Coronavirus disease 2019 (COVID-19),(COVID-19), caused by SARS-CoV-2, has had a disastrous effect worldwide during the previous two years due to widespread infections with SARS-CoV-2 and its emerging variations.
More than 650 million confirmed cases and over 6.6 million deaths have been attributed to successive waves of SARS-CoV-2 infections as of 07th December 2022. Similar to other RNA viruses, SARS-CoV-2 is more susceptible to genetic evolution and spontaneous mutations over time, resulting in the continual emergence of variants with distinct characteristics. Spontaneous mutations of SARS-CoV-2 variants increase its transmissibility, virulence, and disease severity and diminish the efficacy of therapeutics and vaccines, resulting in vaccine-breakthrough infections and re-infection, leading to high mortality and morbidity rates. In this study, we evaluated 10,531 full genome sequences of all reported variants globally through a computational approach to assess the spread and emergence of the mutations in the SARS-CoV-2 genome. The publically available data sources of NextCladeCLI 2.3.0 (https://clades.nextstrain.org/) and NextStrain (https://nextstrain.org/) were searched for tracking SARS-CoV-2 mutations, analyzed using the PROVEAN, Polyphen, and Predict SNP mutational analysis tools and validated by Machine Learning models. Compared to the Wuhan-Hu-1 reference strain NC 045512.2, genome-wide annotations showed 16,954 mutations in the SARSCoV-2 genome. We determined that the Omicron variation had 6,307 mutations (retrieved sequence:1947), including 67.8% unique mutations, more than any other variant evaluated in this study. The spike protein of the Omicron variant harbored 876 mutations, including 512 unique and 443 deleterious mutations. Among these deleterious mutations, 187 were common and 256 In review were unique non-synonymous mutations. In contrast, after analyzing 1,884 sequences of the Delta variant, we discovered 4,468 mutations, of which 66% were unique, and not previously reported in other variants. Mutations affecting spike proteins are mostly found in RBD regions for omicron whereas most of the delta variant mutations drawn focus on amino acid regions ranging from 911 to 924 in the context of B cell epitope prediction, T cell epitope prediction, and mutational stability impact analysis protruding that omicron is more transmissible. The pathogenesis of the Omicron variant could be prevented if the deleterious and persistent unique immunosuppressive mutations can be targeted for vaccination or small-molecule inhibitor designing. Thus, our findings will help researchers to monitor and track the continuously evolving nature of SARS-CoV-2 strains, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategies.