Characterization of private mutations in the spike protein of SARS-CoV-2 correlates with viral prevalence.

BACKGROUND

SARS-CoV-2 has continued to spread globally since its outbreak. As the virus evolves, new variants affect the efficacy of current vaccines and treatments. Therefore, understanding and explaining the viral prevalence of SARS-CoV-2 is crucial for developing effective public health strategies.

METHODS

Genomic information from the SARS-CoV-2 network surveillance laboratories in Jiangsu Province in 2023 was collected. The impact of private mutations on binding affinity of the spike protein to Angiotensin Converting Enzyme 2 (ACE2) was evaluated by Bioinformatic analyses, pseudovirus infection assays and Bio-Layer Interferometry (BLI). The impact of private mutations on antibody escape capacity was evaluated through Pseudotyped Virus Neutralization Assay (PVNA).

RESULTS

The major circulating SARS-CoV-2 sublineages in Jiangsu Province in 2023 included BA.5.2*, XBB.1.5*, XBB.1.16*, XBB.1.22*, and XBB.1.9*. Key private mutations analyzed were E748V in XBB.1.5.24, H146K and I210T in XBB.1.22.1, H146K + I210T, and L455F in EG.5.1/EG.5.1.1. Bioinformatic analyses, pseudovirus infection assays, and BLI results showed that L455F significantly increased the spike protein's binding affinity to ACE2. PVNA results indicated that H146K and I210T enhance the antibody evasion ability of the XBB.1.22.1 spike protein, while L455F did so for EG.5.1/EG.5.1.1. However, E748V increased antibody neutralization sensitivity for XBB.1.5.24. E748V, I210T, and L455F became characteristic of their respective descent lineages GF.1, FY.3.1, and HK.3. The epidemic durations of FY.3.1 and HK.3 were longer than that of GF.1.

CONCLUSIONS

Continuous monitoring and functional analysis of SARS-CoV-2 private mutations can be an effective approach for explaining patterns of viral prevalence. This has significant implications for the timely formulation of prevention and control measures.