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

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

bioRxiv.org - (2020) vom: 08. Dez. Zur Gesamtaufnahme - year:2020

Sprache:

Englisch

Beteiligte Personen:

Lv, Zhe [VerfasserIn]
Deng, Yong-Qiang [VerfasserIn]
Ye, Qing [VerfasserIn]
Cao, Lei [VerfasserIn]
Sun, Chun-Yun [VerfasserIn]
Fan, Changfa [VerfasserIn]
Huang, Weijin [VerfasserIn]
Sun, Shihui [VerfasserIn]
Sun, Yao [VerfasserIn]
Zhu, Ling [VerfasserIn]
Chen, Qi [VerfasserIn]
Wang, Nan [VerfasserIn]
Nie, Jianhui [VerfasserIn]
Cui, Zhen [VerfasserIn]
Zhu, Dandan [VerfasserIn]
Shaw, Neil [VerfasserIn]
Li, Xiao-Feng [VerfasserIn]
Li, Qianqian [VerfasserIn]
Xie, Liangzhi [VerfasserIn]
Wang, Youchun [VerfasserIn]
Rao, Zihe [VerfasserIn]
Qin, Cheng-Feng [VerfasserIn]
Wang, Xiangxi [VerfasserIn]

Links:

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doi:

10.1101/2020.06.02.129098

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI018072232