A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways in <i>Plasmodium vivax</i> Hypnozoites.

ABSTRACT: Radical cure of Plasmodium vivax malaria must include elimination of quiescent 'hypnozoite' forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets for hypnozoites, we screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library and a collection of epigenetic inhibitors against P. vivax liver stages. From both libraries, we identified inhibitors targeting epigenetics pathways as selectively active against P. vivax and P. cynomolgi hypnozoites. These include DNA methyltransferase (DNMT) inhibitors as well as several inhibitors targeting histone post-translational modifications. Immunofluorescence staining of Plasmodium liver forms showed

SUBMITTER: Maher SP 

PROVIDER: S-EPMC9915689 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature