CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; Beijing Life Science Academy, Beijing, China.
CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central Minzu University, Wuhan, China.
Structure. 2024 Aug 8;32(8):1055-1067.e6. doi: 10.1016/j.str.2024.06.012. Epub 2024 Jul 15.
The recently emerged BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 variants have a growth advantage. In this study, we explore the structural bases of receptor binding and immune evasion for the Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants. Our findings reveal that BA.2.86 exhibits strong receptor binding, whereas its JN.1 sub-lineage displays a decreased binding affinity to human ACE2 (hACE2). Through complex structure analyses, we observed that the reversion of R493Q in BA.2.86 receptor binding domain (RBD) plays a facilitating role in receptor binding, while the L455S substitution in JN.1 RBD restores optimal affinity. Furthermore, the structure of monoclonal antibody (mAb) S309 complexed with BA.2.86 RBD highlights the importance of the K356T mutation, which brings a new N-glycosylation motif, altering the binding pattern of mAbs belonging to RBD-5 represented by S309. These findings emphasize the importance of closely monitoring BA.2.86 and its sub-lineages to prevent another wave of SARS-CoV-2 infections.
最近出现的 BA.2.86、JN.1、EG.5、EG.5.1 和 HV.1 变体具有生长优势。在这项研究中，我们探索了奥密克戎 BA.2.86、JN.1、EG.5、EG.5.1 和 HV.1 亚变体的受体结合和免疫逃逸的结构基础。我们的研究结果表明，BA.2.86 表现出强烈的受体结合能力，而其 JN.1 亚谱系对人类 ACE2（hACE2）的结合亲和力降低。通过复杂的结构分析，我们观察到 BA.2.86 受体结合域（RBD）中 R493Q 的回复在受体结合中发挥促进作用，而 JN.1 RBD 中的 L455S 取代恢复了最佳亲和力。此外，与 BA.2.86 RBD 结合的单克隆抗体（mAb）S309 的结构强调了 K356T 突变的重要性，该突变带来了新的 N-糖基化基序，改变了 S309 代表的 RBD-5 类 mAb 的结合模式。这些发现强调了密切监测 BA.2.86 及其亚谱系以防止 SARS-CoV-2 感染再次出现的重要性。
