Immune Escape Potential of SARS-CoV-2 Spike Mutations L452W, F486P, D614G (Q1 2025)

This dataset contains a comprehensive mutation profile analysis of the SARS-CoV-2 Spike protein from sequences collected during Q1 of 2025 . Using alignment-based mutation calling via Nextclade and functional annotation using Biopython tools locally, I identified the most frequent Spike mutation patters such as L452W, F486P, D614G. These mutations were observed across multiple lineages including JN.1, KP.2, LB.1 Each of these mutations has been previously associated with immune escape properties, enhanced ACE2 binding, and reduced neutralization by monoclonal antibodies and vaccine-induced immunity. Functional Mutation Analysis L452W is located within receptor Binding Domain (RBD), position 452. It enhances ACE2 affinity and reduces neutralization by therapeutic antibodies such as Bamlanivimab and C135. As described by Zhou et al., Nature 2022 that L452R/W mutations are linked to immune evasion and increased transmissibility this study confirms this pattern. F486P located within RBD, position 486 disrupts antibody binding at a conserved epitope; may impact neutralization by class 1 and class 2 antibodies. The F486 substitutions reduce binding by potent neutralizing antibodies targeting the ACE2 interface as described by McCallum et al., Science 2022. D614G is located within Spike S1 domain it stabilizes Spike trimer, enhances fusion efficiency, and increases viral infectivity. D614G increases SARS-CoV-2 spike flexibility (Gobeil et al., PNAS 2021) and ACE2 receptor engagement is also enhanced. Together, this mutation profile suggests a potential escape mechanism from both vaccine-induced immunity and therapeutic monoclonal antibodies, while maintaining high ACE2 binding affinity and transmission fitness. Methods Overview Sequences obtained from NCBI/GISAID EpiCoV databases Mutation profiles extracted using Nextclade and iVar. Lineage classification via Pangolin Mutation annotations mapped to Wuhan-Hu-1 reference genome Immune escape prediction based on known antibody epitopes from CoV-AbDab and structural studies All methods are fully reproducible and generated fasta file is included with this dataset. References 1. Zhou, D., et al. (2022). Evidence of escape of SARS-CoV-2 variant BQ.1.1 from vaccine and therapeutic antibody protection. Nature. - https://doi.org/10.1038/s41586-022-04967-2 2. McCallum, M., et al. (2022). Structural basis of potent antibody responses to SARS-CoV-2 variants . Science. - https://doi.org/10.1126/science.abq2652 3. Gobeil, S.M.C., et al. (2021). Effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2. PNAS. - https://doi.org/10.1073/pnas.2106524118 4. Wang, Q., et al. (2023). Antibody resistance of XBB.1.5 and related variants. Cell Reports. - https://doi.org/10.1016/j.celrep.2023.112322 5. WHO. Tracking SARS-CoV-2 variants: Omicron sublineages and recombinants. - https://www.who.int/publications/m/item/tracking-sars-cov-2-variants