Details

Autor(en) / Beteiligte

• Ravaynia, Paolo S.
• Biendl, Stefan
• Grassi, Francesco
• Keiser, Jennifer
• Hierlemann, Andreas
• Modena, Mario M.

Titel

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

Ist Teil von

• iScience, 2022-04, Vol.25 (4), p.104087-104087, Article 104087

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Freely accessible e-journals

Beschreibungen/Notizen

• 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