1. Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist circulating variants.
- Author
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Li, Tingting, Xue, Wenhui, Zheng, Qingbing, Song, Shuo, Yang, Chuanlai, Xiong, Hualong, Zhang, Sibo, Hong, Minqing, Zhang, Yali, Yu, Hai, Zhang, Yuyun, Sun, Hui, Huang, Yang, Deng, Tingting, Chi, Xin, Li, Jinjin, Wang, Shaojuan, Zhou, Lizhi, Chen, Tingting, Wang, Yingbin, Cheng, Tong, Zhang, Tianying, Yuan, Quan, Zhao, Qinjian, Zhang, Jun, McLellan, Jason S, Zhou, Z Hong, Zhang, Zheng, Li, Shaowei, Gu, Ying, and Xia, Ningshao
- Subjects
CHO Cells ,Vero Cells ,Animals ,Humans ,Cricetulus ,Mice ,Receptors ,Virus ,Antibodies ,Monoclonal ,Antibodies ,Viral ,Epitopes ,Neutralization Tests ,Immunization ,Passive ,Binding Sites ,Protein Multimerization ,HEK293 Cells ,Pandemics ,Sf9 Cells ,Spike Glycoprotein ,Coronavirus ,Middle East Respiratory Syndrome Coronavirus ,Broadly Neutralizing Antibodies ,Chlorocebus aethiops ,COVID-19 ,SARS-CoV-2 ,Prevention ,Vaccine Related ,Emerging Infectious Diseases ,Pneumonia & Influenza ,Biotechnology ,Pneumonia ,Infectious Diseases ,Lung ,Immunization ,Biodefense ,Infection - Abstract
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.
- Published
- 2021