The complex of Plasmodium falciparum falcipain-2 protease with an (E)-chalcone-based inhibitor highlights a novel, small, molecule-binding site

Background Malaria kills over 400,000 people each year and nearly half the world’s population live in at-risk areas. Progress against malaria has recently stalled, highlighting the need for developing novel therapeutics. The parasite haemoglobin degradation pathway, active in the blood stage of the disease where malaria symptoms and lethality manifest, is a well-established drug target. A key enzyme in this pathway is the papain-type protease falcipain-2.