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Structural basis of nanobodies neutralizing SARS-CoV-2 variants

文献类型：期刊论文

作者Shi, Zhenzhong6,7; Li, Xiyang5; Wang, Lu7; Sun, Zengchao6,7; Zhang, Haiwei4; Chen, Xiaochen7; Cui, Qianqian3; Qiao, Huarui6; Lan, Zhongyun6; Zhang, Xin6
刊名STRUCTURE
出版日期2022-05-05
卷号30期号:5页码:707-+
ISSN号0969-2126
DOI10.1016/j.str.2022.02.011
通讯作者Xu, Jianfeng(jfxu@shou.edu.cn) ; Gong, Rui(gongr@wh.iov.cn) ; Fan, Chengpeng(chengpeng.fan@whu.edu.cn) ; Geng, Yong(gengyong@simm.ac.cn)
英文摘要Because of the evolutionary variants of SARS-CoV-2, development of broad-spectrum neutralizing antibodies resilient to virus escape is urgently needed. We identified a group of high-affinity nanobodies from camels immunized with receptor-binding domain (RBD) of SARS-CoV-2 spike protein and resolved the structures of two non-competing nanobodies (NB1A7 and NB1B11) in complex with RBD using X-ray crystallography. The structures show that NB1A7 targets the highly conserved cryptic epitope shared by SARS-CoV-2 variants and some other coronaviruses and blocks ACE2 receptor attachment of the spike protein, and NB1B11 epitope overlaps with the contacting surface of ACE2 and is different from the binding site of NB1A7. These two nanobodies were covalently linked into multivalent and bi-paratopic formats, which significantly improved the avidity and neutralization potency and may further inhibit viral escape. The results contribute to the structure-guided design of antibodies against future variants of SARS-CoV-2 virus to combat coronavirus epidemics and pandemics.
WOS关键词ANTIBODIES ; COCKTAIL
资助项目National Natural Science Foundation of China[31670743] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040326] ; Science and Technology Commission of Shanghai Municipality[18JC1415400] ; Joint Research Fund for Overseas, Hong Kong and Macao Scholars[81628013] ; Natural Science Foundation of Shanghai[16ZR1442900] ; National Science Foundation for Young Scholar projects[81803599] ; Zhejiang University COVID-19 Special Project[2020XGZX092] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[CASIMM0120164013] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1606YZZ-06] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1601KF-06] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[55201631121116101] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[55201631121108000] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[5112345601] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[2015123456005]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种英语
WOS记录号WOS:000799220200007
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/301181]  
专题新药研究国家重点实验室
通讯作者Xu, Jianfeng; Gong, Rui; Fan, Chengpeng; Geng, Yong
作者单位1.Wuhan Univ, Sch Basic Med Sci, Wuhan 430071, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Shanghai Univ, Coll Sci, Shanghai 200444, Peoples R China
4.Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, Ctr Emerging Infect Dis,CAS Key Lab Special Patho, 44 Xiao Hong Shan, Wuhan 430071, Hubei, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China
6.Shanghai Ocean Univ, Coll Food Sci & Technol, Dept Biopharmaceut, Shanghai 201306, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Stake Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Shi, Zhenzhong,Li, Xiyang,Wang, Lu,et al. Structural basis of nanobodies neutralizing SARS-CoV-2 variants[J]. STRUCTURE,2022,30(5):707-+.
APA Shi, Zhenzhong.,Li, Xiyang.,Wang, Lu.,Sun, Zengchao.,Zhang, Haiwei.,...&Geng, Yong.(2022).Structural basis of nanobodies neutralizing SARS-CoV-2 variants.STRUCTURE,30(5),707-+.
MLA Shi, Zhenzhong,et al."Structural basis of nanobodies neutralizing SARS-CoV-2 variants".STRUCTURE 30.5(2022):707-+.

入库方式： OAI收割

来源：上海药物研究所

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