Computational investigation of thiol-reductase inhibitors to overcome amebiasis using Docking and SMD-based simulation analysis

Amoebiasis is an infectious disease caused by an intestinal parasitic protozon, Entamoeba histolytica. It is well known for invading and destroying human tissues, leading to life-threatening abscesses. To treatment of amoebiasis, and reduce the parasitic infection thioredoxin reductase (EhTrR), a promising target. It catalyzes the NADP-dependent reduction of amoebic thioredoxins, which is essential for maintaining intracellular redox balance. Therefore, in these studies, we selected 1150 FDA compounds and docked them with thioredoxin reductase. The best docked-score compounds were Betrixaban (-9.9 kcal/mol), Netrasudil (-9.6 kcal/mol), and Novobiocin (-9.4 kcal/mol), as well as positive control NADPH and negative control Metroindazole. Netrasudil is the best drug candidate for future use among these three compounds, according to the RMSD value, steered molecular dynamics, and interaction pattern. Before clinical trials and in vitro investigations, these substances might be used as thioreductase inhibitors.