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

doi:10.1038/s41423-020-0458-z

	Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies
	Yi, Chunyan 1; Sun, Xiaoyu 1; Ye, Jing1,2 ; Ding, Longfei 3; Liu, Meiqin 4; Yang, Zhuo 1; Lu, Xiao2 ; Zhang, Yaguang 1; Ma, Liyang 1; Gu, Wangpeng 1; Qu, Aidong 5; Xu, Jianqing 3; Shi, Zhengli 4; Ling, Zhiyang 1; Sun, Bing1,2
	2020-06
发表期刊	CELLULAR & MOLECULAR IMMUNOLOGY
ISSN	1672-7681
EISSN	2042-0226
发表状态	已发表
DOI	10.1038/s41423-020-0458-z
摘要	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.
关键词	SARS-CoV-2 spike protein receptor binding motif cross-neutralizing antibody substitution mutation
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[82041015] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19000000] ; Key International Partnership Program of the Chinese Academy of Sciences[153D31KYSB20180055] ; National Major Science and Technology Projects of China[2018ZX10301403]
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000533048500003
出版者	NATURE PUBLISHING GROUP
WOS关键词	SARS CORONAVIRUS ; DOMAIN
原始文献类型	Article ; Early Access
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/121088
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_孙兵组生命科学与技术学院_博士生
通讯作者	Shi, Zhengli; Ling, Zhiyang; Sun, Bing
作者单位	1.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Fudan Univ, Shanghai Publ Hlth Clin Ctr, Shanghai 201508, Peoples R China 4.Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan Inst Virol, Key Lab Special Pathogens, Wuhan 430071, Peoples R China 5.Shanghai Inst Biol Prod, Shanghai 200052, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yi, Chunyan,Sun, Xiaoyu,Ye, Jing,et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies[J]. CELLULAR & MOLECULAR IMMUNOLOGY,2020.
APA	Yi, Chunyan.,Sun, Xiaoyu.,Ye, Jing.,Ding, Longfei.,Liu, Meiqin.,...&Sun, Bing.(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.
MLA	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 (2020).