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A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2.
Nature. 2020 Aug; 584(7819):120-124.Nat

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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Publisher Full Text (DOI)

Authors+Show Affiliations

Shi R
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. University of Chinese Academy of Sciences, Beijing, China.
Shan C
Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Duan X
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. University of Chinese Academy of Sciences, Beijing, China.
Chen Z
Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Liu P
NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Song J
Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
Song T
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. Shanxi Academy of Advanced Research and Innovation, Taiyuan, China. College of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, China.
Bi X
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. Institute of Physical Science and Information, Anhui University, Hefei, China.
Han C
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. University of Chinese Academy of Sciences, Beijing, China.
Wu L
Institute of Physical Science and Information, Anhui University, Hefei, China. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Gao G
Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Hu X
Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Zhang Y
Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Tong Z
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Huang W
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.
Liu WJ
NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Wu G
NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Zhang B
Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Wang L
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.
Qi J
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
Feng H
Shanghai Junshi Biosciences Co. Ltd, Shanghai, China.
Wang FS
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.
Wang Q
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. wangqihui@im.ac.cn. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. wangqihui@im.ac.cn. Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China. wangqihui@im.ac.cn.
Gao GF
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. gaof@im.ac.cn.
Yuan Z
Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. yzm@wh.iov.cn.
Yan J
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. yanjh@im.ac.cn. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. yanjh@im.ac.cn. Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China. yanjh@im.ac.cn.

MeSH

Angiotensin-Converting Enzyme 2AnimalsAntibodies, NeutralizingAntibodies, ViralBetacoronavirusBinding, CompetitiveCOVID-19Cell LineChlorocebus aethiopsCoronavirus InfectionsCrystallizationCrystallography, X-RayFemaleHumansIn Vitro TechniquesMacaca mulattaMaleModels, MolecularNeutralization TestsPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein BindingSARS-CoV-2Spike Glycoprotein, CoronavirusVero CellsViral Load

Pub Type(s)

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

Language

eng

PubMed ID

32454512

Citation

Shi, Rui, et al. "A Human Neutralizing Antibody Targets the Receptor-binding Site of SARS-CoV-2." Nature, vol. 584, no. 7819, 2020, pp. 120-124.
Shi R, Shan C, Duan X, et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature. 2020;584(7819):120-124.
Shi, R., Shan, C., Duan, X., Chen, Z., Liu, P., Song, J., Song, T., Bi, X., Han, C., Wu, L., Gao, G., Hu, X., Zhang, Y., Tong, Z., Huang, W., Liu, W. J., Wu, G., Zhang, B., Wang, L., ... Yan, J. (2020). A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature, 584(7819), 120-124. https://doi.org/10.1038/s41586-020-2381-y
Shi R, et al. A Human Neutralizing Antibody Targets the Receptor-binding Site of SARS-CoV-2. Nature. 2020;584(7819):120-124. PubMed PMID: 32454512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. AU - Shi,Rui, AU - Shan,Chao, AU - Duan,Xiaomin, AU - Chen,Zhihai, AU - Liu,Peipei, AU - Song,Jinwen, AU - Song,Tao, AU - Bi,Xiaoshan, AU - Han,Chao, AU - Wu,Lianao, AU - Gao,Ge, AU - Hu,Xue, AU - Zhang,Yanan, AU - Tong,Zhou, AU - Huang,Weijin, AU - Liu,William Jun, AU - Wu,Guizhen, AU - Zhang,Bo, AU - Wang,Lan, AU - Qi,Jianxun, AU - Feng,Hui, AU - Wang,Fu-Sheng, AU - Wang,Qihui, AU - Gao,George Fu, AU - Yuan,Zhiming, AU - Yan,Jinghua, Y1 - 2020/05/26/ PY - 2020/4/2/received PY - 2020/5/19/accepted PY - 2020/5/27/pubmed PY - 2020/8/13/medline PY - 2020/5/27/entrez SP - 120 EP - 124 JF - Nature JO - Nature VL - 584 IS - 7819 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32454512/A_human_neutralizing_antibody_targets_the_receptor_binding_site_of_SARS_CoV_2_ DB - PRIME DP - Unbound Medicine ER -