In Silico Identification of Potential Inhibitors of Mycobacterium tuberculosis DNA Gyrase from Phytoconstituents of Indian Medicinal Plants

DNA gyrase, the sole type-II topoisomerase in Mycobacterium tuberculosis , plays a significant role in the bacteria’s survival by catalyzing the DNA topology change and is considered a crucial drug target. The emergence of drug resistance in Mycobacterium tuberculosis specifically against the second line of drugs; fluoroquinolones, targeting DNA gyrase, demands new potential compounds that would efficiently interact with it. To find a common suitable inhibitor for the apo and mutated forms of DNA gyrase, in this study, the compounds from an Indian medicinal plant database were screened for selecting potential drug-like molecules and two compounds IM5 and IM7 were selected after successful virtual screening and hit optimization with ADMET predictions, and chosen for MD simulation. The MMPBSA analysis of binding free energy validates the docking results of the two molecules. The principal component analysis also supported the stability of the complexes and thus, these two molecules have turned out to be promising candidates against Mycobacterium tuberculosis . Overall, this work sheds light on the potential of DNA gyrase inhibitors as therapeutic agents for Mycobacterium tuberculosis treatment, and IM5 and IM7 showed promise as future research compounds.