2024
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 pipelineApicoplastKalihinolTraffickingMalaria
2021
Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal Infection
Chiu JE, Renard I, Pal AC, Singh P, Vydyam P, Thekkiniath J, Kumar M, Gihaz S, Pou S, Winter RW, Dodean R, Frueh L, Nilsen AC, Riscoe MK, Doggett JS, Mamoun C. Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal Infection. Antimicrobial Agents And Chemotherapy 2021, 65: 10.1128/aac.00662-21. PMID: 34152821, PMCID: PMC8370247, DOI: 10.1128/aac.00662-21.Peer-Reviewed Original ResearchConceptsEndochin-like quinolonesLethal infectionBlood-borne diseasesBlood-borne pathogensEffective therapyRelated apicomplexan parasitesExperimental therapiesLow doseMouse modelInfectious agentsHuman infectionsInfectionClinical candidatesStrong efficacyB. microtiExcellent safetyMode of actionTherapyErythrocytic developmentAtovaquoneEfficacyApicomplexan parasitesSafetyStructure-activity relationshipsParasitemia