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

iScience

Bioengineering Laboratory, Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.

Published: April 2022

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 schistosomula in 128 microwells during 72 h to identify antischistosomal hits . 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976133PMC
http://dx.doi.org/10.1016/j.isci.2022.104087DOI Listing

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