NAPE-PLD, a viable antimalarial drug target?

Abstract

The emergence of artemisinin-resistant strain of Plasmodium falciparum worsens global outlook of malaria as it impedes on the elimination of the disease. Due to added resistance, ring-stage parasite are becoming harder to eliminate, therefore exacerbating the need for novel ring-stage target for antimalarial treatments.In this study, we investigated N-acylphosphatidylethanolamine Phospholipase D (NAPEPLD) as a potential ring-stage target for treatment. It was found that the known inhibitors of NAPE-PLD, LEI-401 completely inhibited the parasite at the schizont and early ring stages, while ARN-19874 only partially inhibits. It was also revealed that NAPE-PLD may follow the PEXEL export pathway, as immunofluorescence assay suggests localisation in the parasitophorous vacuole membrane (PVM). Overall, the high IC50 of LEI-401 disqualifies it as an antimalarial treatment but may retain utility in elucidation of new drug targets.