Volume 92, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Single-dose therapies for malaria have been proposed as a way to reduce the cost and increase the effectiveness of antimalarial treatment. However, no compound to date has shown single-dose activity against both the blood-stage parasites that cause disease and the liver-stage parasites that initiate malaria infection. Here, we describe a subset of cytochrome (cyt ) inhibitors, including the novel 4(1)-quinolone ELQ-400, with single-dose activity against liver, blood, and transmission-stage parasites in mouse models of malaria. Although cyt inhibitors are generally classified as slow-onset antimalarials, we found that a single dose of ELQ-400 rapidly induced stasis in blood-stage parasites, which was associated with a rapid reduction in parasitemia in vivo. ELQ-400 also exhibited a low propensity for drug resistance and was active against atovaquone-resistant strains with point mutations in cyt . Ultimately, ELQ-400 shows that cyt inhibitors can function as single-dose, blood-stage antimalarials and is the first compound to provide combined treatment, prophylaxis, and transmission blocking activity for malaria after a single oral administration. This remarkable multi-stage efficacy suggests that metabolic therapies, including cyt inhibitors, may be valuable additions to the collection of single-dose antimalarials in current development.


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  • Received : 01 Sep 2014
  • Accepted : 13 Feb 2015
  • Published online : 03 Jun 2015

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