Abstract
The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.
Highlights
We demonstrated that antiarrhythmic drug amiodarone exhibits anthelmintic properties in a murine model of schistosomiasis, and this in vivo effect was associated with significant reductions in worm burdens and egg production, for early S. mansoni infections
From a phenotypic screening of 46 commercially available cardiovascular drugs, we found that the antiarrhythmic drug amiodarone exhibited antischistosomal properties with effective concentrations of 50% (EC50) value < 10 μM, which is below the clinically achievable plasma concentrations in vivo
Oral treatment with amiodarone was more effective than the gold-standard antiparasitic drug in mice harboring early S. mansoni infection
Summary
Schistosomiasis, known as snail fever and bilharzia, is a parasitic disease caused by infection with an intravascular trematode of the genus Schistosoma [1]. The disease infects approximately 230 million people, with more than 750 million at risk of infection, and results in significant mortality and devastating social and economic consequences [2]. Due to inflammation and fibrosis associated with eggs laid by the adult worms, can be painful and debilitating, hampering both personal productivity and community development. Schistosomiasis can cause anemia, malnutrition, growth stunting, intellectual retardation, and cognitive deficits [3]. Schistosoma mansoni is Pharmaceuticals 2021, 14, 686.
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