Target-based virtual screening and molecular dynamics approach to identify potential antileishmanial agents through targeting UvrD-like helicase ATP-binding domain

Background: About 0.7-1.0 million people worldwide have been suffering from Leishmaniasis. It falls under a neglected tropical disease (NTD) and is transmitted by biting infected female phlebotomine sandflies. The implication of "the NTD road map: together towards 2030" in the infection -prone regions worldwide has curtailed morbidity to a greater extent. However, limited options in antileishmanial oral and topical drugs must decipher more therapeutically efficacious agents to cure and eradicate the disease. Methods: Virtual screening based on structure, docking, & molecular dynamics approaches were adopted to identify potential lead molecules against UvrD-like helicase of Leishmania donovanifrom the MCULE database. Lipinski rule of five, N/O atoms (1-15), number of rings (1-2), HBDs (4-5), and HBAs (5-10) were applied as initial filters of SBVS. AutoDock Vina and GROMACS packages were used for docking and MD simulations, respectively. Results: Initial filters of SBVS workflow yielded 93885 ligand hits out of 100 plus million investigational ligands. Following the toxicology test, 28 ligands were gotten that were additional reduced to molecules (17) when accepted done the BOILED Egg model of the ADME. Six molecules were shortlisted with zero violation compliance of drug -likeness further than Lipinski RO5 viz., Egan, Veber, Muegge, Ghose, & bioavailability score having Delta G (-6.7 to -7.4 kcalmol(-1)) lesser than reference inhibitor miltefosine (-4.9 kcalmol(-1)). The stability of MCULE-5754880195-0-2 was found to be greater than the known inhibitor and ligand molecules mentioned above. Conclusion: MCULE-5754880195-0-2 has all therapeutic features by way of an admirable oral drug molecule & could be encouraging in Leishmaniasis prevention & treatment.