AUTHOR=Chouhan Mandeep , Tiwari Prashant Kumar , Mishra Richa , Gupta Saurabh , Kumar Mukesh , Almuqri Eman Abdullah , Ibrahim Nasir A. , Basher Nosiba Suliman , Chaudhary Anis Ahmad , Dwivedi Vivek Dhar , Verma Devvret , Kumar Sanjay 

TITLE=Unearthing phytochemicals as natural inhibitors for pantothenate synthetase in Mycobacterium tuberculosis: A computational approach

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1403900

DOI=10.3389/fphar.2024.1403900

ISSN=1663-9812

ABSTRACT=Pantothenate synthetase protein plays a pivotal role in the biosynthesis of coenzyme A (CoA), a crucial molecule involved in a number of cellular processes including metabolism of fatty acid, energy production, and the synthesis of various biomolecules, which is neccessary for the survival of Mycobacterium tuberculosis (Mtb). Therefore, inhibiting this protein, could disrupt CoA synthesis, leading to the impairment of vital metabolic processes within the bacterium, ultimately inhibiting its growth and survival. This study employed molecular docking, structure based virtual screening, and MD simulation to identify promising phytochemical compounds targeting pantothenate synthetase for tuberculosis treatment. Among 239 compounds, the top three (Rutin, Sesamin and Catechin gallate) were selected with binding energy values ranging from -11 to -10.3 kcal/mol, and the selected complexes showed RMSD (<3 Å) for 100ns MD simulation time. Furthermore, MM/GBSA binding free energy calculations affirmed the stability of these three selected phytochemicals with a binding energy ranges from -82.24±9.35 to -66.83±4.5 kcal/mol. Hence, these identified natural plant derived compound as potential inhibitor of pantothenate synthetase, could be utilized to inhibit tuberculosis infection in human.