Comparative binding efficacy of Ivermectin and Remdesivir against the spike protein of Omicron variants: An in silico perspective

Abstract

The recent emergence of SARS-CoV-2 Omicron variants (B.1.1.529) has come out as an added complication in combating COVID-19. Different repurposed drugs like ivermectin, hydroxychloroquine, remdesivir, molnupiravir are being investigated to treat these variants. Herein, we investigate the comparative binding efficacy of ivermectin, remdesivir, hydroxychloroquine, favipiravir, paxlovid, and molnupiravir against the mutant spike protein of omicron variants. Molecular docking data revealed that ivermectin (∆G=-430.56) and remdesivir (∆G=-352.78) exhibit the higher binding efficacy to the spike protein mutants (N501Y, Q493R, Q498R, S373P, S375F, T478K, S371L, H655Y, N679K, P681H) of the Omicron variants, wild type SARS-CoV-2 and a hypothetical spike protein bearing all the mutations. Normal mode analysis and molecular dynamic simulation hinted at the stability of binding of ivermectin and remdesivir to spike protein mutant (T478K) compared to the less active drugs.This study highlights the significance of computational methods in enhancing drug discovery and repurposing through expedited analyses of molecular interactions, stability, and binding efficacy. It serves as an essential preliminary phase in pinpointing the potential therapeutic candidates for subsequent validation via in-vitro and in-vivo investigations. Collectively, this in silico study proposed that ivermectin and remdesivir could serve as promising therapeutics in intervening with the omicron variants.