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Emerging Plasmodium resistance — including to artemisinin-based combination therapy — underlies a critical medical need for novel antimalaria therapies. Cyclophilins (chaperone proteins that possess peptidyl-proline isomerase activity) are encoded in the Plasmodium falciparum genome. While their precise roles are not known, their requirement for survival of Plasmodia (as well as the upregulation of PfCyclophilin 19B in artemisinin-resistant P. falciparum) identifies PfCyclophilin 19B as a potential drug target. Cyclosporin A exhibits antimalarial activity through cyclophilin inhibition, but its immunosuppressive properties limit its use. Alisporivir, a cyclosporin A analogue, is a second-generation cyclophilin inhibitor with activity agains…