Conference Agenda

Malaria remains a leading cause of morbidity and mortality, with 608,000 deaths reported in 2022, predominantly among children under five in sub-Saharan Africa. The disease, predominantly caused by Plasmodium falciparum, faces escalating challenges due to the emergence of strains resistant to all frontline antimalarials, including artemisinins. This highlights an urgent need for new therapeutic strategies. While de novo drug discovery is slow and costly, repurposing existing compounds offers a rapid and cost-effective alternative.
We screened the Structural Genomics Consortium’s Donated Chemical Probes Library, which consists of compounds originally developed for human diseases, to identify candidates with antimalarial potential. From 200 compounds, 11 demonstrated sub-micromolar potency against the P. falciparum Pf3D7 reference strain and retained activity across five resistant lines. Their equipotent profiles suggest novel mechanisms of action distinct from existing drug classes. In vitro pulse activity assays further characterized compound speed-of-action and asexual stage-specific antimalarial activity.
Future work will employ unbiased multi-omics approaches, including as untargeted metabolomics, solvent proteome profiling and limited-proteolysis mass spectrometry, to elucidate molecular targets and validate these candidates as starting points for drug development. These findings highlight the potential of compound repurposing to accelerate antimalarial discovery and identify new druggable pathways to combat resistance.