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.

Omicron (B.1.1.529) - A new heavily mutated variant: Mapped location and probable properties of its mutations with an emphasis on S-glycoprotein.

Omicron, another SARS-CoV-2 variant, has been recorded and reported as a VoC. It has already spread across >30 countries and is a highly mutated variant. We tried to understand the role of mutations in the investigated variants by comparison with previous characterized VoC. We have mapped the mutations in Omicron S-glycoprotein's secondary and tertiary structure landscape using bioinformatics tools and statistical software and developed different models. In addition, we analyzed the effect of diverse mutations in antibody binding regions of the S-glycoprotein on the binding affinity of the investigated antibodies. This study has chosen eight significant mutations in Omicron (D614G, E484A, N501Y, Q493K, K417N, S477N, Y505H G496S), and seven of them are located in the RBD region. We also performed a comparative analysis of the ΔΔG score of these mutations to understand the stabilizing or destabilizing properties of the investigated mutations. The analysis outcome shows that D614G, Q493K, and S477N mutations are stable mutations with ΔΔG scores of 0.351 kcal/mol, 0.470 kcal/mol, and 0.628 kcal/mol, respectively, according to DynaMut estimations. While other mutations (E484A, N501Y, K417N, Y505H, G496S) showed destabilizing results. The D614G, E484A, N501Y, K417N, Y505H, and G496S mutations increased the molecular flexibility of S-glycoprotein to interact with the ACE2 receptor, increasing the variant's infectivity. Our study will contribute to research on the SARS-CoV-2 variant, Omicron, by providing information on the mutational pattern and exciting properties of these eight significant mutations, such as antibody escape and infectivity quotient (stabilizing or destabilizing; increased or decreased molecular flexibility of S-glycoprotein to interact with the human ACE2 receptor).