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Antimalarial angle The development of antimalarial compounds that target multiple stages of the Plasmodium falciparum life cycle remains a critical goal, especially in light of growing resistance to existing drugs. Istvan et al . exposed P. falciparum to thienopyrimidine compounds and observed rapid pan-life cycle parasite killing. Whole genome sequencing of parasite clones identified two mutations in the P. falciparum cytoplasmic isoleucyl tRNA synthetase (cIRS) associated with resistance to thienopyrimidines, and genetically modified parasites engineered with these mutations also showed resistance. Further analysis confirmed that cIRS inhibition by thienopyrimidine compounds is mediated by targeting a non-competitive allosteric binding site and functions differently than other known cIRS inhibitors. Together these findings highlight Plasmodium cIRS as a critical target for developing pan-life stage antimalarial compounds. —CF
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