The researchers screened 400 compounds for the Malaria Box project, one of the first open-source drug discovery efforts to combat infectious diseases
The USF Center for Global Health and Infectious Diseases Research was among 55 groups worldwide to participate in a Medicines for Malaria Venture initiative to help catalyze drug discovery for malaria and other neglected diseases. The center is based in the USF College of Public Health.
A paper appearing in the journal PLoS Pathogens describes the results of the organization’s Malaria Box project. The project involved 55 groups, including USF’s, which were provided open access to 400 diverse molecules with confirmed activity against the Plasmodium falciparum malaria parasite. Using a wide variety of biological assays, the researchers screened the commercially available compounds to help select the most promising candidates for further testing in mouse models and medicinal chemistry programs.
“One of the most difficult problems with drug discovery is finding a good starting point, a good chemical compound with the potential to lead to a drug,” said Dr. Dennis Kyle, a Distinguished USF Health Professor at the time of the project. “In this study collaborators from around the world tested 400 drug and probe-like compounds for multiple diseases and indications to identify essential starting points that will lead to future drugs to treat the most neglected infectious diseases of mankind.”
Dr. Kyle’s laboratory, which could high-throughput screen as many as 7,500 compounds in 72 hours, tested the safety and effectiveness of all 400 compounds against the brain-eating amoeba Naegleria fowleri.
Microscopic image of the brain-eating amoeba Naegleria fowleri
In addition, Dr. John Adams, Distinguished University Professor; Dr. Rays Jiang, assistant professor of global health; and Dr. Kyle profiled Plasmodium falciparum transposon mutant clones with drug-like compounds from the Malaria Box collection. The USF researchers looked for similarities in mechanisms of action with those of artemisinin drugs, the current frontline antimalarial treatments. The USF researchers’ data analysis, combined with that of other groups, is shared in the PLoS Pathogens publication.
The USF group is now a collaborator in the Pathogen Box project, also spearheaded by the Medicines for Malaria Venture. The project is analyzing a second collection of 400 compounds targeting neglected tropical diseases, including malaria, cryptosporidiosis, leishmaniasis, lymphatic filariasis, onchoceriasis (river blindness), and tuberculosis.
To learn more about research opportunities addressing malaria and other infectious diseases, visit the USF College of Public Health Department of Global Health.