Journal Article

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist circulating variants

Wang, Yingbin, Deng, Tingting, Yuan, Quan, Zheng, Qingbing, Gu, Ying, Li, Jinjin, Zhang, Tianying, Zhang, Sibo, Li, Tingting, Cheng, Tong, Zhang, Zheng, Huang, Yang, Sun, Hui, Chi, Xin, Wang, Shaojuan, Zhao, Qinjian, Yang, Chuanlai, Hong, Minqing, Song, Shuo, Xia, Ningshao, Xiong, Hualong, Chen, Tingting, Yu, Hai, Zhang, Yuyun, Li, Shaowei, Zhang, Yali, Zhou, Lizhi, Zhou, Z. Hong, Xue, Wenhui, McLellan, Jason S., Zhang, Jun

2021

Overview

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines. Antibodies (Abs) targeting highly conserved epitopes are important tools against emerging virus variants. Here, the authors characterize Abs that recognize a cryptic epitope in the receptor-binding domain of SARS-CoV-2 spike that is well conserved and show that these Abs can neutralize several variants of concerns.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
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