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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Published in | iScience Vol. 25; no. 4; p. 104087 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
15.04.2022
Elsevier |
Subjects | |
Online Access | Get full text |
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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.
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•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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Lead contact |
ISSN: | 2589-0042 2589-0042 |
DOI: | 10.1016/j.isci.2022.104087 |