Exploring the effects of novel inhibitors against malaria parasite invasion of human red blood cells

Abstract

Plasmodium falciparum accounts for the largest number of global malaria deaths each year. The blood stage of these parasites is responsible for the clinical symptoms of malaria and begins when merozoites invade red blood cells via a series of protein-protein interactions between the host and parasite. The binding of parasite ligand Reticulocyte-binding Protein Homologue 5 (RH5) to host receptor Basigin is essential for invasion and leads to a network of intracellular signalling events facilitating parasite entry. Interestingly, RH5-Basigin interaction can trigger a calcium (Ca2+) flux inside the red blood cell (RBC) and promote the phosphorylation of cytoskeletal proteins, suggesting that the parasites can exploit the biological activities of host proteins to drive invasion. Hence, inhibitors blocking the RH5-Basigin interaction are potentially effective against merozoite invasion into RBCs. The project aims to study the change in invasion patterns of these parasites using a list of small molecule inhibitors targeting the RH5-Basigin interaction. The compounds were screened virtually by our project partner, Atomwise®, before validation through in vitro experiment was carried out to measure the changes in RBC Ca2+ levels. Our findings showed that some molecules exhibit potential inhibitory effects, but further studies are still required to gain better insights into this novel therapeutic strategy against malaria.