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Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins

文献类型：期刊论文

作者Xu, Youwei7; Wu, Canrong7; Cao, Xiaodan6; Gu, Chunyin6; Liu, Heng7; Jiang, Mengting5,7; Wang, Xiaoxi7; Yuan, Qingning3,7; Wu, Kai3,7; Liu, Jia6
刊名CELL RESEARCH
出版日期2022-05-31
页码12
ISSN号1001-0602
DOI10.1038/s41422-022-00672-4
通讯作者Deng, Su-Jun(dengsujun@jemincare.com) ; Xu, H. Eric(eric.xu@simm.ac.cn) ; Yin, Wanchao(wcyin@simm.ac.cn)
英文摘要The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies show that the Omicron BA.2 spike trimer exhibits 11-fold and 2-fold higher potency in binding to human ACE2 than the spike trimer from the wildtype (WT) and Omicron BA.1 strains. The structure of the BA.2 spike trimer complexed with human ACE2 reveals that all three receptor-binding domains (RBDs) in the spike trimer are in open conformation, ready for ACE2 binding, thus providing a basis for the increased infectivity of the BA.2 strain. JMB2002, a therapeutic antibody that was shown to efficiently inhibit Omicron BA.1, also shows potent neutralization activities against Omicron BA.2. In addition, both BA.1 and BA.2 spike trimers are able to bind to mouse ACE2 with high potency. In contrast, the WT spike trimer binds well to cat ACE2 but not to mouse ACE2. The structures of both BA.1 and BA.2 spike trimer bound to mouse ACE2 reveal the basis for their high affinity interactions. Together, these results suggest a possible evolution pathway for Omicron BA.1 and BA.2 variants via a human-cat-mouse-human circle, which could have important implications in establishing an effective strategy for combating SARS-CoV-2 viral infections.
WOS关键词MODEL
资助项目Ministry of Science and Technology (China)[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Shanghai Municipal Science and Technology Major Project ; CAS Strategic Priority Research Program[XDB37030103] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[32171189] ; National Natural Science Foundation of China[81902085] ; Youth Innovation Promotion Association of CAS[2021278] ; National Science Fund for Excellent Young Scholars[82122067] ; Key tasks of the Lingang Laboratory[LG202103-03-05] ; Key tasks of the Lingang Laboratory[LG202101-01-03] ; China Postdoctoral Science Foundation[2021M703342] ; Shanghai Post-doctoral Excellence Program[2021429] ; High-level Innovative Research Institute from Department of Science and Technology of Guangdong Province[2021B0909050003] ; Sanofi Scholarship Program ; High-level new R&D institute from Department of Science and Technology of Guangdong Province[2019B090904008]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000803910300001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/301172]  
专题中国科学院上海药物研究所
通讯作者Deng, Su-Jun; Xu, H. Eric; Yin, Wanchao
作者单位1.Shanghai Inst Mat Medica, Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Medica, Shanghai Adv Electron Microscope Ctr, Shanghai, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Adv Electron Microscope Ctr, Shanghai, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China
6.Shanghai Jemincare Pharmaceut Co Ltd, Shanghai, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Youwei,Wu, Canrong,Cao, Xiaodan,et al. Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins[J]. CELL RESEARCH,2022:12.
APA Xu, Youwei.,Wu, Canrong.,Cao, Xiaodan.,Gu, Chunyin.,Liu, Heng.,...&Yin, Wanchao.(2022).Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins.CELL RESEARCH,12.
MLA Xu, Youwei,et al."Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins".CELL RESEARCH (2022):12.

入库方式： OAI收割

来源：上海药物研究所

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