Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist circulating variants

被引：58

作者：

Li, Tingting ^{[1
,2
]}

Xue, Wenhui ^{[1
,2
]}

Zheng, Qingbing ^{[1
,2
]}

Song, Shuo ^{[3
,4
]}

Yang, Chuanlai ^{[1
,2
]}

Xiong, Hualong ^{[1
,2
]}

Zhang, Sibo ^{[1
,2
]}

Hong, Minqing ^{[1
,2
]}

Zhang, Yali ^{[1
,2
]}

Yu, Hai ^{[1
,2
]}

Zhang, Yuyun ^{[1
,2
]}

Sun, Hui ^{[1
,2
]}

Huang, Yang ^{[1
,2
]}

Deng, Tingting ^{[1
,2
]}

Chi, Xin ^{[1
,2
]}

Li, Jinjin ^{[1
,2
]}

Wang, Shaojuan ^{[1
,2
]}

Zhou, Lizhi ^{[1
,2
]}

Chen, Tingting ^{[1
,2
]}

Wang, Yingbin ^{[1
,2
]}

Cheng, Tong ^{[1
,2
]}

Zhang, Tianying ^{[1
,2
]}

Yuan, Quan ^{[1
,2
]}

Zhao, Qinjian ^{[1
,2
]}

Zhang, Jun ^{[1
,2
]}

McLellan, Jason S. ^{[5
]}

Zhou, Z. Hong ^{[6
,7
]}

Zhang, Zheng ^{[3
,4
]}

Li, Shaowei ^{[1
,2
]}

Gu, Ying ^{[1
,2
]}

Xia, Ningshao ^{[1
,2
,8
]}

机构：

[1] Xiamen Univ, Sch Life Sci, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Fujian, Peoples R China

[2] Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Xiamen 361102, Fujian, Peoples R China

[3] Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Inst Hepatol, Shenzhen 518112, Guangdong, Peoples R China

[4] Southern Univ Sci & Technol, Sch Med, Affiliated Hosp 2, Shenzhen 518112, Guangdong, Peoples R China

[5] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA

[6] Univ Calif Los Angeles, Calif NanoSyst Inst CNSI, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[8] Chinese Acad Med Sci, Res Unit Frontier Technol Struct Vaccinol, Xiamen 518112, Fujian, Peoples R China

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

基金：

中国国家自然科学基金;

关键词：

CRYO-EM STRUCTURE; INFLUENZA; INFECTION; PROTECT; DOMAIN; VIRUS; SPIKE; IGG;

D O I：

10.1038/s41467-021-25997-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses' receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines. Antibodies (Abs) targeting highly conserved epitopes are important tools against emerging virus variants. Here, the authors characterize Abs that recognize a cryptic epitope in the receptor-binding domain of SARS-CoV-2 spike that is well conserved and show that these Abs can neutralize several variants of concerns.

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页数：12

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