Plasmodium falciparum parasites that are resistant to SW042

Malaria is one of the most common infectious illnesses in tropical underdeveloped nations, with significant morbidity and fatality rates. Plasmodium falciparum (Pf), the primary etiological agent, is spread by the bite of the female Anopheles mosquito. In the quest to find a new antimalarial, we conducted a cell-based phenotypic screen that led us to identify a series of novel compounds with anti-malarial activity. This chemical series of compounds showed enantiomer selectivity suggesting a specific protein target. Examination of compound-resistant clones of the Pf parasites, using whole genome sequencing identified point mutations in the proteasome active-site.