Scientific Associate VP
Merck Research Laboratories
Neglected Tropical Diseases Discovery Lead
Twists and turns in drug discovery: An antimalarial drug discovery case study that deciphers unique biology and identifies a potent development drug candidate.
Malaria is a devastating disease that directly effects over half a million people each year with the most devastating and debilitating effects on young children. Antimalarial drug discovery by and large is focused on the identification of novel drugs to treat and prevent the disease due to the emergence and spread of Plasmodium strains resistant to existing medicines. In particular, artemisinin resistance which has now spread from SE Asia and is firmly established in Africa (as reported at ASTMH in Seattle Oct 2022).
Merck, a large pharmaceutical company, paired up with an academic collaborator, Professor Alan Cowman and his colleagues to do some malaria parasite drug hunting. The resulting collaboration identified robust targeted aspartyl protease screening hits that required some creative biochemical target identification to nail down the exact mechanism of the molecules. With some expert medicinal chemistry and detailed biological deciphering the team ended up with dual targeting molecules that are functionally active during the liver, blood and mosquito stage of the parasite’s replication cycle.