Mutations at positions 452 and 486 of the spike glycoprotein receptor binding domain (RBD) in the SARS-CoV-2 XBC.1 variant were analysed from the viewpoint of change in hydrophobicity and amino acid charge. A decrease in hydrophobicity due to mutations at positions 452 and 486 in the spike glycoprotein was observed, which might affect the infectivity of the XBC.1 variant. L452M and F486P improve the hACE2-RBD binding affinity, which might negatively impact the efficacy of vaccines against SARS-CoV-2, primarily based on spike glycoprotein. Notably, the mutation L452M in XBC.1 also indicates its probable zoonotic links.