VIRTUAL SCREENING OF FDA-APPROVED DRUGS BY MOLECULAR DOCKING AND DYNAMICS SIMULATION TO RECOGNIZE POTENTIAL INHIBITORS AGAINST MYCOBACTERIUM TUBERCULOSIS ENOYL-ACYL CARRIER PROTEIN REDUCTASE ENZYME

HASANAIN ABDULHAMEED ODHAR; AHMED FADHIL HASHIM; SALAM WAHEED AHJEL; SUHAD SAMI HUMADI

doi:10.22159/ijap.2024v16i1.49471

Authors

HASANAIN ABDULHAMEED ODHAR Department of pharmacy, Al-Zahrawi University College, Karbala, Iraq https://orcid.org/0000-0002-5052-2080
AHMED FADHIL HASHIM Department of pharmacy, Al-Zahrawi University College, Karbala, Iraq
SALAM WAHEED AHJEL Department of pharmacy, Al-Zahrawi University College, Karbala, Iraq
SUHAD SAMI HUMADI Department of pharmacy, Al-Zahrawi University College, Karbala, Iraq

DOI:

https://doi.org/10.22159/ijap.2024v16i1.49471

Keywords:

Docking, Dynamics simulation, Repurpose, Mycobacterium tuberculosis, Enoyl-acyl carrier protein reductase, InhA

Abstract

Objective: This in silico study is aimed at identification of new possible inhibitors against Mycobacterium tuberculosis InhA enzyme by screening a library of FDA-approved drugs.

Methods: In this in silico study, a library of FDA-approved drugs was screened by molecular docking against the monomer of enoyl-acyl carrier protein reductase to recognize potential inhibitors. Then, those best drugs with minimum docking energy were subjected to molecular dynamics simulation.

Results: Out of the top ten docking hits, only revefenacin was able to maintain the closet proximity to InhA enzyme binding pocket during the two rounds of dynamics simulation. Analysis of molecular dynamics (MD) simulation data indicated that the antimuscarinic drug revefenacin has a ligand movement Root-Mean-Square Deviation (RMSD) that didn’t exceed 4 Angstrom. Also, in this MD study, revefenacin has a superior binding energy of -35.59 Kcal/mol as compared to -13.88 Kcal/mol for the other hit ergotamine. These favorable MD simulation records for revefenacin can be explained by its ability to continuously interact with enzyme binding pocket by two hydrogen bonds.

Conclusion: We report that the antimuscarinic drug revefenacin may have the potential to inhibit the enoyl-acyl carrier protein reductase for Mycobacterium tuberculosis. However, these preliminary results must be further evaluated by in vitro and in vivo studies.

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