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Introduction: Prolonged COVID-19 pandemic accelerates the emergence and transmissibility of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants through the accumulation of adaptive mutations. Particularly, adaptive mutations in spike (S) protein of SARS-CoV-2 leads to increased viral infectivity, severe morbidity and mortality, and immune evasion. This study focuses on the phylodynamic distribution of SARS-CoV-2 variants during the year 2021 in India besides analyzing the functional significance of mutations in S-protein of SARS-CoV-2 variants. Methods: Whole genome of SARS-CoV-2 sequences (n = 87957) from the various parts of India over the period of January to December 2021 was retrieved from Global Initiative on Sharing All Influenza Data. All the S-protein sequences were subjected to clade analysis, variant calling, protein stability, immune escape potential, structural divergence, Furin cleavage efficiency, and phylogenetic analysis using various in silico tools. Results: Delta variant belonging to 21A, 21I, and 21J clades was found to be predominant throughout the year 2021 though many variants were also present. A total of 4639 amino acid mutations were found in S-protein. D614G was the most predominant mutation in the S-protein followed by P681R, L452R, T19R, T478K, and D950N. The highest number of mutations was found in the N-terminal domain of S-protein. Mutations in the crucial sites of S-protein impacting pathogenicity, immunogenicity, and fusogenicity were identified. Intralineage diversity analysis showed that certain variants of SARS-CoV-2 possess high diversification. Conclusions: The study has disclosed the distribution of various variants including the Delta, the predominant variant, in India throughout the year 2021. The study has identified mutations in S-protein of each SARS-CoV-2 variant that can significantly impact the virulence, immune evasion, increased transmissibility, high morbidity, and mortality. In addition, it is found that mutations acquired during each viral replication cycle introduce new sub-lineages as studied by intralineage diversity analysis.
RESUMO
INTRODUCTION: The COVID-19 pandemic is associated with high morbidity and mortality, with the emergence of numerous variants. The dynamics of SARS-CoV-2 with respect to clade distribution is uneven, unpredictable and fast changing. METHODS: Retrieving the complete genomes of SARS-CoV-2 from India and subjecting them to analysis on phylogenetic clade diversity, Spike (S) protein mutations and their functional consequences such as immune escape features and impact on infectivity. Whole genome of SARS-CoV-2 isolates (n = 4,326) deposited from India during the period from January 2020 to December 2020 is retrieved from Global Initiative on Sharing All Influenza Data (GISAID) and various analyses performed using in silico tools. RESULTS: Notable clade dynamicity is observed indicating the emergence of diverse SARS-CoV-2 variants across the country. GR clade is predominant over the other clades and the distribution pattern of clades is uneven. D614G is the commonest and predominant mutation found among the S-protein followed by L54F. Mutation score prediction analyses reveal that there are several mutations in S-protein including the RBD and NTD regions that can influence the virulence of virus. Besides, mutations having immune escape features as well as impacting the immunogenicity and virulence through changes in the glycosylation patterns are identified. CONCLUSIONS: The study has revealed emergence of variants with shifting of clade dynamics within a year in India. It is shown uneven distribution of clades across the nation requiring timely deposition of SARS-CoV-2 sequences. Functional evaluation of mutations in S-protein reveals their significance in virulence, immune escape features and disease severity besides impacting therapeutics and prophylaxis.