New Molecular Weapon Against Malaria

Malaria takes the lives of some 660,000 people each year, according to the World Health Organization. And because the Plasmodium parasites that cause the disease have begun developing resistance to drug treatments such as artemisinin, new antimalarial drugs are needed. To add therapies to the pipeline, a research team led by Michael K. Riscoe of the Veterans Affairs Medical Center, in Portland, Ore., has tested the safety and potency of a quinolone-3-diarylether compound known as ELQ-300 on both malaria parasites and infected mice (Sci. Transl. Med., DOI: 10.1126/scitranslmed.3005029). When the researchers fed infected mice a 1 mg/kg of body weight dose of the drug for four days, the compound cured the rodents. A single, lower dose given to noninfected mice prevented them from contracting malaria from disease-carrying mosquitoes. Like the antimalarial drug atovaquone, ELQ-300 kills malaria parasites by inhibiting the enzyme cytochrome bc₁, which enables the microorganisms to synthesize DNA building blocks. “We think that ELQ-300 acts at a different site on cytochrome bc₁ than atovaquone, however,” Riscoe says. This alternative interaction is likely responsible for the new drug’s heightened ability to evade the parasites’ evolving resistance: The team found that parasites treated with high concentrations of ELQ-300 developed no resistant strains over eight weeks, whereas parasites given atovaquone did so within 30 days.