Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, t...

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Veröffentlicht in:Science (American Association for the Advancement of Science) Jg. 369; H. 6510; S. 1505
Hauptverfasser: Lv, Zhe, Deng, Yong-Qiang, Ye, Qing, Cao, Lei, Sun, Chun-Yun, Fan, Changfa, Huang, Weijin, Sun, Shihui, Sun, Yao, Zhu, Ling, Chen, Qi, Wang, Nan, Nie, Jianhui, Cui, Zhen, Zhu, Dandan, Shaw, Neil, Li, Xiao-Feng, Li, Qianqian, Xie, Liangzhi, Wang, Youchun, Rao, Zihe, Qin, Cheng-Feng, Wang, Xiangxi
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 18.09.2020
Schlagworte:
Angiotensin-Converting Enzyme 2
Animals
Antibodies, Monoclonal, Humanized - chemistry
Antibodies, Monoclonal, Humanized - therapeutic use
Antibodies, Neutralizing - chemistry
Antibodies, Neutralizing - therapeutic use
Betacoronavirus - immunology
Chlorocebus aethiops
Coronavirus Infections - therapy
COVID-19
Epitope Mapping
Humans
Immunoglobulin Fab Fragments - chemistry
Lung - immunology
Mice
Pandemics
Peptidyl-Dipeptidase A - immunology
Pneumonia, Viral - therapy
Protein Domains
Protein Multimerization
Receptors, Virus - immunology
SARS Virus - immunology
SARS-CoV-2
Vero Cells
ISSN:1095-9203, 1095-9203
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Zusammenfassung:The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.abc5881