Identification of Potential Inhibitors for Fasciola hepatica Glutathione Transferase Using Molecular Docking and Virtual Screening

Abstract

Fasciola hepatica, the parasitic flatworm responsible for fascioliasis, a serious neglected tropical disease, remains a serious threat to human and animal health worldwide. The parasite's glutathione transferase (GST) enzyme plays a crucial role in detoxifying xenobiotics and endogenous compounds and is therefore a desirable target for drug action.

This study used molecular docking and virtual screening approaches to screen for potential small-molecule inhibitors of F. hepatica GST, the aim of finding novel anti-fascioliasis drug leads. 100 compounds were screened from the ZINC database for FDA-approved drugs. Molecular docking simulations were performed to determine the binding affinities of the ligands for the GST active site, where a number of potential candidates emerged. The highly ranked ligands showed high binding affinities with primary interactions in the form of hydrogen bonding, electrostatic interactions, and hydrophobic forces. Among these, the highest binding energy of -8.4 kcal/mol was associated with (ZINC000026664090), revealing its lead status for potential development into a new drug. Such findings provide crucial information on how to design efficacious inhibitors against F. hepatica GST and represent a bright direction for future development of fascioliasis therapeutics.