Putative Inhibitor of TcCYP51 from a Library of Approved Drugs: A Virtual Screening Study

Chagas disease is a public health problem, particularly in Latin America. The available treatment consists of two poorly effective drugs in the chronic phase of this parasitic disease. Considering the lack of effective treatment, alternatives are sought, such as the search focused on the biological targets of the etiologic agent. Based on this strategy, the role of Trypanosoma cruzi sterol 14α-demethylase (TcCYP51) in ergosterol seems promising. In this work, we apply the virtual screening approach to a proposal to repurpose U.S. Food and Drug Administration (FDA) approved drugs. We combined computational techniques and used rigorous validation to identify putative inhibitors from the FDA-approved drug library. The results indicated one of these drugs as a putative inhibitor of the TcCYP51 enzyme.

Keywords:
Trypanosoma cruzi; 14α-demethylase; virtual screening; molecular docking; ROC curve; QSAR