Structural basis of nanobodies neutralizing SARS-CoV-2 variants

被引：10

作者：

Shi, Zhenzhong ^{[1
,2
]}

Li, Xiyang ^{[3
]}

Wang, Lu ^{[1
]}

Sun, Zengchao ^{[1
,2
]}

Zhang, Haiwei ^{[4
]}

Chen, Xiaochen ^{[1
]}

Cui, Qianqian ^{[5
]}

Qiao, Huarui ^{[2
]}

Lan, Zhongyun ^{[2
]}

Zhang, Xin ^{[2
]}

Li, Xianheng ^{[2
]}

Li, Lingyun ^{[1
]}

Xu, Jianfeng ^{[2
]}

Gong, Rui ^{[4
]}

Fan, Chengpeng ^{[6
]}

Geng, Yong ^{[1
,3
,7
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Stake Key Lab Drug Res, Shanghai 201203, Peoples R China

[2] Shanghai Ocean Univ, Coll Food Sci & Technol, Dept Biopharmaceut, Shanghai 201306, Peoples R China

[3] Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, 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] Shanghai Univ, Coll Sci, Shanghai 200444, Peoples R China

[6] Wuhan Univ, Sch Basic Med Sci, Wuhan 430071, Peoples R China

[7] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

来源：

STRUCTURE | 2022年 / 30卷 / 05期

基金：

上海市自然科学基金; 美国国家科学基金会; 中国国家自然科学基金;

关键词：

ANTIBODIES; COCKTAIL;

D O I：

10.1016/j.str.2022.02.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页码：707 / +

页数：20

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