Old drug repurposing for neglected disease: Pyronaridine as a promising candidate for the treatment of Echinococcus granulosus infections.

Abstract Background Cystic echinococcosis (CE), a condition caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu stricto, is a globally distributed zoonotic disease. Current treatment options for CE are limited, and an effective and safe anti-echinococcal drug is urgently required. Methods Drug repurposing strategy was employed to identify new therapeutic agents against echinococcal cysts. An in vitro protoscolicidal assay along with in vivo murine models was applied in the drug screening. A microinjection procedure was employed to mimic the clinical PAIR (puncture, aspiration, injection and reaspiration) technique to evaluate the potential application of the candidate drug in clinical practice. Findings We repurposed pyronaridine, an approved antimalarial drug, for the treatment of CE. Following a three-dose intraperitoneal regimen (57 mg/kg, q.d. for 3 days), pyronaridine caused 100% cyst mortality. Oral administration of pyronaridine at 57 mg/kg, q.d. for 30 days significantly reduced the parasitic burden in the pre-infected mice compared with albendazole group (p Interpretation Given its approved clinical safety, the repurposing of pyronaridine offers a rapidly translational option for treating CE including PAIR. Fund National Natural Science Foundation of China and International Cooperation Project of the Qinghai Science and Technology Department.