Computational assessment of Withania somnifera phytomolecules as putative inhibitors of Mycobacterium tuberculosis CTP synthase PyrG

Abstract

Genome evolution of Mycobacterium tuberculosis (Mtb) produces new strains resistant to various pre-existing anti-tubercular drugs. Hence, there is an urgent need to explore potent compounds with the most negligible side effects and effective Mtb inhibition. Mtb PyrG (CTP synthase) is a crucial enzyme for the conversion of the uridine triphosphate (UTP) into cytidine triphosphate (CTP) and is essential for the growth of Mtb. Thus, in this study, phytochemicals of Withania somnifera (W. somnifera) were screened to find the potential inhibitors against Mtb PyrG. Molecular docking resulted in the identification of quercetin 3-rutinoside-7-glucoside, rutin, chlorogenic acid and isochlorogenic acid C with a substantial docking score (from −12.6 to −10.8 kcal/mol) contributed by significant intermolecular interactions. Furthermore, 100 ns molecular dynamics simulation, ADME analysis and free binding energy calculations support the stability of docked complexes and drug-likeness for selected compounds, respectively. Collectively, these findings suggest that phytochemicals present in W. somnifera can be considered for further evaluation against Mtb in a series of in vitro and in vivo models.

Communicated by Ramaswamy H. Sarma

Keywords:

• Tuberculosis
• drug-resistant
• PyrG
• phytochemicals
• Withania somnifera
• MD simulations

Acknowledgments

Ankita Singh acknowledge University Grant Commission (UGC), India, for providing Junior research fellowship, and to the Director, AIRF, Jawaharlal Nehru University, New Delhi, India for giving access to Schrödinger suite. Sanjay Kumar acknowledge Council of Scientific and Industrial Research (CSIR), India, for providing senior research fellowship.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.