| Literature DB >> 33431876 |
Chao Zhang1, Yifan Wang2, Yuanfei Zhu3, Caixuan Liu2, Chenjian Gu3, Shiqi Xu1, Yalei Wang1, Yu Zhou1, Yanxing Wang2,4, Wenyu Han2, Xiaoyu Hong2, Yong Yang1, Xueyang Zhang1, Tingfeng Wang1, Cong Xu2, Qin Hong2, Shutian Wang2, Qiaoyu Zhao2, Weihua Qiao1, Jinkai Zang1, Liangliang Kong5, Fangfang Wang5, Haikun Wang1, Di Qu3,6, Dimitri Lavillette1, Hong Tang1, Qiang Deng7, Youhua Xie8, Yao Cong9,10, Zhong Huang11.
Abstract
The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.Entities:
Year: 2021 PMID： 33431876 DOI： 10.1038/s41467-020-20465-w
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919