Researchers from University of South Florida played a key role in an international multidisciplinary project that has yielded a promising new antimalarial drug with the potential to cure malaria and block its transmission with low doses.
Roman Manetsch, PhD, USF associate professor of
chemistry, and Dennis Kyle, PhD, USF professor of global health, were co-leaders of the USF team, which helped to discover and develop a series of potent compounds to combat malaria known as the 4-(1H)-quinolone-3-diarylethers, or quinolones.
The USF researchers were part of larger Medicines for Malaria Venture (MMV) project team including Oregon Health and Science University in Portland, Drexel University in Philadelphia, and Monash University in Australia.
The researchers narrowed the most effective drug candidates in the quinolones series to one lead drug – ELQ-300 – now moving toward clinical testing.
USF’s Alexis LaCrue, PhD, a research associate in Kyle’s laboratory, was a co-first author for the paper along with Aaron Nilsen, PhD, of Portland VA Medical Center.
In initial preclinical tests, the lead drug demonstrated impressive preventive and transmission-blocking – and a low likelihood for developing rapid resistance to major strains of malaria parasites.
In addition, ELQ-300 could likely be produced more cheaply than existing antimalarial drugs – a major advantage in treating a tropical disease that kills nearly one million people a year and causes recurring bouts of severe and incapacitating illness, most often among poor people in developing countries.
“This is one of the first drugs ever to kill the malaria parasite in all three stages of its life cycle,” Kyle, a member of the USF College of Public Health’s Global Infectious Diseases Research team said.
“So, it may become part of a new-generation therapy that not only treats sick people and prevents them from getting ill, but also blocks the transmission of malaria from mosquitoes to humans … If the drug can break the parasite life cycle, we may ultimately eradicate the disease,” he said.
The new drug class identified by the researchers were derived from the first antimalarial quinolone, endochin, discovered more than 60 years ago but never pursued as a treatment because it appeared not to work in humans.
Using new technology to optimize the quinolones, the MMV project team demonstrated that these compounds were indeed highly effective against Plasmodium falciparum, the most lethal strain of malaria, and Plasmodium vivax, the major cause of malaria outside Africa.
The quinolones target both the liver and blood stages of the parasite as well as the forms critical for disease transmission.
The findings are published in the journal Science Translational Medicine.
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