Researchers identify structural characteristics of newly emerged SARS-CoV-2 variants

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to adapt to the herd immunity background and evolves into numerous sub-variants. Prof. George Fu Gao's lab at Institute of Microbiology  of Chinese Academy of Sciences (IMCAS) revealed the spike (S) protein structures of the recently emerged BA.2.86, JN.1, EG.5, EG.5.1 and HV.1 variants of SARS-CoV-2, and conducted systematic comparative analysis on these sub-variants. This work was published in Structure.

The variants evolved from BA.2 mainly separated into two branches. The branch represented by BA.2.86 and JN.1 is more likely to show the "3-receptor-binding domains (RBDs)-up" state of the S protein under the induction of its receptor, human angiotensin converting enzyme 2 (hACE2), and the branch represented by XBB, EG.5, HV.1 is more likely to show the "2-RBDs-up, 1-RBD-down" state under the induction of hACE2.

Compared to other variants, the branch represented by BA.2.86 carries a new N-glycosylation at residue 354 due to the K356T mutation, and this glycosylation site affects the binding to antibodies, such as S309. Compared with the BA.2 strain circulating in 2022, the RBD surface of the BA.2.86 and JN.1 showed significant electrostatic changes, which enhanced their immune escape. Among them, BA.2.86 has a higher receptor binding affinity than its progeny, JN.1. While JN.1 escapes from more antibodies. Structural analysis showed that the R493Q reverting mutation in the BA.2.86 RBD promoted receptor binding, whereas the L455S mutation in the JN.1 RBD reduced the receptor-binding affinity.

This study further supports the previous conclusion of Prof. GAO's lab: During the evolution of SARS-CoV-2 variants, immune escape is gradually enhanced, while receptor binding capacity fluctuates and remains in a moderate range (2 digital nanomoles).