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

Rui Shi; Chao Shan; Xiaomin Duan; Zhihai Chen; Peipei Liu; Jinwen Song; Tao Song; Xiaoshan Bi; Chao Han; Lianao Wu; Ge Gao; Xue Hu; Yanan Zhang; Zhou Tong; Weijin Huang; William Jun Liu; Guizhen Wu; Bo Zhang; Lan Wang; Jianxun Qi; Hui Feng; Fu-Sheng Wang; Qihui Wang; George Fu Gao; Zhiming Yuan; Jinghua Yan

doi:10.1038/s41586-020-2381-y

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

Nature. 2020 Aug;584(7819):120-124. doi: 10.1038/s41586-020-2381-y. Epub 2020 May 26.

Authors

Rui Shi^#^{1

2}, Chao Shan^#³, Xiaomin Duan^#^{1

2}, Zhihai Chen^#⁴, Peipei Liu^#⁵, Jinwen Song^#⁶, Tao Song^{1

7

8}, Xiaoshan Bi^{1

9}, Chao Han^{1

2}, Lianao Wu^{9

10}, Ge Gao³, Xue Hu³, Yanan Zhang³, Zhou Tong^{1

10}, Weijin Huang¹¹, William Jun Liu⁵, Guizhen Wu⁵, Bo Zhang³, Lan Wang¹¹, Jianxun Qi^{10

12}, Hui Feng¹³, Fu-Sheng Wang¹⁴, Qihui Wang^{15

16

17}, George Fu Gao¹⁸, Zhiming Yuan¹⁹, Jinghua Yan^{20

21

22}

Affiliations

¹ CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
² University of Chinese Academy of Sciences, Beijing, China.
³ Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
⁴ Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
⁵ NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
⁶ Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
⁷ Shanxi Academy of Advanced Research and Innovation, Taiyuan, China.
⁸ College of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, China.
⁹ Institute of Physical Science and Information, Anhui University, Hefei, China.
¹⁰ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
¹¹ Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, China.
¹² Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
¹³ Shanghai Junshi Biosciences Co. Ltd, Shanghai, China.
¹⁴ Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. fswang302@163.com.
¹⁵ CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. wangqihui@im.ac.cn.
¹⁶ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. wangqihui@im.ac.cn.
¹⁷ Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China. wangqihui@im.ac.cn.
¹⁸ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. gaof@im.ac.cn.
¹⁹ Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. yzm@wh.iov.cn.
²⁰ CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. yanjh@im.ac.cn.
²¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. yanjh@im.ac.cn.
²² Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China. yanjh@im.ac.cn.

^# Contributed equally.

PMID: 32454512
DOI: 10.1038/s41586-020-2381-y

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme 2
Animals
Antibodies, Neutralizing / chemistry
Antibodies, Neutralizing / immunology*
Antibodies, Neutralizing / pharmacology
Antibodies, Viral / chemistry
Antibodies, Viral / immunology*
Antibodies, Viral / pharmacology
Betacoronavirus / chemistry
Betacoronavirus / immunology*
Binding, Competitive
COVID-19
Cell Line
Chlorocebus aethiops
Coronavirus Infections / immunology*
Coronavirus Infections / virology*
Crystallization
Crystallography, X-Ray
Female
Humans
In Vitro Techniques
Macaca mulatta / immunology
Macaca mulatta / virology
Male
Models, Molecular
Neutralization Tests
Pandemics
Peptidyl-Dipeptidase A / chemistry
Peptidyl-Dipeptidase A / metabolism
Pneumonia, Viral / immunology*
Pneumonia, Viral / virology*
Protein Binding / drug effects
SARS-CoV-2
Spike Glycoprotein, Coronavirus / antagonists & inhibitors
Spike Glycoprotein, Coronavirus / chemistry*
Spike Glycoprotein, Coronavirus / immunology*
Spike Glycoprotein, Coronavirus / metabolism
Vero Cells
Viral Load / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Peptidyl-Dipeptidase A
ACE2 protein, human
Angiotensin-Converting Enzyme 2