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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 : 000853 ( Main/Exploration ); précédent : 000852; suivant : 000854

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 : PMC:7100515

Descripteurs français

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.


Url:
DOI: 10.1038/s41467-020-15562-9
PubMed: 32221306
PubMed Central: 7100515


Affiliations:


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


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<wicri:regionArea>100176 Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Guo, Ruixuan" sort="Guo, Ruixuan" uniqKey="Guo R" first="Ruixuan" last="Guo">Ruixuan Guo</name>
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<institution>NHC Key laboratory of Systems Biology of Pathogens,</institution>
<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution>
</institution-wrap>
100176 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>100176 Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Chen, Ting" sort="Chen, Ting" uniqKey="Chen T" first="Ting" last="Chen">Ting Chen</name>
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<nlm:aff id="Aff1">
<institution-wrap>
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<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution>
</institution-wrap>
100176 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>100176 Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hu, Jiaxin" sort="Hu, Jiaxin" uniqKey="Hu J" first="Jiaxin" last="Hu">Jiaxin Hu</name>
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<nlm:aff id="Aff1">
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<institution>NHC Key laboratory of Systems Biology of Pathogens,</institution>
<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution>
</institution-wrap>
100176 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>100176 Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Xiang, Zichun" sort="Xiang, Zichun" uniqKey="Xiang Z" first="Zichun" last="Xiang">Zichun Xiang</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff1">
<institution-wrap>
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<institution-id institution-id-type="GRID">grid.12527.33</institution-id>
<institution>NHC Key laboratory of Systems Biology of Pathogens,</institution>
<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution>
</institution-wrap>
100176 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>100176 Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mu, Zhixia" sort="Mu, Zhixia" uniqKey="Mu Z" first="Zhixia" last="Mu">Zhixia Mu</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>NHC Key laboratory of Systems Biology of Pathogens,</institution>
<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution>
</institution-wrap>
100176 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>100176 Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Chen, Xing" sort="Chen, Xing" uniqKey="Chen X" first="Xing" last="Chen">Xing Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff2">
<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>Institute of Medicinal Plant Development (IMPLAD),</institution>
<institution>Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC),</institution>
</institution-wrap>
151 Malianwa Road North, Haidian District, 100193 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>151 Malianwa Road North, Haidian District, 100193 Beijing</wicri:regionArea>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Chen, Jieyong" sort="Chen, Jieyong" uniqKey="Chen J" first="Jieyong" last="Chen">Jieyong Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff3">Hengshui Third People’s Hospital, Heibei, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Hengshui Third People’s Hospital, Heibei</wicri:regionArea>
<wicri:noRegion>Heibei</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hu, Keping" sort="Hu, Keping" uniqKey="Hu K" first="Keping" last="Hu">Keping Hu</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff2">
<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>Institute of Medicinal Plant Development (IMPLAD),</institution>
<institution>Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC),</institution>
</institution-wrap>
151 Malianwa Road North, Haidian District, 100193 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>151 Malianwa Road North, Haidian District, 100193 Beijing</wicri:regionArea>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jin, Qi" sort="Jin, Qi" uniqKey="Jin Q" first="Qi" last="Jin">Qi Jin</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>NHC Key laboratory of Systems Biology of Pathogens,</institution>
<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution>
</institution-wrap>
100176 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>100176 Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wang, Jianwei" sort="Wang, Jianwei" uniqKey="Wang J" first="Jianwei" last="Wang">Jianwei 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>NHC Key laboratory of Systems Biology of Pathogens,</institution>
<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution>
</institution-wrap>
100176 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>100176 Beijing</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Qian, Zhaohui" sort="Qian, Zhaohui" uniqKey="Qian Z" first="Zhaohui" last="Qian">Zhaohui Qian</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>NHC Key laboratory of Systems Biology of Pathogens,</institution>
<institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution>
</institution-wrap>
100176 Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>100176 Beijing</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint>
<date when="2020">2020</date>
</imprint>
</series>
</biblStruct>
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</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<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>
</keywords>
<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>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr">
<term>Cathepsines</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en">
<term>Betacoronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<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>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Betacoronavirus</term>
<term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<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>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<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>
</keywords>
<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>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<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>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="Par1">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.</p>
</div>
</front>
<back>
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<affiliations>
<list>
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<li>République populaire de Chine</li>
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<li>Pékin</li>
</settlement>
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</noRegion>
<name sortKey="Chen, Jieyong" sort="Chen, Jieyong" uniqKey="Chen J" first="Jieyong" last="Chen">Jieyong Chen</name>
<name sortKey="Chen, Ting" sort="Chen, Ting" uniqKey="Chen T" first="Ting" last="Chen">Ting Chen</name>
<name sortKey="Chen, Xing" sort="Chen, Xing" uniqKey="Chen X" first="Xing" last="Chen">Xing Chen</name>
<name sortKey="Guo, Li" sort="Guo, Li" uniqKey="Guo L" first="Li" last="Guo">Li Guo</name>
<name sortKey="Guo, Ruixuan" sort="Guo, Ruixuan" uniqKey="Guo R" first="Ruixuan" last="Guo">Ruixuan Guo</name>
<name sortKey="Hu, Jiaxin" sort="Hu, Jiaxin" uniqKey="Hu J" first="Jiaxin" last="Hu">Jiaxin Hu</name>
<name sortKey="Hu, Keping" sort="Hu, Keping" uniqKey="Hu K" first="Keping" last="Hu">Keping Hu</name>
<name sortKey="Jin, Qi" sort="Jin, Qi" uniqKey="Jin Q" first="Qi" last="Jin">Qi Jin</name>
<name sortKey="Lei, Xiaobo" sort="Lei, Xiaobo" uniqKey="Lei X" first="Xiaobo" last="Lei">Xiaobo Lei</name>
<name sortKey="Li, Pei" sort="Li, Pei" uniqKey="Li P" first="Pei" last="Li">Pei Li</name>
<name sortKey="Liu, Yan" sort="Liu, Yan" uniqKey="Liu Y" first="Yan" last="Liu">Yan Liu</name>
<name sortKey="Mi, Dan" sort="Mi, Dan" uniqKey="Mi D" first="Dan" last="Mi">Dan Mi</name>
<name sortKey="Mu, Zhixia" sort="Mu, Zhixia" uniqKey="Mu Z" first="Zhixia" last="Mu">Zhixia Mu</name>
<name sortKey="Qian, Zhaohui" sort="Qian, Zhaohui" uniqKey="Qian Z" first="Zhaohui" last="Qian">Zhaohui Qian</name>
<name sortKey="Ren, Lili" sort="Ren, Lili" uniqKey="Ren L" first="Lili" last="Ren">Lili Ren</name>
<name sortKey="Wang, Jianwei" sort="Wang, Jianwei" uniqKey="Wang J" first="Jianwei" last="Wang">Jianwei Wang</name>
<name sortKey="Xiang, Zichun" sort="Xiang, Zichun" uniqKey="Xiang Z" first="Zichun" last="Xiang">Zichun Xiang</name>
</country>
</tree>
</affiliations>
</record>

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