Designing Novel Inhibitors for Tuberculosis (Tb) by Targeting InhA and KasA Using Ligand Based Drug Design

Abstract

Tuberculosis (TB) is a contagious disease caused by bacteria called Mycobacterium tuberculosis, infects an estimated nearly one third of the world population has latent tuberculosis infection, as it has been documented according to the World Health Organization. The emergence of multidrug resistant varieties of Mycobacterium tuberculosis has led to a search for novel drug targets. We have performed an in silico comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen M. tuberculosis. Current therapy targets for TB treatment are based on the inhibiting of main proteins: the fatty-acid enoyl-acyl carrier protein reductase (InhA) and a complex of an acyl carrier protein (AcpM) and a β-ketoacyl-ACP synthase (KasA).  In this study novel inhibitor was designed against the proteins responsible for mycolic acid synthesis found in Mycobacterium tuberculosis. The ligands were screened using integrated computational protocol that relies on methods such as docking, in house method of “loop docking” and ADMET analysis. The ADMET analysis of the ligand indicated that it is likely to be a drug candidate.  It was observed that ligand with ID ZINC01757652 (Silybin) may prove to be a promising candidate drug for TB.