National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China WHO Collaborating Centre for Tropical Diseases, Shanghai, China National Center for International Research on Tropical Diseases, Shanghai, China
Jun Li
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, Xinjiang, China
Wenjing Qi
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, Xinjiang, China Basic Medical College, Xinjiang Medical University, Urumqi, Xinjiang, China
Ying Chen
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China WHO Collaborating Centre for Tropical Diseases, Shanghai, China National Center for International Research on Tropical Diseases, Shanghai, China
Mengxiao Tian
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, Xinjiang, China Basic Medical College, Xinjiang Medical University, Urumqi, Xinjiang, China
Chuanchuan Wu
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, Xinjiang, China Basic Medical College, Xinjiang Medical University, Urumqi, Xinjiang, China
Yao Zhang
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, Xinjiang, China
Yingfang Yu
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China WHO Collaborating Centre for Tropical Diseases, Shanghai, China National Center for International Research on Tropical Diseases, Shanghai, China
Shuai Han
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China WHO Collaborating Centre for Tropical Diseases, Shanghai, China National Center for International Research on Tropical Diseases, Shanghai, China
Xiumin Han
Qinghai Provincial People's Hospital, Xining, Qinghai, China
Liping Duan
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China WHO Collaborating Centre for Tropical Diseases, Shanghai, China National Center for International Research on Tropical Diseases, Shanghai, China
Wenbao Zhang
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, Xinjiang, China
Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
