Mutational and evolutionary dynamics of non-structural and spike proteins from variants of concern (VOC) of SARS-CoV-2 in India.

Monitoring the genetic diversity and emerging mutations in SARS-CoV-2 remains crucial for understanding its evolution, given the virus's persistence in India. This study analyzes lineage dynamics, mutation screening, structural analysis, and phylodynamics of SARS-CoV-2 variants of concern (VOC) in India from October 2020 to September 2023. The predominant variants identified were alpha, beta, delta, and omicron, with delta and omicron making up 76.05 % of sequenced genomes. The B.1.617.2 lineage of the delta variant was the major contributor to COVID-19 cases before the rise of omicron. Mutation screening of non-structural proteins (NSPs) and spike proteins revealed distinct profiles for each VOC. Co-mutation patterns were analyzed, showing structural and energetic alterations. Phylogenetic analysis indicated that nsp1, nsp3, nsp4, nsp13, and nsp14 were strongly associated with increased mutation load. The study also highlighted that nsp14 and spike have similar mutability patterns, underscoring nsp14's critical role in SARS-CoV-2 infectivity and persistence. This research provides a comprehensive view of SARS-CoV-2's evolution and persistence in India.