ArticlePLoS pathogens2023
Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 synergistically enhances antibody evasion and ACE2 binding.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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81 citing papers in PubMed.
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- A predictive model for rapid assessment of protective efficacy against emerging SARS-CoV-2 variants.Infectious Disease Modelling · 2026Article
- A deep mutational scanning-informed protein language model predicts SARS-CoV-2 evolution dynamics with spatiotemporal resolution.Nature microbiology · 2026Article
- Broad Neutralizing Antibodies Against SARS-CoV-2: Current Progress and Engineering Strategies.Viruses · 2026Review
- Deep mutational scanning of recent SARS-CoV-2 variants highlights changing amino acid preferences within epistatic hotspot residues.PLoS pathogens · 2026Article
- Trends in funding for coronavirus vaccine research and development: implications for preparedness against future coronavirus threats.NPJ vaccines · 2026Review
- Stringent selection drives convergence toward omicron-like SARS-CoV-2 receptor-binding motifs.Nature communications · 2026Article
- Repeated COVID-19 vaccine boosters elicit variant-specific memory B cells in humans.Cell reports · 2026Article
- Antibody escape drives emergence of diverse spike haplotypes resembling variants of concern in persistent SARS-CoV-2 infections.Cell reports. Medicine · 2026Article
- SARS-CoV-2 variants: biology, pathogenicity, immunity and control.Nature reviews. Microbiology · 2026Review
- Comprehensive whole-genome characterization of SARS-CoV-2 strains in Jining China 2024-2025.Frontiers in microbiology · 2026Article
- Optimizing the breadth of SARS-CoV-2-neutralizing antibodies in vivo and in silico.Human vaccines & immunotherapeutics · 2025Review
- Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.Journal of virology · 2025Article
- A highly divergent cryptic SARS-CoV-2 lineage exhibits strong receptor binding and immune evasion.medRxiv : the preprint server for health sciences · 2025Article
- Constrained Evolutionary Funnels Shape Viral Immune Escape.bioRxiv : the preprint server for biology · 2025Article
- Repeated COVID-19 vaccine boosters elicit variant-specific memory B cells in humans.bioRxiv : the preprint server for biology · 2025Article
- What Has SARS-CoV-2 Taught Us About Evolution?Cureus · 2025Review
- Inference of Cytochrome P450 Evolutionary History Using Structural and Physicochemical Metrics.Genome biology and evolution · 2025Article
- Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.bioRxiv : the preprint server for biology · 2025Article
21 more citing papers are in PubMed but not listed here.
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25 authors.
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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.
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