Identification of Potential Inhibitors of Cysteinyl tRNA Synthetase from Mycobacterium leprae TN Strain through in silico Virtual Screening.

Aminoacyl tRNA synthetases are believed to be a novel antibacterial, antifungal and antiparasitics targets due to their involvement in the process of protein translation. In this work, we have performed computer aided virtual screening of 14,400 compounds taken from Maybridge Hitfinder database and identified fourteen potential lead molecules for Cysteinyl tRNA synthetase of Mycobacterium leprae strain TN (MlCysRS). We have also performed docking of first-line antileprosy drugs such as dapsone, rifampicin and clofazimine with MlCysRS. The computational virtual screening and docking results show that these fourteen compounds have high binding affinity for MlCysRS. The top ranked compound, HTS11201, 7-[(3,4dichlorophenyl)methyl]-1,3-dimethyl-8-[2-(2-oxoindol-3-yl)hydrazinyl]purine-2,6-dione, has the binding score of 11.3 kcal/mol. Interestingly, eight strictly conserved residues from the catalytic domain of MlCysRS are involving in the formation of hydrogen bonding interactions with the lead molecules. Keyword: cysteinyl tRNA synthetase; Mycobacterium leprae; virtual screening; antibacterial drug target; molecular docking.