A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2

被引：1028

作者：

Shi, Rui ^{[1
,2
]}

Shan, Chao ^{[3
]}

Duan, Xiaomin ^{[1
,2
]}

Chen, Zhihai ^{[4
]}

Liu, Peipei ^{[5
]}

Song, Jinwen ^{[6
]}

Song, Tao ^{[1
,7
,8
]}

Bi, Xiaoshan ^{[1
,9
]}

Han, Chao ^{[1
,2
]}

Wu, Lianao ^{[9
,10
]}

Gao, Ge ^{[3
]}

Hu, Xue ^{[3
]}

Zhang, Yanan ^{[3
]}

Tong, Zhou ^{[1
,10
]}

Huang, Weijin ^{[11
]}

Liu, William Jun ^{[5
]}

Wu, Guizhen ^{[5
]}

Zhang, Bo ^{[3
]}

Wang, Lan ^{[11
]}

Qi, Jianxun ^{[10
,12
]}

Feng, Hui ^{[13
]}

Wang, Fu-Sheng ^{[6
]}

Wang, Qihui ^{[1
,10
,12
]}

Gao, George Fu ^{[10
]}

Yuan, Zhiming ^{[3
]}

Yan, Jinghua ^{[1
,10
,12
]}

机构：

[1] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Microbial Physiol & Metab Engn, Beijing, Peoples R China

[2] Univ Chinese Acad Sci, Beijing, Peoples R China

[3] Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, Wuhan, Peoples R China

[4] Capital Med Univ, Beijing Ditan Hosp, Ctr Infect Dis, Beijing, Peoples R China

[5] Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, NHC Key Lab Biosafety, Beijing, Peoples R China

[6] Peoples Liberat Army Gen Hosp, Natl Clin Res Ctr Infect Dis, Med Ctr 5, Treatment & Res Ctr Infect Dis, Beijing, Peoples R China

[7] Shanxi Acad Adv Res & Innovat, Taiyuan, Peoples R China

[8] Hebei Normal Univ Sci & Technol, Coll Anim Sci & Technol, Qinhuangdao, Hebei, Peoples R China

[9] Anhui Univ, Inst Phys Sci & Informat, Hefei, Peoples R China

[10] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China

[11] Natl Inst Food & Drug Control, Minist Hlth Res Qual & Standardizat Biotech Prod, Key Lab, Beijing, Peoples R China

[12] Univ Chinese Acad Sci, Savaid Med Sch, Beijing, Peoples R China

[13] Shanghai Junshi Biosci Co Ltd, Shanghai, Peoples R China

来源：

NATURE | 2020年 / 584卷 / 7819期

基金：

中国国家自然科学基金;

关键词：

SARS-COV; SPIKE PROTEIN; CORONAVIRUS; FEATURES; ENTRY;

D O I：

10.1038/s41586-020-2381-y

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：

An outbreak of coronavirus disease 2019 (COVID-19)(1-3), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(4), has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic. Two monoclonal antibodies isolated from a patient with COVID-19 are shown to interfere with SARS-CoV-2-receptor binding, and one displays potent action against this virus in vitro and in a rhesus macaque model.

引用

页码：120 / +

页数：16

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