Metabolic adaptations of hemoparasites: coenzyme A and polyamine biosynthesis pathways as drug targets

Hemoparasites such as Plasmodium, Babesia, and Theileria species present significant global health and veterinary challenges, but their intracellular lifestyle within host erythrocytes reveals promising opportunities for targeted therapies by exploiting their dependence on host nutrients. Pantothenate-coenzyme A (CoA) biosynthesis and polyamine metabolism continue to generate strong interest as potential drug targets, with recent genetic, biochemical, and metabolomic studies highlighting compelling species- and life stage-specific differences in pathway architecture, essentiality, and redundancy that guide precise therapeutic strategies. This review integrates current knowledge on pantothenate acquisition, CoA biosynthesis, and polyamine synthesis or salvage across these hemoparasites, emphasizing validated metabolic vulnerabilities suitable for drug development, highlighting areas where findings differ across studies, and recognizing how metabolic plasticity and host scavenging inspire effective interventions. These insights highlight the need for rigorous, stage-specific experimental validation to advance parasite metabolism as a foundation for novel antiparasitic drugs.