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

Pantothenate synthetase protein plays a pivotal role in the biosynthesis of coenzyme A (CoA), which is a crucial molecule involved in a number of cellular processes including the metabolism of fatty acid, energy production, and the synthesis of various biomolecules, which is necessary 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 molecular dynamics (MD) simulation to identify promising phytochemical compounds targeting pantothenate synthetase for tuberculosis (TB) 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 100 ns MD simulation time. Furthermore, molecular mechanics generalized Born surface area (MM/GBSA) binding free energy calculations affirmed the stability of these three selected phytochemicals with binding energy ranges from -82.24 ± 9.35 to -66.83 ± 4.5 kcal/mol. Hence, these identified natural plant-derived compounds as potential inhibitors of pantothenate synthetase could be used to inhibit TB infection in humans.