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New Approaches to Finding Next‐Generation Treatments for Malaria

Malaria still kills up to 1 million people annually. While malaria can be treated using different drug combinations, the constant emergence of resistant parasites means there is a continued need to place new compounds in the drug development pipeline. In addition to providing symptomatic relief, new drugs should have novel mechanisms of action to combat pre‐existing resistance. They should also prevent further malaria transmission, and eliminate latent‐stage parasites. Given that there are no known malaria drug targets that could yield a compound with this profile, we have been using cellular screening methods to find drug development leads that could eventually yield such medicines. These include screens designed to detect molecules active against malaria hepatic stages, the symptomatic blood stages and the parasite forms transmitted from humans to mosquitoes. We are using chemical genetics to work backwards to discover the targets of both promising leads for drug development, and tool compounds. Our unbiased efforts have resulted in the discovery of two completely novel small molecules that are currently in clinical trials for the treatment of malaria. In addition, the work is revealing a variety of novel parasite vulnerabilities.