title: Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.
abstract: BACKGROUND
  Schistosomiasis, one of the world's greatest neglected tropical diseases, is responsible for over 280,000 human deaths per annum. Praziquantel, developed in the 1970s, has high efficacy, excellent tolerability, few and transient side effects, simple administration procedures and competitive cost and it is currently the only recommended drug for treatment of human schistosomiasis. The use of a single drug to treat a population of over 200 million infected people appears particularly alarming when considering the threat of drug resistance. Quantitative, objective and validated methods for the screening of compound collections are needed for the discovery of novel anti-schistosomal drugs.
  
  
  RESULTS
  The present work describes the development and validation of a luminescence-based, medium-throughput assay for the detection of schistosomula viability through quantitation of ATP, a good indicator of metabolically active cells in culture. This validated method is demonstrated to be fast, highly reliable, sensitive and automation-friendly. The optimized assay was used for the screening of a small compound library on S. mansoni schistosomula, showing that the proposed method is suitable for a medium-throughput semi-automated screening. Interestingly, the pilot screening identified hits previously reported to have some anti-parasitic activity, further supporting the validity of this assay for anthelminthic drug discovery.
  
  
  CONCLUSIONS
  The developed and validated schistosomula viability luminescence-based assay was shown to be successful and suitable for the identification of novel compounds potentially exploitable in future schistosomiasis therapies.
authors: Institute of Cell Biology and Neurobiology, Campus A. Buzzati-Traverso, National Research Council, Monterotondo, Rome, Italy.
authors: Cristiana
authors: C
authors: Lalli
authors: Institute of Cell Biology and Neurobiology, Campus A. Buzzati-Traverso, National Research Council, Monterotondo, Rome, Italy.
authors: Alessandra
authors: A
authors: Guidi
authors: Department of Biology, IRBM Science Park xSpA, Pomezia, Rome, Italy.
authors: Nadia
authors: N
authors: Gennari
authors: Department of Biology, IRBM Science Park xSpA, Pomezia, Rome, Italy.
authors: Sergio
authors: S
authors: Altamura
authors: Department of Biology, IRBM Science Park xSpA, Pomezia, Rome, Italy.
authors: Alberto
authors: A
authors: Bresciani
authors: Institute of Cell Biology and Neurobiology, Campus A. Buzzati-Traverso, National Research Council, Monterotondo, Rome, Italy.
authors: Giovina
authors: G
authors: Ruberti
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D005260:Female; D008163:Luminescent Measurements; D051379:Mice; D012550:Schistosoma mansoni / Q000187:drug effects*; D012556:Schistosomicides / Q000494:pharmacology*
chemical_list: D012556:Schistosomicides; D000255:Adenosine Triphosphate
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