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

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

  • EBioMedicine. 2020 Apr;54:102711. doi: 10.1016/j.ebiom.2020.102711.
Jun Li 1,  Weisi Wang 2,  Junmin Yao 2,  Tian Wang 1,  Shizhu Li 2,  Wenjing Qi 1,  Shuai Han 2,  Yuan Ren 1,  Zhisheng Dang 2,  Xiumin Han 3,  Gang Guo 1,  Baoping Guo 1,  Liqin Wang 4,  Liping Duan 5,  Wenbao Zhang 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
  • 2 National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Centre for Tropical Diseases, Key Laboratory of Parasitology and Vector Biology of the Chinese Ministry of Health, Shanghai 200025, China.
  • 3 Qinghai Provincial People's Hospital, Xining 810007, China.
  • 4 Biotechnology Research Institute, Xinjiang Academy of Animal Science, Urumqi 830000, China.
  • 5 National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Centre for Tropical Diseases, Key Laboratory of Parasitology and Vector Biology of the Chinese Ministry of Health, Shanghai 200025, China; Qinghai Provincial People's Hospital, Xining 810007, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China. Electronic address: [email protected].
PMID: 32279056 DOI: 10.1016/j.ebiom.2020.102711
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 < 0.001). Using a microinjection of drug into cysts, pyronaridine (200 μM) showed highly effective in term of inhibition of cyst growth (p < 0.05, compared with saline group). Pharmacokinetic analysis revealed that pyronaridine was highly distributed in the liver and lungs, the most affected organs of CE. Function analysis showed that pyronaridine inhibited the activity of Topoisomerase I (IC50 = 209.7 ± 1.1 μM). In addition, classical apoptotic hallmarks, including DNA fragmentation and Caspase activation, were triggered.

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.

Keywords

Cystic echinococcosis; Drug repurposing; Echinococcus granulosus sensu stricto; Pyronaridine; Topoisomerase I.

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