Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

The Omicron variant has been detected in nearly 150 countries. We analyzed the mutational landscape of Omicron throughout the genome, focusing the S-glycoprotein. We also evaluated mutations in the antibody-binding regions and observed some important mutations overlapping those of previous variants including N501Y, D614G, H655Y, N679K, and P681H. Various new receptor-binding domain mutations were detected, including Q493K, G496S, Q498R, S477N, G466S, N440K, and Y505H. New mutations were found in the NTD (Δ143-145, A67V, T95I, L212I, and Δ211) including one new mutation in fusion peptide (D796Y). There are several mutations in the antibody-binding region including K417N, E484A, Q493K, Q498R, N501Y, and Y505H and several near the antibody-binding region (S477N, T478K, G496S, G446S, and N440K). The impact of mutations in regions important for the affinity between spike proteins and neutralizing antibodies was evaluated. Furthermore, we examined the effect of significant antibody-binding mutations (K417N, T478K, E484A, and N501Y) on antibody affinity, stability to ACE2 interaction, and possibility of amino acid substitution. All the four mutations destabilize the antibody-binding affinity. This study reveals future directions for developing neutralizing antibodies against the Omicron variant. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00532-4.