In Silico Investigation of Komaroviquinone as a Potential Inhibitor of Sars-Cov-2 Main Protease (Mpro): Molecular Docking, Molecular Dynamics, and Qm/Mm Approaches

30 Pages Posted: 30 May 2023

See all articles by Samuel José Mendes dos Santos

Samuel José Mendes dos Santos

Federal Institute of Education, Science and Technology of Rio Grande do Sul

Antoninho Valentini

Federal University of Ceara

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.

Note:

Funding Information: This study was funded by the Instituto Federal do Rio Grande do Sul and also by personal contributions from the authors.

Competing Interests: All authors of this manuscript declare no conflicts of interest in connection with the research reported in this paper.

Keywords: SARS-Cov-2, Covid-19, Komaroviquinone, Mpro, QM/MM.

Suggested Citation

Santos, Samuel José Mendes dos and Valentini, Antoninho, In Silico Investigation of Komaroviquinone as a Potential Inhibitor of Sars-Cov-2 Main Protease (Mpro): Molecular Docking, Molecular Dynamics, and Qm/Mm Approaches. Available at SSRN: https://ssrn.com/abstract=4456125 or http://dx.doi.org/10.2139/ssrn.4456125

Samuel José Mendes dos Santos (Contact Author)

Federal Institute of Education, Science and Technology of Rio Grande do Sul ( email )

Porto Alegre
Brazil

Antoninho Valentini

Federal University of Ceara ( email )

Rua Papi Júnior 1225 - Rodolfo Teófilo
Fortaleza, 60431970
Portugal

Do you have a job opening that you would like to promote on SSRN?

Paper statistics

Downloads
32,042
Abstract Views
2,150
Rank
130
PlumX Metrics