The emergence and spread of drug resistance have hindered the campaign for malaria eradication. The development of new drug targets is a critical addition to our anti-malarial arsenal. Plasmepsins, which are aspartic proteases expressed by malaria parasites, serve important functions for parasite survival. Among the 10 members of this enzyme family, plasmepsin X (PMX) is essential for P. falciparum growth and has been shown to be involved in the egress of merozoites from infected red blood cells and the invasion of merozoites into red blood cells [1, 2]. Several aspartic protease inhibitors, including peptidomimetic substrate competitive inhibitors 49c  and 1SR , possess anti-malarial activity against P. falciparum and are shown to target PfPMX.
Here we describe an adapted parasite growth assay and show that 49c and 1SR affect P. knowlesi and P. falciparum in a similar manner. We will further investigate whether PMX is a cross-species target for antimalarial development. Using parasite growth assays and a ligand processing assay, we will determine how these PMX inhibitors affect P. knowlesi during parasite growth and examine the molecular mechanisms for plasmepsin inhibition.