Screening the Medicines for Malaria Venture Pathogen Box for invasion and egress inhibitors of the blood stage of Plasmodium falciparum reveals several inhibitory compounds
Madeline G Dans, Greta E Weiss, Danny W Wilson, Brad E Sleebs, Brendan S Crabb, Tania F de Koning-Ward, Paul R Gilson
International Journal for Parasitology | ELSEVIER SCI LTD | Published : 2020
With emerging resistance to frontline treatments, it is vital that new drugs are identified to target Plasmodium falciparum. One of the most critical processes during parasites asexual lifecycle is the invasion and subsequent egress of red blood cells (RBCs). Many unique parasite ligands, receptors and enzymes are employed during egress and invasion that are essential for parasite proliferation and survival, therefore making these processes druggable targets. To identify potential inhibitors of egress and invasion, we screened the Medicines for Malaria Venture Pathogen Box, a 400 compound library against neglected tropical diseases, including 125 with antimalarial activity. For this screen, ..View full abstract
Awarded by (NHMRC), Australia
Awarded by NHMRC
Awarded by (National Health and Medical Research Council (NHMRC)), Australia
This work was supported by the Victorian Operational Infrastructure Support Program, Australia received by the Burnet Institute, Australia. We acknowledge Medicines for Malaria Venture (MMV) for providing access to the MMV Pathogen Box and the Australian Red Cross Blood Bank for the provision of human blood. M.G.D is a recipient of an Australian Government Research Training Program Scholarship, G.E.W a Peter Doherty - Australian Biomedical Fellowship, B.E.S a Development Grant 1113712, (National Health and Medical Research Council (NHMRC)), Australia, D.W.W and B.E.S (NHMRC), Australia, Project Grant APP1143974, and T.F.dK.-W. a NHMRC Senior Research Fellowship (APP1136300). B.E.S. is a Corin Centenary Fellow (Walter and Eliza Hall Institute (WEHI)), Australia, D.W.W is a University of Adelaide, Australia, Beacon Fellow, B.S.C a Program Grant 1092789 (NHMRC). We thank Alan Cowman, WEHI, Australia, for providing the R1 peptide and Monash Micro Imaging, Australia for assistance with microscopy.