4.7 Article

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

Journal

ISCIENCE
Volume 25, Issue 4, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2022.104087

Keywords

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Funding

  1. Swiss National Science Foundation [CR32I2_166329]
  2. Swiss Commission for Technology and Innovation [25727.1]
  3. Swiss National Science Foundation (SNF) [CR32I2_166329] Funding Source: Swiss National Science Foundation (SNF)

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Schistosomiasis is a neglected tropical disease that affects a significant number of people annually. Due to the lack of effective drugs, repurposing compound libraries has become a viable option for accelerating drug development. A study using a high-throughput screening platform identified several potential drug candidates for the treatment of schistosomiasis.
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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