Dominant Clade-featured SARS-CoV-2 Co-occurring Mutations Reveals Plausible Epistasis: An <i>in silico</i> based Hypothetical Model

ABSTRACT SARS-CoV-2 is evolved into eight fundamental clades where four (G, GH, GR, and GV) are globally prevalent in 2020. How the featured co-occurring mutations of these clades are linked with viral fitness is the main question here and we thus proposed a hypothetical model using in silico approach to explain the plausible epistatic effects of those mutations on viral replication and transmission. Molecular docking and dynamics analyses showed the higher infectiousness of a spike mutant through more favorable binding of G 614 with the elastase-2. RdRp mutation p.P323L significantly increased genome-wide mutations (p&lt;0.0001) since more flexible RdRp (mutated)-NSP8 interaction may accelerate replication. Superior RNA stability and structural variation at NSP3:C241T might impact protein and/or RNA interactions. Another silent 5’UTR:C241T…