The hematin-dihydroartemisinin adduct mobilizes a potent mechanism to suppress β-hematin crystallization.

ABSTRACT: Malaria remains a significant public health challenge in equatorial regions of the world, largely owing to the parasite's emerging resistance to the recently introduced drugs of the artemisinin (ART) family. In the human body, most ART-derivative drugs are metabolized to dihydroartemisinin (DHA), which, in the parasite, after activation by heme, can form a hematin-dihydroartemisinin adduct (H-DHA). Here we test whether and how H-DHA inhibits hematin crystallization, the main constituent of the heme detoxification pathway of malaria parasites. We find that H-DHA is a poor inhibitor of classical crystal growth-it weakly blocks the growth sites on crystal surfaces-and, counterproductively, a promoter of β-hematin nucleation, driven by a boost in the formation of precursors. We establish that

SUBMITTER: Azargoshasb H 

PROVIDER: S-EPMC12271862 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature