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Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies.
Cell Mol Immunol. 2020 06; 17(6):621-630.CM

Abstract

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.

Authors+Show Affiliations

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China. School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.Shanghai Public Health Clinical Center, Fudan University, 201508, Shanghai, China.Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, 430071, Wuhan, China.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China.School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China.Shanghai Institute of Biological Products, 200052, Shanghai, China.Shanghai Public Health Clinical Center, Fudan University, 201508, Shanghai, China.Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, 430071, Wuhan, China. zlshi@wh.iov.cn.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China. lingzhiyang@sibs.ac.cn.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China. bsun@sibs.ac.cn. School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China. bsun@sibs.ac.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32415260

Citation

Yi, Chunyan, et al. "Key Residues of the Receptor Binding Motif in the Spike Protein of SARS-CoV-2 That Interact With ACE2 and Neutralizing Antibodies." Cellular & Molecular Immunology, vol. 17, no. 6, 2020, pp. 621-630.
Yi C, Sun X, Ye J, et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol. 2020;17(6):621-630.
Yi, C., Sun, X., Ye, J., Ding, L., Liu, M., Yang, Z., Lu, X., Zhang, Y., Ma, L., Gu, W., Qu, A., Xu, J., Shi, Z., Ling, Z., & Sun, B. (2020). Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cellular & Molecular Immunology, 17(6), 621-630. https://doi.org/10.1038/s41423-020-0458-z
Yi C, et al. Key Residues of the Receptor Binding Motif in the Spike Protein of SARS-CoV-2 That Interact With ACE2 and Neutralizing Antibodies. Cell Mol Immunol. 2020;17(6):621-630. PubMed PMID: 32415260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. AU - Yi,Chunyan, AU - Sun,Xiaoyu, AU - Ye,Jing, AU - Ding,Longfei, AU - Liu,Meiqin, AU - Yang,Zhuo, AU - Lu,Xiao, AU - Zhang,Yaguang, AU - Ma,Liyang, AU - Gu,Wangpeng, AU - Qu,Aidong, AU - Xu,Jianqing, AU - Shi,Zhengli, AU - Ling,Zhiyang, AU - Sun,Bing, Y1 - 2020/05/15/ PY - 2020/04/13/received PY - 2020/04/29/accepted PY - 2020/5/18/pubmed PY - 2020/6/17/medline PY - 2020/5/17/entrez KW - SARS-CoV-2 KW - cross-neutralizing antibody KW - receptor binding motif KW - spike protein KW - substitution mutation SP - 621 EP - 630 JF - Cellular & molecular immunology JO - Cell Mol Immunol VL - 17 IS - 6 N2 - 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. SN - 2042-0226 UR - https://www.unboundmedicine.com/medline/citation/32415260/Key_residues_of_the_receptor_binding_motif_in_the_spike_protein_of_SARS_CoV_2_that_interact_with_ACE2_and_neutralizing_antibodies_ L2 - https://doi.org/10.1038/s41423-020-0458-z DB - PRIME DP - Unbound Medicine ER -