Genomic analysis of P falciparum strains with a mutation in the Plasmodium falciparum Na+ pump PfATP4

Small molecule inhibitors of PfATP4, a Plasmodium falciparum protein that is believed to pump Na+ out of the parasite while importing H+, are on track to become much-needed new antimalarial drugs. The spiroindolone cipargamin (KAE609) is poised to become the first PfATP4 inhibitor to be licensed for clinical use, having performed strongly in Phase 1 and 2 clinical trials. In a recent clinical trial for cipargamin, recrudescent parasites emerged, with most of these having a G358S mutation in PfATP4.