ArticleVirus evolution2024
Deep mutational scanning of SARS-CoV-2 Omicron BA.2.86 and epistatic emergence of the KP.3 variant.
Article in Virus evolution, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Deep mutational scanning reveals the antibody escape and infectivity landscape of SARS-CoV-2 Omicron JN.1 and XEC receptor-binding domains.Emerging microbes & infections · 2026Article
- A dimeric mRNA vaccine based on key-mutant and KP.3 RBDs induces broad-spectrum immunity and protects mice against JN.1 and XDV challenges.Molecular biomedicine · 2026Article
- Localized Rigidification and Allosteric Modulation Mechanisms of SARS-CoV-2 Spike Neutralization by Class 3 and Class 4 Antibodies at Atomic Resolution: An Integrated Computational Study of Binding, Dynamics, and Allostery.bioRxiv : the preprint server for biology · 2026Article
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- A deep mutational scanning-informed protein language model predicts SARS-CoV-2 evolution dynamics with spatiotemporal resolution.Nature microbiology · 2026Article
- Deep mutational scanning of recent SARS-CoV-2 variants highlights changing amino acid preferences within epistatic hotspot residues.PLoS pathogens · 2026Article
- Epistasis and background dependence in the evolution of Omicron variants of the SARS-CoV-2 spike protein.Molecular biology and evolution · 2026Article
- Mechanisms of Binding and Immune Escape Resistance for Broadly Neutralizing Antibodies Targeting Distinct Conserved SARS-CoV-2 Spike Epitopes: A Hierarchical Approach Integrating Mutational Profiling and Energy Landscape Analysis.International journal of molecular sciences · 2026Article
- Article
- Frustration Landscapes of Broadly Neutralizing SARS-CoV-2 Spike Antibodies Targeting Conserved Epitopes Reveal Energetic Logic of Escape-Proof and Escape-Prone Mechanisms.bioRxiv : the preprint server for biology · 2026Article
- Systematic profiling of SARS-CoV-2 structural protein-specific T cell epitopes in Omicron infections following inactivated vaccination.iScience · 2026Article
- Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures.bioRxiv : the preprint server for biology · 2026Article
- Origins and breadth of pairwise epistasis in an α-helix of β-lactamase TEM-1.Nature communications · 2026Article
- SARS-CoV-2 variants: biology, pathogenicity, immunity and control.Nature reviews. Microbiology · 2026Review
- Characterization of the heterogeneity in SARS-CoV-2 fitness dynamics via graph representation learning.PLoS computational biology · 2026Article
- Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures.Virus evolution · 2026Article
- 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
- Neutral Frustration Landscape Architecture of SARS-CoV-2 Spike-Antibody Interfaces Shapes Immune Evasion Mechanisms for Ultrapotent Neutralizing Antibodies and Determines Pathways of Viral Adaptation: Insights from Integrative Computational Approach.bioRxiv : the preprint server for biology · 2025Article
- Modeling the Mutational Effects on Biochemical Phenotypes of SARS-CoV-2 Using Molecular Fields.Biomolecules · 2025Article
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Abstract
Deep mutational scanning experiments aid in the surveillance and forecasting of viral evolution by providing prospective measurements of mutational effects on viral traits, but epistatic shifts in the impacts of mutations can hinder viral forecasting when measurements were made in outdated strain backgrounds. Here, we report measurements of the impact of all single amino acid mutations on ACE2-binding affinity and protein folding and expression in the SARS-CoV-2 Omicron BA.2.86 spike receptor-binding domain. As with other SARS-CoV-2 variants, we find a plastic and evolvable basis for receptor binding, with many mutations at the ACE2 interface maintaining or even improving ACE2-binding affinity. Despite its large genetic divergence, mutational effects in BA.2.86 have not diverged greatly from those measured in its Omicron BA.2 ancestor. However, we do identify strong positive epistasis among subsequent mutations that have accrued in BA.2.86 descendants. Specifically, the Q493E mutation that decreased ACE2-binding affinity in all previous SARS-CoV-2 backgrounds is reversed in sign to enhance human ACE2-binding affinity when coupled with L455S and F456L in the currently emerging KP.3 variant. Our results point to a modest degree of epistatic drift in mutational effects during recent SARS-CoV-2 evolution but highlight how these small epistatic shifts can have important consequences for the emergence of new SARS-CoV-2 variants.
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