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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Virtual Screening of Novel Phytocompound(s) with Potential to Combat Mycobacterium tuberculosis Infection

Author(s): Anchal Aggarwal, Shilpa Sharma and Deepa Khare*

Volume 20, Issue 5, 2023

Published on: 11 August, 2022

Page: [570 - 580] Pages: 11

DOI: 10.2174/1570180819666220523152239

Price: $65

Abstract

Background: Tuberculosis is a worldwide health concern, and there is an immediate need for effective therapeutics to inhibit the infection caused by Mycobacterium tuberculosis. The persistent state of bacteria and the emergence of Multi-Drug Resistance are the two major reasons for the difficulty in treating tuberculosis.

Objective: The study aims to identify novel phytocompounds to effectively inhibit Mycobacterium tuberculosis by targeting the Esx-1 protein, which plays a vital function in the secretion pathway of M. tuberculosis to successfully disrupt the host cell and cause tuberculosis.

Methods: In the current study, ~500 novel phytocompounds were screened by docking against Esx-1 using AutoDock Vina 4.2 version. The visualization analysis for selected phytocompounds was performed using Protein-Ligand Interaction Profiler. A comparative study with a well-known drug for tuberculosis, Rifampicin, was also performed. Moreover, ADMET analysis was performed to check the druggability and pharmacokinetic parameters of the selected compounds.

Results: Based on the analysis, cadabicine, an alkaloid produced by Cadaba fruticose (Vizhuthi), Crataeva nurvala (Varuna) plants, exhibits the best binding affinity of -7.8 Kcal/mol with the active site residues, Leu 29 and Trp 43, of Esx-1, which are required for the stability of Esx-1 and virulence of M. tuberculosis in the host cell. ADMET analysis showed that cadabicine exhibits better druggability and pharmacokinetic parameters than other selected compounds.

Conclusion: Cadabicine possesses an acceptable binding affinity with the active site of Esx-1 and exhibits acceptable physicochemical and pharmacokinetic properties, which makes it a potential new drug candidate for the treatment of tuberculosis.

Keywords: Phytocompounds, Mycobacterium tuberculosis, small molecule inhibitors, Esx-1, type VII secretion system, cadabicine, Auto Dock Vina, ADMET analysis, PLIP, multiple drug resistance, extensive drug resistance.

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