Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.

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 cos...

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Main Authors: Cristiana Lalli, Alessandra Guidi, Nadia Gennari, Sergio Altamura, Alberto Bresciani, Giovina Ruberti
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS Neglected Tropical Diseases
Online Access:http://europepmc.org/articles/PMC4312041?pdf=render
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spelling doaj-7c1546abac3041a693a6dedb91c45ed72020-11-25T00:08:00ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352015-01-0191e000348410.1371/journal.pntd.0003484Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.Cristiana LalliAlessandra GuidiNadia GennariSergio AltamuraAlberto BrescianiGiovina RubertiSchistosomiasis, 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.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.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.http://europepmc.org/articles/PMC4312041?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Cristiana Lalli
Alessandra Guidi
Nadia Gennari
Sergio Altamura
Alberto Bresciani
Giovina Ruberti
spellingShingle Cristiana Lalli
Alessandra Guidi
Nadia Gennari
Sergio Altamura
Alberto Bresciani
Giovina Ruberti
Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.
PLoS Neglected Tropical Diseases
author_facet Cristiana Lalli
Alessandra Guidi
Nadia Gennari
Sergio Altamura
Alberto Bresciani
Giovina Ruberti
author_sort Cristiana Lalli
title Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.
title_short Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.
title_full Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.
title_fullStr Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.
title_full_unstemmed Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.
title_sort development and validation of a luminescence-based, medium-throughput assay for drug screening in schistosoma mansoni.
publisher Public Library of Science (PLoS)
series PLoS Neglected Tropical Diseases
issn 1935-2727
1935-2735
publishDate 2015-01-01
description 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.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.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.
url http://europepmc.org/articles/PMC4312041?pdf=render
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