Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants with substantial growth advantages, such as EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. L455F and F456L evade RBD-targeting Class 1 public NAbs, reducing the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. The perturbed receptor-binding mode leads to the exceptional ACE2 binding and NAb evasion, as revealed by structural analyses. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.
Funder
Ministry of Science and Technology of the People's Republic of China
Changping Laboratory
Excellent Young Scientists Fund
Publisher
Public Library of Science (PLoS)
Subject
Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology
Reference45 articles.
1. The evolution of SARS-CoV-2.;PV Markov;Nature Reviews Microbiology.,2023
2. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection;Y Cao;Nature,2022
3. Further humoral immunity evasion of emerging SARS-CoV-2 BA.4 and BA.5 subvariants;F Jian;The Lancet Infectious Diseases,2022
4. Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75;Y Cao;Cell Host Microbe,2022
5. Antiviral and bivalent vaccine efficacy against an omicron XBB.1.5 isolate;R Uraki;The Lancet Infectious Diseases,2023
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献