State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, 361102, Xiamen, Fujian, China.
National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, 361102, Xiamen, Fujian, China.
Nat Commun. 2021 Sep 27;12(1):5652. doi: 10.1038/s41467-021-25997-3.
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.
众多 SARS-CoV-2 变体的出现给全球控制 COVID-19 大流行的努力带来了新的挑战。在这里，我们获得了两种针对沙贝科病毒受体结合域（RBD）的具有亚皮摩尔亲和力的交叉中和抗体（7D6 和 6D6），并能有效中和真实的 SARS-CoV-2。晶体结构表明，这两种抗体结合的是一个不同于现有抗体识别的隐匿位点，并且在沙贝科病毒分离株中高度保守。这两种抗体与 RBD 的结合与相邻的 N 端结构域发生冲突，破坏了病毒刺突。这两种抗体都能很好地抵抗目前流行的 SARS-CoV-2 变体中的突变。因此，我们的结果与公共卫生直接相关，为被动抗体治疗剂甚至主动预防性治疗剂提供了选择。它们还可以为泛沙贝科病毒疫苗的设计提供信息。
