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  • A fixed dose artemisinin-based combination therapy (ACT) consisting of artesunate, a semi-synthetic derivative of the sesquiterpine lactone, and pyronaridine, a benzonaphthyridine derivative, with anti-malarial and potential antiviral activities. Upon oral administration of artesunate/pyronaridine and hydrolysis of artesunate\'s active endoperoxide bridge moiety by liberated heme in parasite-infected red blood cells (RBCs), reactive oxygen species and carbon-centered radicals form, which damage and kill parasitic organisms. Pyronaridine inhibits the formation of beta-hematin, which results in the accumulation of toxic heme within the parasite. In addition, pyronaridine inhibits glutathione-dependent degradation of hematin. This promotes hematin-induced lysis of RBCs, resulting in parasite death. Artesunate/pyronaridine may also exhibit antiviral activity against some viruses by modulating the type-1 interferon (IFN) pathway.
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