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Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.

Identifieur interne : 000206 ( Main/Exploration ); précédent : 000205; suivant : 000207

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.

Auteurs : Qihui Wang [République populaire de Chine] ; Yanfang Zhang [République populaire de Chine] ; Lili Wu [République populaire de Chine] ; Sheng Niu [République populaire de Chine] ; Chunli Song [République populaire de Chine] ; Zengyuan Zhang [République populaire de Chine] ; Guangwen Lu [République populaire de Chine] ; Chengpeng Qiao [République populaire de Chine] ; Yu Hu [République populaire de Chine] ; Kwok-Yung Yuen [République populaire de Chine] ; Qisheng Wang [République populaire de Chine] ; Huan Zhou [République populaire de Chine] ; Jinghua Yan [République populaire de Chine] ; Jianxun Qi [République populaire de Chine]

Source :

RBID : pubmed:32275855

Abstract

The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.

DOI: 10.1016/j.cell.2020.03.045
PubMed: 32275855


Affiliations:


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<wicri:regionArea>CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Institute of Physical Science and Information, Anhui University, Hefei 230039, China; College of Life Science, University of the Chinese Academy of Sciences, Beijing 100049</wicri:regionArea>
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<settlement type="city">Pékin</settlement>
</placeName>
</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:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jxqi@im.ac.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049</wicri:regionArea>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Cell</title>
<idno type="eISSN">1097-4172</idno>
<imprint>
<date when="2020" type="published">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
<region>
<li>Anhui</li>
</region>
<settlement>
<li>Hefei</li>
<li>Pékin</li>
<li>Tianjin</li>
</settlement>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Wang, Qihui" sort="Wang, Qihui" uniqKey="Wang Q" first="Qihui" last="Wang">Qihui Wang</name>
</noRegion>
<name sortKey="Hu, Yu" sort="Hu, Yu" uniqKey="Hu Y" first="Yu" last="Hu">Yu Hu</name>
<name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name>
<name sortKey="Niu, Sheng" sort="Niu, Sheng" uniqKey="Niu S" first="Sheng" last="Niu">Sheng Niu</name>
<name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<name sortKey="Qiao, Chengpeng" sort="Qiao, Chengpeng" uniqKey="Qiao C" first="Chengpeng" last="Qiao">Chengpeng Qiao</name>
<name sortKey="Song, Chunli" sort="Song, Chunli" uniqKey="Song C" first="Chunli" last="Song">Chunli Song</name>
<name sortKey="Wang, Qisheng" sort="Wang, Qisheng" uniqKey="Wang Q" first="Qisheng" last="Wang">Qisheng Wang</name>
<name sortKey="Wu, Lili" sort="Wu, Lili" uniqKey="Wu L" first="Lili" last="Wu">Lili Wu</name>
<name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</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, Yanfang" sort="Zhang, Yanfang" uniqKey="Zhang Y" first="Yanfang" last="Zhang">Yanfang Zhang</name>
<name sortKey="Zhang, Zengyuan" sort="Zhang, Zengyuan" uniqKey="Zhang Z" first="Zengyuan" last="Zhang">Zengyuan Zhang</name>
<name sortKey="Zhou, Huan" sort="Zhou, Huan" uniqKey="Zhou H" first="Huan" last="Zhou">Huan Zhou</name>
</country>
</tree>
</affiliations>
</record>

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