A computational approach to evaluate critical Spike protein mutations in non-synonymous variants of SARS-CoV-2

The third outbreak of severe acute respiratory syndrome caused by coronavirus (SARS-CoV-2) was reported in December 2019 by the WHO (World Health Organization) in Wuhan (China). Until today (07/2022), the pandemic has resulted in more than 560 million confirmed cases and more than 6 million deaths¹. The present work combines molecular modeling methods (structural analysis, homology modeling, molecular docking, and virtual screening) with bioinformatics techniques (biological database manipulation, multiple alignments and analysis of large datasets of sequences) to examine the effects of non-synonymous variations (NSVs) in the lineages of concern (α, β, δ, γ), which are present in the receptor binding domain (RBD) of the Spike structural protein. The influence exerted by NSVs on the RBD-Host interaction interface between ligand candidates and critical amino acids present in the binding domain resulted in different impacts on the protein structure and, consequently, on the virtual screening classification of potential drugs for repurposing².