Parasite proteins targeted by Dihydroartemisinin (DHA-targeted proteins)

Parasite proteins targeted by Dihydroartemisinin (DHA) represent a diverse group of essential molecules within Plasmodium species that are susceptible to oxidative damage and covalent modification. The pharmacological activity of DHA is initiated by the cleavage of its internal endoperoxide bridge, a process catalyzed by iron or heme found within the parasite's food vacuole (Wang et al., 2015). This activation generates highly reactive carbon-centered radicals and reactive oxygen species (ROS) that indiscriminately alkylate nearby proteins, lipids, and nucleic acids (Ismail et al., 2016). Key targets identified through proteomic studies include enzymes involved in glycolysis, protein folding chaperones like PfHSP70, and transporters such as the calcium pump PfATP6 (Creek et al., 2008). This multi-target mechanism explains the drug's potent and rapid killing effect across multiple stages of the parasite life cycle (Tilley et al., 2016). However, the clinical utility of targeting these proteins is threatened by the emergence of resistance, which is primarily linked to mutations in the PfKelch13 protein that decrease the rate of hemoglobin degradation and subsequent drug activation (Tilley et al., 2016). Consequently, these proteins are central to the study of antimalarial efficacy and the ongoing challenge of drug resistance in global health.

Other names

Artemisinin-binding proteinsDHA-alkylated proteinsPlasmodium falciparum proteome (DHA-sensitive)Artemisinin-targeted parasite proteins

Dihydroartemisinin is activated by intra-parasitic heme or iron, leading to the formation of reactive oxygen species (ROS) and carbon-centered radicals that covalently alkylate and damage a broad spectrum of essential parasite proteins and lipids (Wang et al., 2015; Ismail et al., 2016).