Science, 23 July, 2020, DOI：https://doi.org/10.1126/science.abc5881

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

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*

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.

Article link：http://dx.doi.org/10.1126/science.abc5881