Research ArticleMalaria

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance

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Science Translational Medicine  21 Jul 2021:
Vol. 13, Issue 603, eabg6013
DOI: 10.1126/scitranslmed.abg6013

Antimalarial advance

The need for antimalarial drugs is urgent in the face of growing resistance to existing therapies. Murithi et al. characterized MMV688533, an acylguanidine identified from compounds inhibiting known human drug targets that were screened for activity against Plasmodium falciparum. MMV688533 showed rapid in vitro killing of multiple P. falciparum strains as well as P. vivax. A single dose of MMV688533 rapidly reduced parasitemia in a P. falciparum NSG mouse model of infection, and this agent displayed favorable pharmacokinetic and toxicity profiles. MMV688533 selected for only low-grade resistance, with resistant parasites remaining sensitive to existing antimalarials. These findings suggest that MMV688533 is a promising antimalarial candidate with a low resistance risk and the promise of a single-dose cure, which merits further study.

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