(-)-Epigallocatechin-3-gallate demonstrates enhanced InhA binding affinity over isoniazid: a computational approach to anti-tuberculosis drug discovery

The persistent global health threat from Mycobacterium tuberculosis (Mtb), the cause of tuberculosis, is worsened by the rapid increase in drug-resistant strains, requiring the urgent development of new treatment approaches. This in silico study aimed to assess the inhibitory effects of tea polyphenols against Mycobacterium tuberculosis. A comprehensive computational method was employed, including target protein prediction, identification of common targets, protein-protein interaction analysis, and molecular docking. These tests were performed to accurately evaluate the binding affinity of tea polyphenols to the InhA protein, a key factor in Mtb survival and growth. The findings showed that EGCG has notable potential as an inhibitor of several essential Mtb proteins, such as enoyl-ACP reductase, methylated-DNA-protein-cysteine methyltransferase, daunorubicin-dim ABC transporter permeases DrrB and DrrC, and multidrug resistance ABC transporter permeases. Importantly, a network of interacting proteins was observed among EGCG-targeted proteins, suggesting potential synergistic effects. EGCG displayed strong binding affinity for the InhA protein and the multidrug transport system. Significantly, EGCG exhibited a higher binding affinity to InhA than isoniazid, with binding energies of -7.8 kcal/mol and -5.3 kcal/mol, respectively. Molecular docking of other tea catechins with InhA produced results comparable to those for InhA, further supporting the potential of these polyphenols as anti-tuberculosis agents. However, it is crucial to emphasize that these in silico findings must be validated through rigorous in vitro and in vivo studies to fully evaluate their therapeutic potential and clarify the exact mechanisms of action.