Open Access

ARTICLE

Repurposing of FDA-Approved drugs to predict new inhibitors against key regulatory genes in Mycobacterium tuberculosis

XINJUN YANG¹, AFTAB ALAM², NAIYAR IQBAL³, KHALID RAZA^4,*

1 Department of Pediatrics, 3201 Hospital, Hanzhong, China
2 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
3 Department of Computer Science and Information Technology, Maulana Azad National Urdu University, Hyderabad, India
4 Department of Computer Science, Jamia Millia Islamia, New Delhi, India

* Corresponding Author: Khalid Raza,

BIOCELL 2021, 45(6), 1569-1583. https://doi.org/10.32604/biocell.2021.017019

Received 21 April 2021; Accepted 25 May 2021; Issue published 01 September 2021

Abstract

Tuberculosis (TB) disease has become one of the major public health concerns globally, especially in developing countries. Numerous research studies have already been carried out for TB, but we are still struggling for a complete and quick cure for it. The progress of Mycobacterium tuberculosis (MTB) strains resistant to existing drugs makes its cure and control very complicated. Therefore, it is the need of the hour to search for newer and effective drugs that can inhibit an increasing number of putative drug targets. We applied the drug repurposing concept to identify promising FDA-approved drugs against five key-regulatory genes (FurB, IdeR, KstR, MosR, and RegX3) of the MTB. The FDA drugs were virtually screened using a structure-based approach by GOLD versions 5.2, and subjected to rigid docking followed by an induced-fit docking algorithm to enhance the accuracy and prioritize drugs for repurposing. We found 11 candidate drugs (including ZINC03871613, ZINC03871614, ZINC03871615 as top scorer candidate drugs) that were frequently present within the top 20 GoldScore ranks and showed promising results. Furthermore, molecular dynamics simulation was performed to monitor the effect of the top scorer drugs on the structural stability of all the five targets, indicating that inhibitors preferentially bind to the active site of the targets. This work suggests that these known FDA-approved drugs open new application domains in the form of anti-tuberculosis agents.

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Keywords

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