In silico investigation of Komaroviquinone as a potential inhibitor of SARS-CoV-2 main protease (Mpro): Molecular docking, molecular dynamics, and QM/MM approaches

Abstract

COVID-19 has highlighted the urgent need for new therapeutic agents to combat the spread of the virus. The main protease of SARS-CoV-2 (Mpro) has emerged as a promising target. In this study, we conducted an in silico investigation to explore the potential of Komaroviquinone, an icetexane diterpene, as a therapeutic agent against COVID-19. We employed molecular docking, molecular dynamics, and QM/MM methodologies to compare the binding affinity, molecular interactions, and stability of Komaroviquinone and the FDA-approved antiviral drug Nirmatrelvir with the SARS-CoV-2 Mpro protein. The study demonstrated that Komaroviquinone exhibits strong interaction with Mpro, with a binding energy comparable to Nirmatrelvir. The ADMET analysis revealed that Barbatusol, Brussonol, and Komaroviquinone possess superior solubility, permeability, and intestinal absorption compared to Nirmatrelvir, as well as more favorable distribution properties and lower toxicity profiles. Notably, Nirmatrelvir displayed toxicity and hepatotoxicity, which were not present in the natural compounds. Thus, it is suggested that Komaroviquinone may be a promising candidate for the development of effective and safer therapeutic agents against COVID-19. Experimental validation is necessary to confirm its potential as a treatment for the disease.