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

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

Posted 02 Jun 2020
bioRxiv DOI: 10.1101/2020.06.02.129098 (published DOI: 10.1126/science.abc5881)

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. ### Competing Interest Statement The authors have declared no competing interest.

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