In silico targeting methylerythritol phosphate pathway IspD enzyme of Mycobacterium tuberculosis for novel anti-mycobacterial drug discovery

Abstract

The incidence of drug-resistant tuberculosis (TB) is the biggest challenge for the global TB control. Currently, resistance has been detected for almost all key anti-TB drugs. Therefore, an approach for a novel drug discovery with new targets is urgently required. A computational study was carried out to target 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase Isopentenyl pyrophosphate (IspD), an enzyme of the methylerythritol phosphate pathway that is essential for mycobacterial survival. Molecular docking was carried out with the available ligands using Discovery studio version 3.5. Among these ligands, rosuvastatin (RST) emerged as one of the suitable compounds against the enzyme that significantly interacted at the active site of the enzyme with the highest LibDock score of 121.08. Gly l6, Arg83, Thr84, and Thy190 are potential amino acid residues which contributed to the protein-ligand interaction. The significant interaction between IspD and RST suggested the potency of the ligand in curing TB.