The lists of the AA mutations present in SARS-CoV-2 variants detected using the sequence of the Wuhan genome (GISAID accession ID: EPI_ISL_402124) as reference were retrieved from the Global Initiative for Sharing All Influenza Data (GISAID) database (https://www.gisaid.org/) at different time points.
The AA substitutions were classified according to two criteria:
Differences in hydrophobicity (ΔHydrophobicity) between the mutated and the original residue was calculated based on the consensus hydrophobic scale developed by Eisenberg.