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Assessment of FDA-approved drugs against Strongyloides ratti in vitro and in vivo to identify potentially active drugs against strongyloidiasis

Keiser, J. and Häberli, C.. (2021) Assessment of FDA-approved drugs against Strongyloides ratti in vitro and in vivo to identify potentially active drugs against strongyloidiasis. Parasit Vectors, 14. p. 615.

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Abstract

BACKGROUND: Infections with Strongyloides stercoralis belong to the most neglected helminth diseases, and research and development (R&D) efforts on novel drugs are inadequate. METHODS: A commercially available library containing 1600 FDA-approved drugs was tested in vitro against Strongyloides ratti larvae (L3) at 100 microM. Hits (activity > 70%) were then evaluated against S. ratti adult worms at 10 microM. Morantel, prasterone, and levamisole were tested in the S. ratti rat model using dosages of 1-100 mg/kg. RESULTS: Seventy-one of the 1600 compounds tested against S. ratti L3 revealed activity above 70%. Of 64 compounds which progressed into the adult screen, seven compounds achieved death of all worms (benzethonium chloride, cetylpyridinium chloride, Gentian violet, methylbenzethonium chloride, morantel citrate, ivermectin, coumaphos), and another eight compounds had activity > 70%. Excluding topical and toxic compounds, three drugs progressed into in vivo studies. Prasterone lacked activity in vivo, while treatment with 100 mg/kg morantel and levamisole cured all rats. The highest in vivo activity was observed with levamisole, yielding a median effective dose (ED50) of 1.1 mg/kg. CONCLUSIONS: Using a drug repurposing approach, our study identified levamisole as a potential backup drug for strongyloidiasis. Levamisole should be evaluated in exploratory clinical trials.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Helminth Drug Development (Keiser)
UniBasel Contributors:Keiser, Jennifer and Häberli, Cécile
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1756-3305 (Electronic)1756-3305 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:20 Dec 2022 10:07
Deposited On:20 Dec 2022 10:07

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