In silico identification and validation of organic triazole based ligands as potential inhibitory drug compounds of SARS-CoV-2 main protease

Abstract

The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis, has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (M pro ). The SARS-CoV-2 main protease (M pro ) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (M pro ) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and they were then put through molecular dynamic (MD) simulation for stability, interaction and conformation analysis. In summary, we successfully identified the most suitable compounds for targeting SARS-CoV-2 main protease (M pro ). Based on our computational studies, we can suggest that the identified compounds can be used for further experimental approach as potential drug molecules against SARS-CoV-2.