" sort="Lei, Xiaobo" uniqKey="Lei X" first="Xiaobo" last="Lei">Xiaobo Lei</name>
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<name sortKey="Li, Pei" sort="Li, Pei" uniqKey="Li P" first="Pei" last="Li">Pei Li</name>
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<name sortKey="Mi, Dan" sort="Mi, Dan" uniqKey="Mi D" first="Dan" last="Mi">Dan Mi</name>
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<name sortKey="Ren, Lili" sort="Ren, Lili" uniqKey="Ren L" first="Lili" last="Ren">Lili Ren</name>
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<name sortKey="Guo, Li" sort="Guo, Li" uniqKey="Guo L" first="Li" last="Guo">Li Guo</name>
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<name sortKey="Mu, Zhixia" sort="Mu, Zhixia" uniqKey="Mu Z" first="Zhixia" last="Mu">Zhixia Mu</name>
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<name sortKey="Chen, Xing" sort="Chen, Xing" uniqKey="Chen X" first="Xing" last="Chen">Xing Chen</name>
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<name sortKey="Chen, Jieyong" sort="Chen, Jieyong" uniqKey="Chen J" first="Jieyong" last="Chen">Jieyong Chen</name>
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<name sortKey="Hu, Keping" sort="Hu, Keping" uniqKey="Hu K" first="Keping" last="Hu">Keping Hu</name>
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<nlm:affiliation>Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC), 151 Malianwa Road North, Haidian District, 100193, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC), 151 Malianwa Road North, Haidian District, 100193, Beijing</wicri:regionArea>
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<name sortKey="Jin, Qi" sort="Jin, Qi" uniqKey="Jin Q" first="Qi" last="Jin">Qi Jin</name>
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<nlm:affiliation>NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing, China. jinqi@ipbcams.ac.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing</wicri:regionArea>
</affiliation>
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<name sortKey="Wang, Jianwei" sort="Wang, Jianwei" uniqKey="Wang J" first="Jianwei" last="Wang">Jianwei Wang</name>
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<nlm:affiliation>NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing, China. wangjw28@163.com.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing</wicri:regionArea>
</affiliation>
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<name sortKey="Qian, Zhaohui" sort="Qian, Zhaohui" uniqKey="Qian Z" first="Zhaohui" last="Qian">Zhaohui Qian</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<series>
<title level="j">Nature communications</title>
<idno type="eISSN">2041-1723</idno>
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<date when="2020" type="published">2020</date>
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<term>Antibodies, Viral (immunology)</term>
<term>Betacoronavirus (chemistry)</term>
<term>Betacoronavirus (immunology)</term>
<term>Betacoronavirus (physiology)</term>
<term>Broadly Neutralizing Antibodies (immunology)</term>
<term>Calcium Channels (metabolism)</term>
<term>Cathepsin L (metabolism)</term>
<term>Cathepsins (antagonists & inhibitors)</term>
<term>Cathepsins (metabolism)</term>
<term>Cell Fusion</term>
<term>Coronavirus Infections (immunology)</term>
<term>Cross Reactions</term>
<term>Endocytosis</term>
<term>Giant Cells (physiology)</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Neutralization Tests</term>
<term>Pandemics</term>
<term>Peptidyl-Dipeptidase A (metabolism)</term>
<term>Phosphatidylinositol 3-Kinases (metabolism)</term>
<term>Pneumonia, Viral (immunology)</term>
<term>Protein Domains</term>
<term>Protein Multimerization</term>
<term>Receptors, Virus (metabolism)</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (chemistry)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (metabolism)</term>
<term>Trypsin (metabolism)</term>
<term>Virus Internalization</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Anticorps antiviraux (immunologie)</term>
<term>Canaux calciques (métabolisme)</term>
<term>Cathepsine L (métabolisme)</term>
<term>Cathepsines (antagonistes et inhibiteurs)</term>
<term>Cathepsines (métabolisme)</term>
<term>Cellules HEK293</term>
<term>Cellules géantes (physiologie)</term>
<term>Domaines protéiques</term>
<term>Endocytose</term>
<term>Fusion cellulaire</term>
<term>Glycoprotéine de spicule des coronavirus ()</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Humains</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Multimérisation de protéines</term>
<term>Pandémies</term>
<term>Peptidyl-Dipeptidase A (métabolisme)</term>
<term>Phosphatidylinositol 3-kinases (métabolisme)</term>
<term>Pneumopathie virale (immunologie)</term>
<term>Pénétration virale</term>
<term>Réactions croisées</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Tests de neutralisation</term>
<term>Trypsine (métabolisme)</term>
<term>Virus du SRAS (immunologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en">
