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

The pantothenate synthetase protein is essential in the biosynthesis of coenzyme A (CoA), a critical molecule involved in various cellular processes such as fatty acid metabolism, energy production, and the synthesis of biomolecules necessary for the survival of Mycobacterium tuberculosis (Mtb). Inhibiting this protein can disrupt CoA synthesis, impairing vital metabolic BAL-0028 functions within the bacterium and ultimately hindering its growth and survival. This study utilized molecular docking, structure-based virtual screening, and molecular dynamics (MD) simulations to identify promising phytochemical compounds that target pantothenate synthetase for tuberculosis (TB) treatment. Out of 239 compounds, the top three—rutin, sesamin, and catechin gallate—were selected, with binding energy values ranging from -11 to -10.3 kcal/mol. These complexes exhibited RMSD values of less than 3 Å during a 100 ns MD simulation. Additionally, molecular mechanics generalized Born surface area (MM/GBSA) binding free energy calculations confirmed the stability of these phytochemicals, with binding energy values ranging from -82.24 ± 9.35 to -66.83 ± 4.5 kcal/mol. Therefore, these natural plant-derived compounds could serve as potential inhibitors of pantothenate synthetase, offering a new approach to combating TB infection in humans.