In silico analysis for the repurposing of broad-spectrum antiviral drugs against multiple targets from SARS-CoV-2: A molecular docking and ADMET approach

Abstract

Background: Amidst the second wave of COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led the world devastated, and resulted in the death of millions of people with its deadly virulence potential. In comparison to similar virus outbreaks, such as severe acute respiratory syndrome coronavirus (SARS CoV) and middle east respiratory syndrome coronavirus (MERS CoV), COVID-19 led to severe morbidity and mortality. Various therapeutic interventions to combat the SARS-CoV-2 infection are actively investigated, but still, there is no specific drug with high anti-viral efficacy against the SARS-CoV-2 virus has been reported yet. The present work is an effort to represent the promising therapeutic efficacy of 52 broad-spectrum anti-viral drugs as a potential lead molecule to suppress SARS-CoV-2 infection. These are the drugs that have shown potential efficacy against several viral infections earlier. The present article discusses the comparative analysis of the therapeutic efficacy of available broad-spectrum anti-viral drugs via assessment of receptor-ligand interaction using the molecular docking approach. Results: Based on the molecular docking indications, we predict the potential importance of various broad-spectrum antiviral drugs that can be repurposed for the treatment of SARS-CoV-2. Molecular docking revealed that Remedesivir, Imatinib, Herbacetin, Zanamivir, Ribavirin, Dasabuvir, Rhoifolin, Sofosbuvir, Cirsimaritin, and 2H-Cyclohepta[b]thiophene-3-carboxamide having strong interactions with respective targets. Conclusion: The present piece of work strongly recommends the anti-viral potential of Zanamivir for RdRp enzyme inhibition, Herbacetin against receptor binding domain of spike protein, and main protease target, Adefovir for ACE2, and Ribavirin for endoribonuclease active site. The current predictions will enhance the clinical development of potential therapeutic drugs to combat the pandemic significantly.