Antiviral drugs to cure and control malaria: towards resistance-proof, transmission-blocking drug combinations – HepCMal

New drug combinations are needed to regain control on malaria. Every year, malaria kills indeed more than 600,000, mainly children. Since 2015, the control of the pandemic has stalled and Plasmodium falciparum resistance to artemisinins, the major antimalarial medicines, has recently spread to Africa, epicenter of the disease. Efforts to eliminate malaria urgently require the development of new antimalarial combinations to cure mild and severe disease, eliminate artemisinin-resistant quiescent parasites, and prevent transmission. Complementing Artemisinin-based combination therapies with a drug enhancing these effects is considered a very effective approach.
Leveraging on our recent discovery that some anti-viral drugs are active against malaria parasites, our ambition is to design a drug combination that clears all parasites from the patient blood, and blocks their transmission to the mosquito vector. Our specific aims are to (i) determine which P. falciparum stages are sensitive to anti-viral drugs, (ii) identify the reference antimalarial drugs displaying synergy with these drugs, (iii) evaluate their efficacy against artemisinin-resistant quiescent parasites, (iv) confirm that they induce a sustained clearance of transmission parasite forms, and (v) Identify their target and mode of action on P. falciparum (likely different from their anti-viral target and mode of action). Add to Artemisinin-based Combination Therapies a safe drug able to simultaneously target quiescent parasite stages and transmissible gametocytes, is an innovative shift in the use of antimalarial drug combinations. Original knowledge is expected from the identification of the drug target and mode of action against the parasite. If positive, our results will support rapid testing in clinical trials, a process much faster than by a conventional development. Our cohesive translational consortium displays complementary expertise and skills to reach our common goals.