[Source: Science, full page: (LINK). Abstract, edited.]
Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
Zhe Lv1,8,*, Yong-Qiang Deng2,*, Qing Ye2,*, Lei Cao1,*, Chun-Yun Sun3,*, Changfa Fan4,*, Weijin Huang5, Shihui Sun2, Yao Sun1, Ling Zhu1, Qi Chen2, Nan Wang1,8, Jianhui Nie5, Zhen Cui1,8, Dandan Zhu1, Neil Shaw1, Xiao-Feng Li2, Qianqian Li5, Liangzhi Xie3,6,7,†, Youchun Wang5,†, Zihe Rao1,†, Cheng-Feng Qin2,†, Xiangxi Wang1,8,†
1 CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. 2 State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China. 3 Beijing Protein and Antibody R&D Engineering Center, Sinocelltech Ltd., Beijing 100176, China. 4 Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China. 5 Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China. 6 Beijing Antibody Research Key Laboratory, Sino Biological Inc., Building 9, Jing Dong Bei Technology Park, No.18 Ke Chuang 10th St, BDA, Beijing, 100176, China. 7 Cell Culture Engineering Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China. 8 University of Chinese Academy of Sciences, Beijing 100049, China.
†Corresponding author. Email: xiangxi@ibp.ac.cn (X.W.); qincf@bmi.ac.cn (C.-F.Q.); wangyc@nifdc.org.cn (Y.W.); liangzhi@yahoo.com (L.X.); raozh@tsinghua.edu.cn (Z.R.)
* These authors contributed equally to this work.
Science 23 Jul 2020: eabc5881 | DOI: 10.1126/science.abc5881
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.
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Keywords: SARS-CoV-2; COVID-19; SARS-CoV; Monoclonal antibodies.
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