A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria
Chahine Z, Abel S, Hollin T, Barnes G, Chung J, Daub M, Renard I, Choi J, Vydyam P, Pal A, Alba-Argomaniz M, Banks C, Kirkwood J, Saraf A, Camino I, Castaneda P, Cuevas M, De Mercado-Arnanz J, Fernandez-Alvaro E, Garcia-Perez A, Ibarz N, Viera-Morilla S, Prudhomme J, Joyner C, Bei A, Florens L, Ben Mamoun C, Vanderwal C, Le Roch K. A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria. Science 2024, 385: eadm7966. PMID: 39325875, DOI: 10.1126/science.adm7966.Peer-Reviewed Original ResearchConceptsP. falciparum malariaHumanized mouse modelPlasmodium falciparum</i> strainsIn vivo studiesParasite apicoplastDrug sensitivityTherapeutic profileVesicular traffickingGenomic analysisLipid biogenesisSecretory machineryAsexual replicationGenetic analysisReduced susceptibilityCellular traffickingApicoplast functionStrong efficacyMED6Sexual differentiationHemolytic activityDrug pipelineApicoplastKalihinolTraffickingMalariaIn vitro efficacy of next-generation dihydrotriazines and biguanides against babesiosis and malaria parasites
Vydyam P, Chand M, Gihaz S, Renard I, Heffernan G, Jacobus L, Jacobus D, Saionz K, Shah R, Shieh H, Terpinski J, Zhao W, Cornillot E, Mamoun C. In vitro efficacy of next-generation dihydrotriazines and biguanides against babesiosis and malaria parasites. Antimicrobial Agents And Chemotherapy 2024, 68: e00423-24. PMID: 39136469, PMCID: PMC11373198, DOI: 10.1128/aac.00423-24.Peer-Reviewed Original ResearchTherapeutic indexPlasmodium falciparum</i>Effective therapeutic strategyCausative agent of babesiosisIn vitro efficacyAntiparasitic drugsProtozoan parasitesMalaria parasitesIntraerythrocytic protozoan parasiteTherapeutic strategiesFolate pathwayBroad-spectrum antiparasitic drugStrain HB3Babesia divergensMalariaBabesia duncaniAnimal healthAntifolatesDrugWidespread resistanceCausative agentBiguanideBabesiaBabesiosisBiosynthesis of purines