Insilico Insights into Resveratrol as a Potential Inhibitor of Mycobacterium Tuberculosis Enoyl-ACP Reductase (InhA) Protein

Insilico Insights into Mycobacterium Tuberculosis Enoyl-ACP Reductase

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a global cause of death. Thus, the development of innovative treatment strategies is required. Objective: To develop in-silico drugs by phytochemicals to inhibit the Enoyl-ACP reductase (InhA) protein, which is essential for synthesizing mycobacterial cell walls. Methods: The 3D structure of InhA was taken from the Protein Data Bank. The Ramachandran plot validated the model with a score of 98.7% from the favoured Ramachandran plot. Computed Atlas of Surface Topography of Proteins was used to detect the active sites for ligand interaction. Resveratrol were selected based on existing studies and further listed for drug-likeness. Absorption, Distribution, Metabolism, Excretion, and Toxicity analysis showed the possibility of resveratrol as a drug candidate, with no violation of Lipinski rules and excellent absorption in the Gastrointestinal Tract. Results: The boiled egg model confirmed the ability of ligands to go through the blood-brain barrier. Toxicity predictions of resveratrol indicated low risks with several other systems of organs. Molecular docking with CB-Dock2 showed the strong binding of Resveratrol to InhA, with a Vina score equal to -8.8 kcal/mol. Further exploration of the docking complex by molecular docking simulation using the Integrated Management of the Public Distribution System was carried out, and the trajectory confirmed stable interaction and protein flexibility. Conclusions: It was concluded that resveratrol acts as a potent, non-toxic candidate for tuberculosis treatment and highlights its inhibition capacity of InhA. Results need future vitro and in vivo validation to develop this highly reliable therapeutic alternative for combating tuberculosis.