A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2
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...
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| Published in | Nature (London) Vol. 584; no. 7819; pp. 120 - 124 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
06.08.2020
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| 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.
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. |
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| AbstractList | 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 oftwo 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. An outbreak of coronavirus disease 2019 (COVID-19) , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) , 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. 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. 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.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. |
| Author | Zhang, Yanan Wang, Lan Hu, Xue Liu, Peipei Song, Tao Huang, Weijin Gao, George Fu Tong, Zhou Zhang, Bo Duan, Xiaomin Shan, Chao Wang, Fu-Sheng Liu, William Jun Bi, Xiaoshan Feng, Hui Han, Chao Shi, Rui Song, Jinwen Wang, Qihui Qi, Jianxun Yuan, Zhiming Wu, Guizhen Chen, Zhihai Wu, Lianao Gao, Ge Yan, Jinghua |
| Author_xml | – sequence: 1 givenname: Rui orcidid: 0000-0001-8469-8730 surname: Shi fullname: Shi, Rui organization: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, University of Chinese Academy of Sciences – sequence: 2 givenname: Chao orcidid: 0000-0002-3953-3782 surname: Shan fullname: Shan, Chao organization: Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences – sequence: 3 givenname: Xiaomin surname: Duan fullname: Duan, Xiaomin organization: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, University of Chinese Academy of Sciences – sequence: 4 givenname: Zhihai orcidid: 0000-0001-6481-4781 surname: Chen fullname: Chen, Zhihai organization: Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University – sequence: 5 givenname: Peipei surname: Liu fullname: Liu, Peipei organization: NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention – sequence: 6 givenname: Jinwen orcidid: 0000-0002-8582-8012 surname: Song fullname: Song, Jinwen organization: Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases – sequence: 7 givenname: Tao surname: Song fullname: Song, Tao organization: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Shanxi Academy of Advanced Research and Innovation, College of Animal Science and Technology, Hebei Normal University of Science and Technology – sequence: 8 givenname: Xiaoshan surname: Bi fullname: Bi, Xiaoshan organization: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Institute of Physical Science and Information, Anhui University – sequence: 9 givenname: Chao surname: Han fullname: Han, Chao organization: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, University of Chinese Academy of Sciences – sequence: 10 givenname: Lianao surname: Wu fullname: Wu, Lianao organization: Institute of Physical Science and Information, Anhui University, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences – sequence: 11 givenname: Ge surname: Gao fullname: Gao, Ge organization: Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences – sequence: 12 givenname: Xue surname: Hu fullname: Hu, Xue organization: Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences – sequence: 13 givenname: Yanan surname: Zhang fullname: Zhang, Yanan organization: Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences – sequence: 14 givenname: Zhou surname: Tong fullname: Tong, Zhou organization: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences – sequence: 15 givenname: Weijin surname: Huang fullname: Huang, Weijin organization: Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control – sequence: 16 givenname: William Jun surname: Liu fullname: Liu, William Jun organization: NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention – sequence: 17 givenname: Guizhen surname: Wu fullname: Wu, Guizhen organization: NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention – sequence: 18 givenname: Bo orcidid: 0000-0002-8895-3679 surname: Zhang fullname: Zhang, Bo organization: Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences – sequence: 19 givenname: Lan surname: Wang fullname: Wang, Lan organization: Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control – sequence: 20 givenname: Jianxun surname: Qi fullname: Qi, Jianxun organization: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Savaid Medical School, University of Chinese Academy of Sciences – sequence: 21 givenname: Hui surname: Feng fullname: Feng, Hui organization: Shanghai Junshi Biosciences Co. Ltd – sequence: 22 givenname: Fu-Sheng orcidid: 0000-0002-8043-6685 surname: Wang fullname: Wang, Fu-Sheng email: fswang302@163.com organization: Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases – sequence: 23 givenname: Qihui orcidid: 0000-0003-3768-0401 surname: Wang fullname: Wang, Qihui email: wangqihui@im.ac.cn organization: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Savaid Medical School, University of Chinese Academy of Sciences – sequence: 24 givenname: George Fu orcidid: 0000-0002-3869-615X surname: Gao fullname: Gao, George Fu email: gaof@im.ac.cn organization: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences – sequence: 25 givenname: Zhiming orcidid: 0000-0002-3234-9616 surname: Yuan fullname: Yuan, Zhiming email: yzm@wh.iov.cn organization: Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences – sequence: 26 givenname: Jinghua orcidid: 0000-0003-0502-3829 surname: Yan fullname: Yan, Jinghua email: yanjh@im.ac.cn organization: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Savaid Medical School, University of Chinese Academy of Sciences |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32454512$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | The Author(s), under exclusive licence to Springer Nature Limited 2020 Copyright Nature Publishing Group Aug 6, 2020 |
| Copyright_xml | – notice: The Author(s), under exclusive licence to Springer Nature Limited 2020 – notice: Copyright Nature Publishing Group Aug 6, 2020 |
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| References | Liu (CR20) 2019; 4 Jiang (CR7) 2020; 395 Du, Zhang, Liu, Jiang (CR27) 2011; 2444 Lan (CR12) 2020; 581 Yuan (CR25) 2020; 368 Hoffmann (CR8) 2020; 181 Lu, Wang, Gao (CR9) 2015; 23 Gao (CR5) 2018; 172 Wang (CR18) 2019; 4 Wang (CR10) 2020; 181 Yan (CR13) 2020; 367 Chen (CR31) 2010; 66 Adams (CR30) 2010; 66 (CR2) 2020; 2 Tan (CR1) 2020; 2 Wang, Wong, Lu, Yan, Gao (CR16) 2016; 133 Corti (CR24) 2016; 351 Zhou (CR6) 2020; 579 Lyon (CR21) 2014; 371 Mulangu (CR22) 2019; 381 Shang (CR11) 2020; 581 Sui (CR26) 2004; 101 Li (CR14) 2015; 25 McCoy (CR28) 2007; 40 Du (CR15) 2009; 7 Wang (CR17) 2016; 8 Gaudinski (CR23) 2019; 393 Wang, Horby, Hayden, Gao (CR3) 2020; 395 Emsley, Lohkamp, Scott, Cowtan (CR29) 2010; 66 (CR4) 2020; 5 Channappanavar (CR19) 2016; 19 M Hoffmann (2381_CR8) 2020; 181 GM Lyon (2381_CR21) 2014; 371 D Corti (2381_CR24) 2016; 351 Q Wang (2381_CR16) 2016; 133 J Shang (2381_CR11) 2020; 581 J Lan (2381_CR12) 2020; 581 Y Li (2381_CR14) 2015; 25 G Lu (2381_CR9) 2015; 23 P Emsley (2381_CR29) 2010; 66 MR Gaudinski (2381_CR23) 2019; 393 VB Chen (2381_CR31) 2010; 66 Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2381_CR4) 2020; 5 P Zhou (2381_CR6) 2020; 579 S Jiang (2381_CR7) 2020; 395 L Liu (2381_CR20) 2019; 4 Q Wang (2381_CR18) 2019; 4 M Yuan (2381_CR25) 2020; 368 L Du (2381_CR27) 2011; 2444 GF Gao (2381_CR5) 2018; 172 L Du (2381_CR15) 2009; 7 S Mulangu (2381_CR22) 2019; 381 C Wang (2381_CR3) 2020; 395 Q Wang (2381_CR10) 2020; 181 AJ McCoy (2381_CR28) 2007; 40 Q Wang (2381_CR17) 2016; 8 R Yan (2381_CR13) 2020; 367 R Channappanavar (2381_CR19) 2016; 19 PD Adams (2381_CR30) 2010; 66 J Sui (2381_CR26) 2004; 101 W Tan (2381_CR1) 2020; 2 The 2019-nCoV Outbreak Joint Field Epidemiology Investigation Team & Li, Q (2381_CR2) 2020; 2 |
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| Title | A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2 |
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