Process specific cellular screening for antimalarial drug discovery

Malaria continues to kill upwards of 400,000 people annually, and the development and spread of resistance to frontline drugs will put more lives at risk. For the malaria eradication campaign to succeed, we need next generation antimalarial drugs that do more than just treat disease. A versatile antimalarial would be capable of killing the clinically silent liver stage that initiates human infection, as well as the gametocytes which are responsible for transmitting infection back to mosquitos, in addition to killing the asexual blood stages that cause malaria. Phenotypic drug discovery has yielded new candidates meeting this highly desirable profile, and target identification and phenotypic profiiing have revealed that most of these abrogate the core parasite processes of protein production and transport. Development of process-specific screens to identify and differentiate those compounds able inhibit parasite protein synthesis and transport in their native cellular context, would accelerate the discovery of new high value antimalarials. This screening approach, while agnostic to molecular target, will allow use of a well-characterized model parasite to rapidly identify those compounds with the highest potential for being multistage inhibitors in a single primary screen.