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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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Autores principales: Ravaynia, Paolo S., Biendl, Stefan, Grassi, Francesco, Keiser, Jennifer, Hierlemann, Andreas, Modena, Mario M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976133/
https://www.ncbi.nlm.nih.gov/pubmed/35378863
http://dx.doi.org/10.1016/j.isci.2022.104087
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author Ravaynia, Paolo S.
Biendl, Stefan
Grassi, Francesco
Keiser, Jennifer
Hierlemann, Andreas
Modena, Mario M.
author_facet Ravaynia, Paolo S.
Biendl, Stefan
Grassi, Francesco
Keiser, Jennifer
Hierlemann, Andreas
Modena, Mario M.
author_sort Ravaynia, Paolo S.
collection PubMed
description 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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spelling pubmed-89761332022-04-03 Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries Ravaynia, Paolo S. Biendl, Stefan Grassi, Francesco Keiser, Jennifer Hierlemann, Andreas Modena, Mario M. iScience Article 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. Elsevier 2022-03-16 /pmc/articles/PMC8976133/ /pubmed/35378863 http://dx.doi.org/10.1016/j.isci.2022.104087 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Ravaynia, Paolo S.
Biendl, Stefan
Grassi, Francesco
Keiser, Jennifer
Hierlemann, Andreas
Modena, Mario M.
Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries
title Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries
title_full Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries
title_fullStr Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries
title_full_unstemmed Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries
title_short Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries
title_sort real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976133/
https://www.ncbi.nlm.nih.gov/pubmed/35378863
http://dx.doi.org/10.1016/j.isci.2022.104087
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