Development and application of a high-throughput screening assay for identification of small molecule inhibitors of the P. falciparum reticulocyte binding-like homologue 5 protein
Brad E Sleebs, Kate E Jarman, Sonja Frolich, Wilson Wong, Julie Healer, Weiwen Dai, Isabelle S Lucet, Danny W Wilson, Alan F Cowman
International Journal for Parasitology: Drugs and Drug Resistance | ELSEVIER SCI LTD | Published : 2020
The P. falciparum parasite, responsible for the disease in humans known as malaria, must invade erythrocytes to provide an environment for self-replication and survival. For invasion to occur, the parasite must engage several ligands on the host erythrocyte surface to enable adhesion, tight junction formation and entry. Critical interactions include binding of erythrocyte binding-like ligands and reticulocyte binding-like homologues (Rhs) to the surface of the host erythrocyte. The reticulocyte binding-like homologue 5 (Rh5) is the only member of this family that is essential for invasion and it binds to the basigin host receptor. The essential nature of Rh5 makes it an important vaccine tar..View full abstract
Awarded by NHMRC
We thank the Red Cross Blood Service (Melbourne, Australia) for supply of blood and the Medicines for Malaria Venture for provision of the Malaria Box. This work was supported by the Victorian State Government Operational Infrastructure Support, Australian Government National Health and Medical Research Council (NHMRC) Independent Research Institute Infrastructure Support Scheme, the Australian Cancer Research Foundation and the NHMRC (grants 1057960 (A.F.C.), 637406 (A.F.C.), 1135421 (B.E.S.) and 1143974 (D.W.W)). B.E.S. is an Ellen Corin Fellow. A.F.C. is a Howard Hughes International Scholar. D.W.W. is a University of Adelaide Beacon Fellow. We thank Dr Kurt Lackovic, Dr Lin Chen and Dr Helene Jousset for helpful discussions.