Designing of Plasmodium Falciparum Leucyl Aminopeptidase Inhibitors for Substrate Ingress/Egress Path Using Virtual Screening

摘要

Plasmodium falciparum leucyl aminopeptidase (PfAM17) is an attractive anti-malarial drug target. Discovery of PfAM17 inhibitors has been focused on targeting the active site. Nonspecificity and off target activity of known aminopeptidase inhibitorslimit their use as an antimalarial drug.Therefore, identifying newPfA-M17 inhibitors which function through a different mechanismcould complement current drug design strategies and improve drugefficacy. In this study, we explored a novel binding site of PfA-M17and identified new PfA-M17 inhibitors through receptor based virtualscreening. A library of 244,839 compounds were screened usingreceptor-based virtual screening against the predicted cavity of PfAM17, and three levels of accuracy were used: high-throughput virtualscreening, grid-based ligand docking with energetics (Glide)standard precision and Glide extra precision. Our findings reveal anew drug targeting site for malaria therapy.