A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD

作者：Wang, Xiaofei; Hu, Ao; Chen, Xiangyu; Zhang, Yixin; Yu, Fei; Yue, Shuai; Li, Arong; Zhang, Junsong; Pan, Zhiwei; Yang, Yang; Lin, Yao; Gao, Leiqiong; Zhou, Jing; Zhao, Jing; Li, Fang; Shi, Yaling; Huang, Feng; Yang, Xiaofan; Peng, Yi; Tu, Luoyang; Zhang, Huan; Zheng, Huanying; He, Jun; Zhang, Hui; Xu, Lifan; Huang, Qizhao; Zhu, Yongqun^*; Deng, Kai^*; Ye, Lilin^*

来源：Signal Transduction and Targeted Therapy, 2022, 7(1): 114.

DOI：10.1038/s41392-022-00954-8

• CRYO-EM STRUCTURE
• SPIKE
• COCKTAIL
• COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

• 单位
  中国科学院; 中山大学; 浙江大学; 广州医学院; 南方医科大学; 广东省人民医院