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 of SARS-CoV-2 still remains to be crucial in India. This study extensively analyzes the lineage dynamics, mutation screening, structural analysis, and phylodynamics of SARS-CoV-2 variants of concern (VOC) in India from October 2020 to September 2023. Predominant variants identified include alpha, beta, delta, and omicron, with delta and omicron making up 76.05% of sequenced genomes. The B.1.617.2 lineage of delta was the major contributor to COVID-19 cases before the rapid rise of omicron. Mutation screening of non-structural proteins (NSPs) and spike revealed distinct profiles for each VOC. Co-mutation patterns/networks of the most frequently observed mutations specific for each VOC were also identified and subsequently structural and energetic alteration of the co-mutants were analyzed using rigorous molecular dynamics simulations. Furthermore, comparative analysis of phylogenetic trees based on genomic and mutational data revealed that nsp1, nsp3, nsp4, nsp13, and nsp14 exhibit strongest association with the increased mutation load across the genome of SARS-CoV-2 in Indian population. Our comparative phylogenetic study also revealed that mutability patterns of nsp14 and spike have highest similarity supporting critical role of nsp14 for SARS-CoV-2 infectivity and persistence. This research provides a comprehensive overview of SARS-CoV-2 evolution in India.