Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain

作者：Wang, Yanqun^*; Zhang, Zhaoyong; Yang, Minnan; Xiong, Xinyi; Yan, Qihong; Cao, Lei; Wei, Peilan; Zhang, Yuting; Zhang, Lu; Lv, Kexin; Chen, Jiantao; Liu, Xuesong; Zhao, Xiaochu; Xiao, Juxue; Zhang, Shengnan; Zhu, Airu; Gan, Mian; Zhang, Jingjun; Cai, Ruoxi; Zhuo, Jianfen; Zhang, Yanjun; Rao, Haiyue; Qu, Bin; Zhang, Yuanyuan; Chen, Lei; Dai, Jun; Cheng, Linling; Hu, Qingtao; Chen, Yaoqing; Lv, Huibin; So, Ray T. Y.; Peiris, Malik; Zhao, Jingxian; Liu, Xiaoqing^*

来源：Cell Reports, 2024, 43(1): 113653.

DOI：10.1016/j.celrep.2023.113653

• SARS-COV-2
• PREDICTION
• MUTATIONS

Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor -binding -domain -targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryoEM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor -binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre -emergent SARS-CoV-2 VOCs.

• 单位
  中山大学; 1; 广州医学院; 中国科学院