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Current Computer-Aided Drug Design

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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

Natural Metabolite Ursolic Acid as an Inhibitor of Dormancy Regulator DosR of Mycobacterium tuberculosis: Evidence from Molecular Docking, Molecular Dynamics Simulation and Free Energy Analysis

Author(s): Babban Jee*, Prem Prakash Sharma, Vijay Kumar Goel, Sanjay Kumar, Yogesh Singh and Brijesh Rathi

Volume 19, Issue 6, 2023

Published on: 24 February, 2023

Page: [425 - 437] Pages: 13

DOI: 10.2174/1573409919666230201100543

Price: $65

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Abstract

Background: DosR is a transcriptional regulator of Mycobacterium tuberculosis (MTB), governing the expression of a set of nearly 50 genes that is often referred to as ‘dormancy regulon’. The inhibition of DosR expression by an appropriate inhibitor may be a crucial step against MTB.

Objective: We targeted the DosR with natural metabolites, ursolic acid (UA) and carvacrol (CV), using in silico approaches.

Methods: The molecular docking, molecular dynamics (MD) simulation for 200 ns, calculation of binding energies by MM-GBSA method, and ADMET calculation were performed to evaluate the inhibitory potential of natural metabolites ursolic acid (UA) and carvacrol (CV) against DosR of MTB.

Results: Our study demonstrated that UA displayed significant compatibility with DosR during the 200 ns timeframe of MD simulation. The thermodynamic binding energies by MM-GBSA also suggested UA conformational stability within the binding pocket. The SwissADME, pkCSM, and OSIRIS DataWarrior showed a drug-likeness profile of UA, where Lipinski profile was satisfied with one violation (MogP > 4.15) with no toxicities, no mutagenicity, no reproductive effect, and no irritant nature.

Conclusion: The present study suggests that UA has the potency to inhibit the DosR expression and warrants further investigation on harnessing its clinical potential.

Keywords: Mycobacterium tuberculosis, DosR, natural metabolite, ursolic acid, carvacrol, in silico approach.

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