Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries

Schistosomiasis is a neglected tropical disease that affects over 200 million people annually. As the antischistosomal drug pipeline is currently empty, repurposing of compound libraries has become a source for accelerating drug development, which demands the implementation of high-throughput and ef...

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Bibliographic Details
Published iniScience Vol. 25; no. 4; p. 104087
Main Authors Ravaynia, Paolo S., Biendl, Stefan, Grassi, Francesco, Keiser, Jennifer, Hierlemann, Andreas, Modena, Mario M.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 15.04.2022
Elsevier
Subjects
Biotechnology
Drugs
Microbiology parasite
Monitoring feature
Signal processing
Drugs
Signal processing
Biotechnology
Microbiology parasite
Monitoring feature
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Summary:Schistosomiasis is a neglected tropical disease that affects over 200 million people annually. As the antischistosomal drug pipeline is currently empty, repurposing of compound libraries has become a source for accelerating drug development, which demands the implementation of high-throughput and efficient screening strategies. Here, we present a parallelized impedance-based platform for continuous and automated viability evaluation of Schistosoma mansoni schistosomula in 128 microwells during 72 h to identify antischistosomal hits in vitro. By initially screening 57 repurposed compounds against larvae, five drugs are identified, which reduce parasite viability by more than 70%. The activity profiles of the selected drugs are then investigated via real-time dose-response monitoring, and four compounds reveal high potency and rapid action, which renders them suitable candidates for follow-up tests against adult parasites. The study shows that our device is a reliable tool for real-time drug screening analysis of libraries to identify new promising therapeutics against schistosomiasis. [Display omitted] •Scalable, plastic microwell chip with integrated platinum electrodes•Automated impedance-based recording of 128 microwell units in parallel•Continuous monitoring of in vitro drug library efficacy on schistosomula for 72 h•Identification of four fast-acting antischistosomal drugs for in vivo testing Biotechnology; Drugs; Microbiology parasite; Monitoring feature; Signal processing
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2022.104087