Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies

Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a ma...

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Veröffentlicht in:Cellular & molecular immunology 2020-06, Vol.17 (6), p.621-630
Hauptverfasser: Yi, Chunyan, Sun, Xiaoyu, Ye, Jing, Ding, Longfei, Liu, Meiqin, Yang, Zhuo, Lu, Xiao, Zhang, Yaguang, Ma, Liyang, Gu, Wangpeng, Qu, Aidong, Xu, Jianqing, Shi, Zhengli, Ling, Zhiyang, Sun, Bing
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container_end_page 630
container_issue 6
container_start_page 621
container_title Cellular & molecular immunology
container_volume 17
creator Yi, Chunyan
Sun, Xiaoyu
Ye, Jing
Ding, Longfei
Liu, Meiqin
Yang, Zhuo
Lu, Xiao
Zhang, Yaguang
Ma, Liyang
Gu, Wangpeng
Qu, Aidong
Xu, Jianqing
Shi, Zhengli
Ling, Zhiyang
Sun, Bing
description Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.
doi_str_mv 10.1038/s41423-020-0458-z
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The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. 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molecular immunology</jtitle><stitle>Cell Mol Immunol</stitle><addtitle>Cell Mol Immunol</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>17</volume><issue>6</issue><spage>621</spage><epage>630</epage><pages>621-630</pages><issn>1672-7681</issn><eissn>2042-0226</eissn><abstract>Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. 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Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32415260</pmid><doi>10.1038/s41423-020-0458-z</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-2417-6516</orcidid><orcidid>https://orcid.org/0000-0003-0896-9273</orcidid><oa>free_for_read</oa></addata></record>
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subjects 631/250/21/2153
631/250/251/1567
631/250/254
ACE2
Amino Acid Motifs
Amino acids
Angiotensin
Angiotensin-Converting Enzyme 2
Animals
Antibodies
Antibodies, Monoclonal - immunology
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Antibodies, Viral - metabolism
Betacoronavirus - immunology
Betacoronavirus - metabolism
Betacoronavirus - physiology
Binding Sites
Biomedical and Life Sciences
Biomedicine
Coronaviruses
COVID-19
Cross Reactions
Epitopes
HEK293 Cells
Humans
Immunization
Immunology
Male
Medical Microbiology
Mice
Mice, Inbred C57BL
Microbiology
Monoclonal antibodies
Pandemics
Peptidyl-dipeptidase A
Peptidyl-Dipeptidase A - metabolism
Protein Interaction Domains and Motifs - immunology
Public health
Receptors, Coronavirus
Receptors, Virus - metabolism
SARS Virus - immunology
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - immunology
Spike Glycoprotein, Coronavirus - metabolism
Spike protein
Vaccine
Virus Internalization
title Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies
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