Divergent mutations of Delta and Omicron variants: key players behind differential viral attributes across the COVID-19 waves.

The third SARS-CoV-2 pandemic wave causing Omicron variant has comparatively higher replication rate and transmissibility than the second wave-causing Delta variant. The exact mechanism behind the differential properties of Delta and Omicron in respect to infectivity and virulence is not properly understood yet. This study reports the analysis of different mutations within the receptor binding domain (RBD) of spike glycoprotein and non-structural protein (nsp) of Delta and Omicron strains. We have used computational studies to evaluate the properties of Delta and Omicron variants in this work. Q498R, Q493R and S375F mutations of RBD showed better docking scores for Omicron compared to Delta variant of SARS-CoV-2, whereas nsp3_L1266I with PARP15 (7OUX), nsp3_L1266I with PARP15 (7OUX), and nsp6_G107 with ISG15 (1Z2M) showed significantly higher docking score. The findings of the present study might be helpful to reveal the probable cause of relatively milder form of COVID-19 disease manifested by Omicron in comparison to Delta variant of SARS-CoV-2 virus. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-023-00823-0.

Emergence of a unique SARS-CoV-2 Delta sub-cluster harboring a constellation of co-appearing non-Spike mutations.

Accumulation of diverse mutations across the structural and nonstructural genes is leading to rapid evolution of SARS-CoV-2, altering its pathogenicity. We performed whole genome sequencing of 239 SARS-CoV-2 RNA samples collected from both adult and pediatric patients across eastern India (West Bengal), during the second pandemic wave in India (April-May 2021). In addition to several common spike mutations within the Delta variant, a unique constellation of eight co-appearing non-Spike mutations was identified, which revealed a high degree of positive mutual correlation. Our results also demonstrated the dynamics of SARS-CoV-2 variants among unvaccinated pediatric patients. 41.4% of our studied Delta strains harbored this signature set of eight co-appearing non-Spike mutations and phylogenetically out-clustered other Delta sub-lineages like 21J, 21A, or 21I. This is the first report from eastern India that portrayed a landscape of co-appearing mutations in the non-Spike proteins, which might have led to the evolution of a distinct Delta subcluster. Accumulation of such mutations in SARS-CoV-2 may lead to the emergence of "vaccine-evading variants." Hence, monitoring of such non-Spike mutations will be significant in the formulation of any future vaccines against those SARS-CoV-2 variants that might evade the current vaccine-induced immunity, among both the pediatric and adult populations.