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

doi:10.1038/s41586-020-2381-y

. 2020 Aug;584(7819):120-124.

doi: 10.1038/s41586-020-2381-y. Epub 2020 May 26.

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

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

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

Rui Shi et al. Nature. 2020 Aug.

. 2020 Aug;584(7819):120-124.

doi: 10.1038/s41586-020-2381-y. Epub 2020 May 26.

Authors

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.

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References

1. Tan, W. et al. Notes from the field: a novel coronavirus genome identified in a cluster of pneumonia cases – Wuhan, China 2019–2020. China CDC Weekly 2, 61–62 (2020). - DOI
1. The 2019-nCoV Outbreak Joint Field Epidemiology Investigation Team & Li, Q. Notes from the field: an outbreak of NCIP (2019-nCoV) infection in China – Wuhan, Hubei province, 2019–2020. China CDC Weekly 2, 79–80 (2020).
1. Wang, C., Horby, P. W., Hayden, F. G. & Gao, G. F. A novel coronavirus outbreak of global health concern. Lancet 395, 470–473 (2020). - DOI
1. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 5, 536–544 (2020). - DOI
1. Gao, G. F. From “A”IV to “Z”IKV: attacks from emerging and re-emerging pathogens. Cell 172, 1157–1159 (2018). - DOI

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[1] Tan, W. et al. Notes from the field: a novel coronavirus genome identified in a cluster of pneumonia cases – Wuhan, China 2019–2020. China CDC Weekly 2, 61–62 (2020). - DOI

[2] Tan, W. et al. Notes from the field: a novel coronavirus genome identified in a cluster of pneumonia cases – Wuhan, China 2019–2020. China CDC Weekly 2, 61–62 (2020). - DOI

[3] The 2019-nCoV Outbreak Joint Field Epidemiology Investigation Team & Li, Q. Notes from the field: an outbreak of NCIP (2019-nCoV) infection in China – Wuhan, Hubei province, 2019–2020. China CDC Weekly 2, 79–80 (2020).

[4] The 2019-nCoV Outbreak Joint Field Epidemiology Investigation Team & Li, Q. Notes from the field: an outbreak of NCIP (2019-nCoV) infection in China – Wuhan, Hubei province, 2019–2020. China CDC Weekly 2, 79–80 (2020).

[5] Wang, C., Horby, P. W., Hayden, F. G. & Gao, G. F. A novel coronavirus outbreak of global health concern. Lancet 395, 470–473 (2020). - DOI

[6] Wang, C., Horby, P. W., Hayden, F. G. & Gao, G. F. A novel coronavirus outbreak of global health concern. Lancet 395, 470–473 (2020). - DOI

[7] Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 5, 536–544 (2020). - DOI

[8] Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 5, 536–544 (2020). - DOI

[9] Gao, G. F. From “A”IV to “Z”IKV: attacks from emerging and re-emerging pathogens. Cell 172, 1157–1159 (2018). - DOI

[10] Gao, G. F. From “A”IV to “Z”IKV: attacks from emerging and re-emerging pathogens. Cell 172, 1157–1159 (2018). - DOI

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

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

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