<term>Cathepsins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Antibodies, Viral</term>
<term>Broadly Neutralizing Antibodies</term>
<term>Spike Glycoprotein, Coronavirus</term>
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<term>Cathepsines</term>
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<keywords scheme="MESH" qualifier="chemistry" xml:lang="en">
<term>Betacoronavirus</term>
</keywords>
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<term>Anticorps antiviraux</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
</keywords>
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<term>Betacoronavirus</term>
<term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
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<term>Calcium Channels</term>
<term>Cathepsin L</term>
<term>Cathepsins</term>
<term>Peptidyl-Dipeptidase A</term>
<term>Phosphatidylinositol 3-Kinases</term>
<term>Receptors, Virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Trypsin</term>
</keywords>
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<term>Canaux calciques</term>
<term>Cathepsine L</term>
<term>Cathepsines</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Peptidyl-Dipeptidase A</term>
<term>Phosphatidylinositol 3-kinases</term>
<term>Récepteurs viraux</term>
<term>Trypsine</term>
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<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Cellules géantes</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en">
<term>Betacoronavirus</term>
<term>Giant Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Cell Fusion</term>
<term>Cross Reactions</term>
<term>Endocytosis</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Neutralization Tests</term>
<term>Pandemics</term>
<term>Protein Domains</term>
<term>Protein Multimerization</term>
<term>Virus Internalization</term>
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<term>Cellules HEK293</term>
<term>Domaines protéiques</term>
<term>Endocytose</term>
<term>Fusion cellulaire</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Multimérisation de protéines</term>
<term>Pandémies</term>
<term>Pénétration virale</term>
<term>Réactions croisées</term>
<term>Tests de neutralisation</term>
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<front>
<div type="abstract" xml:lang="en">Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.</div>
</front>
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<PMID Version="1">32221306</PMID>
<DateCompleted>
<Year>2020</Year>
<Month>04</Month>
<Day>02</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>04</Month>
<Day>15</Day>
</DateRevised>
<Article PubModel="Electronic">
<Journal>
<ISSN IssnType="Electronic">2041-1723</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>11</Volume>
<Issue>1</Issue>
<PubDate>
<Year>2020</Year>
<Month>03</Month>
<Day>27</Day>
</PubDate>
</JournalIssue>
<Title>Nature communications</Title>
<ISOAbbreviation>Nat Commun</ISOAbbreviation>
</Journal>
<ArticleTitle>Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV.</ArticleTitle>
<Pagination>
<MedlinePgn>1620</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/s41467-020-15562-9</ELocationID>
<Abstract>
<AbstractText>Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.</AbstractText>
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<LastName>Ou</LastName>
<ForeName>Xiuyuan</ForeName>
<Initials>X</Initials>
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</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Liu</LastName>
<ForeName>Yan</ForeName>
<Initials>Y</Initials>
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</AffiliationInfo>
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<LastName>Lei</LastName>
<ForeName>Xiaobo</ForeName>
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<ForeName>Pei</ForeName>
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<ForeName>Dan</ForeName>
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<Affiliation>NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing, China. zqian2013@sina.com.</Affiliation>
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<GrantList CompleteYN="Y">
<Grant>
<GrantID>31970171</GrantID>
<Agency>National Natural Science Foundation of China (National Science Foundation of China)</Agency>
<Country>International</Country>
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<Grant>
<GrantID>31670164</GrantID>
<Agency>National Natural Science Foundation of China (National Science Foundation of China)</Agency>
<Country>International</Country>
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<MeshHeading>
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<MeshHeading>
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<PubMedPubDate PubStatus="received">
<Year>2020</Year>
<Month>02</Month>
<Day>13</Day>
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<PubMedPubDate PubStatus="accepted">
<Year>2020</Year>
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