Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
Abstract The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in 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 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.One sentence summary A potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
bioRxiv.org - (2020) vom: 08. Dez. Zur Gesamtaufnahme - year:2020 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Lv, Zhe [VerfasserIn] |
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Links: |
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doi: |
10.1101/2020.06.02.129098 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI018072232 |
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520 | |a Abstract The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in 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 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.One sentence summary A potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor. | ||
700 | 1 | |a Deng, Yong-Qiang |e verfasserin |4 aut | |
700 | 1 | |a Ye, Qing |e verfasserin |4 aut | |
700 | 1 | |a Cao, Lei |e verfasserin |4 aut | |
700 | 1 | |a Sun, Chun-Yun |e verfasserin |4 aut | |
700 | 1 | |a Fan, Changfa |e verfasserin |4 aut | |
700 | 1 | |a Huang, Weijin |e verfasserin |4 aut | |
700 | 1 | |a Sun, Shihui |e verfasserin |4 aut | |
700 | 1 | |a Sun, Yao |e verfasserin |4 aut | |
700 | 1 | |a Zhu, Ling |e verfasserin |4 aut | |
700 | 1 | |a Chen, Qi |e verfasserin |4 aut | |
700 | 1 | |a Wang, Nan |e verfasserin |4 aut | |
700 | 1 | |a Nie, Jianhui |e verfasserin |4 aut | |
700 | 1 | |a Cui, Zhen |e verfasserin |4 aut | |
700 | 1 | |a Zhu, Dandan |e verfasserin |4 aut | |
700 | 1 | |a Shaw, Neil |e verfasserin |4 aut | |
700 | 1 | |a Li, Xiao-Feng |e verfasserin |4 aut | |
700 | 1 | |a Li, Qianqian |e verfasserin |4 aut | |
700 | 1 | |a Xie, Liangzhi |e verfasserin |4 aut | |
700 | 1 | |a Wang, Youchun |e verfasserin |4 aut | |
700 | 1 | |a Rao, Zihe |e verfasserin |4 aut | |
700 | 1 | |a Qin, Cheng-Feng |e verfasserin |4 aut | |
700 | 1 | |a Wang, Xiangxi |e verfasserin |4 aut | |
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