Plasmepsins on the antimalarial hit list

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Science  27 Oct 2017:
Vol. 358, Issue 6362, pp. 445-446
DOI: 10.1126/science.aaq0002


The spread of multidrug-resistant “super malaria” throughout Southeast Asia (1, 2) offers another stern warning that new antimalarial drugs are needed urgently. Our present-day arsenal of antimalarials have poorly understood mechanisms of action, and no single drug targets all of the life-cycle stages of the malaria-causing parasite. Killing all life-cycle stages would stop parasite transmission between people and potentially prevent relapsing forms of malaria. On pages 522 and 518 of this issue, Pino et al. (3) and Nasamu et al. (4), respectively, identify different aspartyl protease inhibitor scaffolds as potent antimalarials that target multiple stages of the parasite life cycle. Importantly, they also identify the targets of these drugs and their essential functions in the malaria life cycle, exposing the underlying mechanisms of action. This provides two new enzymes to target with a combined therapy that could treat malaria.