A comprehensive analysis of the mutational landscape of the newly emerging Omicron (B.1.1.529) variant and comparison of mutations with VOCs and VOIs.

The Omicron variant is spreading rapidly throughout several countries. Thus, we comprehensively analyzed Omicron's mutational landscape and compared mutations with VOC/VOI. We analyzed SNVs throughout the genome, and AA variants (NSP and SP) in VOC/VOI, including Omicron. We generated heat maps to illustrate the AA variants with high mutation prevalence (> 75% frequency) of Omicron, which demonstrated eight mutations with > 90% prevalence in ORF1a and 29 mutations with > 75% prevalence in S-glycoprotein. A scatter plot for Omicron and VOC/VOI's cluster evaluation was computed. We performed a risk analysis of the antibody-binding risk among four mutations (L452, F490, P681, D614) and observed three mutations (L452R, F490S, D614G) destabilized antibody interactions. Our comparative study evaluated the properties of 28 emerging mutations of the S-glycoprotein of Omicron, and the ΔΔG values. Our results showed K417N with minimum and Q954H with maximum ΔΔG value. Furthermore, six important RBD mutations (G339D, S371L, N440K, G446S, T478K, Q498R) were chosen for comprehensive analysis for stabilizing/destabilizing properties and molecular flexibility. The G339D, S371L, N440K, and T478K were noted as stable mutations with 0.019 kcal/mol, 0.127 kcal/mol, 0.064 kcal/mol, and 1.009 kcal/mol. While, G446S and Q498R mutations showed destabilizing results. Simultaneously, among six RBD mutations, G339D, G446S, and Q498R mutations increased the molecular flexibility of S-glycoprotein. This study depicts the comparative mutational pattern of Omicron and other VOC/VOI, which will help researchers to design and deploy novel vaccines and therapeutic antibodies to fight against VOC/VOI, including Omicron.