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TitleStructural basis for the evolution and antibody evasion of SARS-CoV-2 BA.2.86 and JN.1 subvariants.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 7715, Year 2024
Publish dateSep 4, 2024
AuthorsHaonan Yang / Huimin Guo / Aojie Wang / Liwei Cao / Qing Fan / Jie Jiang / Miao Wang / Lin Lin / Xiangyang Ge / Haiyan Wang / Runze Zhang / Ming Liao / Renhong Yan / Bin Ju / Zheng Zhang /
PubMed AbstractThe Omicron subvariants of SARS-CoV-2, especially for BA.2.86 and JN.1, have rapidly spread across multiple countries, posing a significant threat in the ongoing COVID-19 pandemic. Distinguished by ...The Omicron subvariants of SARS-CoV-2, especially for BA.2.86 and JN.1, have rapidly spread across multiple countries, posing a significant threat in the ongoing COVID-19 pandemic. Distinguished by 34 additional mutations on the Spike (S) protein compared to its BA.2 predecessor, the implications of BA.2.86 and its evolved descendant, JN.1 with additional L455S mutation in receptor-binding domains (RBDs), are of paramount concern. In this work, we systematically examine the neutralization susceptibilities of SARS-CoV-2 Omicron subvariants and reveal the enhanced antibody evasion of BA.2.86 and JN.1. We also determine the cryo-EM structures of the trimeric S proteins from BA.2.86 and JN.1 in complex with the host receptor ACE2, respectively. The mutations within the RBDs of BA.2.86 and JN.1 induce a remodeling of the interaction network between the RBD and ACE2. The L455S mutation of JN.1 further induces a notable shift of the RBD-ACE2 interface, suggesting the notably reduced binding affinity of JN.1 than BA.2.86. An analysis of the broadly neutralizing antibodies possessing core neutralizing epitopes reveals the antibody evasion mechanism underlying the evolution of Omicron BA.2.86 subvariant. In general, we construct a landscape of evolution in virus-receptor of the circulating Omicron subvariants.
External linksNat Commun / PubMed:39231977 / PubMed Central
MethodsEM (single particle)
Resolution3.03 - 3.16 Å
Structure data

EMDB-39907, PDB-8zbq:
Local map of Omicron Subvariant JN.1 RBD with ACE2
Method: EM (single particle) / Resolution: 3.03 Å

EMDB-60028: Global map of Omicron Subvariants Spike with ACE2-PD
Method: EM (single particle) / Resolution: 3.16 Å

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / receptor

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