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A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus

Human adenoviruses (HAdVs) are fatal to immuno-suppressed individuals, but no effective anti-HAdV therapy is available. Here, we present a novel image-based high-throughput screening (HTS) platform, which scores the full viral replication cycle from virus entry to dissemination of progeny and second...

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Autores principales: Georgi, Fanny, Kuttler, Fabien, Murer, Luca, Andriasyan, Vardan, Witte, Robert, Yakimovich, Artur, Turcatti, Gerardo, Greber, Urs F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423605/
https://www.ncbi.nlm.nih.gov/pubmed/32788590
http://dx.doi.org/10.1038/s41597-020-00604-0
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author Georgi, Fanny
Kuttler, Fabien
Murer, Luca
Andriasyan, Vardan
Witte, Robert
Yakimovich, Artur
Turcatti, Gerardo
Greber, Urs F.
author_facet Georgi, Fanny
Kuttler, Fabien
Murer, Luca
Andriasyan, Vardan
Witte, Robert
Yakimovich, Artur
Turcatti, Gerardo
Greber, Urs F.
author_sort Georgi, Fanny
collection PubMed
description Human adenoviruses (HAdVs) are fatal to immuno-suppressed individuals, but no effective anti-HAdV therapy is available. Here, we present a novel image-based high-throughput screening (HTS) platform, which scores the full viral replication cycle from virus entry to dissemination of progeny and second-round infections. We analysed 1,280 small molecular weight compounds of the Prestwick Chemical Library (PCL) for interference with HAdV-C2 infection in a quadruplicate, blinded format, and performed robust image analyses and hit filtering. We present the entire set of the screening data including all images, image analyses and data processing pipelines. The data are made available at the Image Data Resource (IDR, idr0081). Our screen identified Nelfinavir mesylate as an inhibitor of HAdV-C2 multi-round plaque formation, but not single round infection. Nelfinavir has been FDA-approved for anti-retroviral therapy in humans. Our results underscore the power of image-based full cycle infection assays in identifying viral inhibitors with clinical potential.
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spelling pubmed-74236052020-08-18 A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus Georgi, Fanny Kuttler, Fabien Murer, Luca Andriasyan, Vardan Witte, Robert Yakimovich, Artur Turcatti, Gerardo Greber, Urs F. Sci Data Data Descriptor Human adenoviruses (HAdVs) are fatal to immuno-suppressed individuals, but no effective anti-HAdV therapy is available. Here, we present a novel image-based high-throughput screening (HTS) platform, which scores the full viral replication cycle from virus entry to dissemination of progeny and second-round infections. We analysed 1,280 small molecular weight compounds of the Prestwick Chemical Library (PCL) for interference with HAdV-C2 infection in a quadruplicate, blinded format, and performed robust image analyses and hit filtering. We present the entire set of the screening data including all images, image analyses and data processing pipelines. The data are made available at the Image Data Resource (IDR, idr0081). Our screen identified Nelfinavir mesylate as an inhibitor of HAdV-C2 multi-round plaque formation, but not single round infection. Nelfinavir has been FDA-approved for anti-retroviral therapy in humans. Our results underscore the power of image-based full cycle infection assays in identifying viral inhibitors with clinical potential. Nature Publishing Group UK 2020-08-12 /pmc/articles/PMC7423605/ /pubmed/32788590 http://dx.doi.org/10.1038/s41597-020-00604-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the metadata files associated with this article.
spellingShingle Data Descriptor
Georgi, Fanny
Kuttler, Fabien
Murer, Luca
Andriasyan, Vardan
Witte, Robert
Yakimovich, Artur
Turcatti, Gerardo
Greber, Urs F.
A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus
title A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus
title_full A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus
title_fullStr A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus
title_full_unstemmed A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus
title_short A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus
title_sort high-content image-based drug screen of clinical compounds against cell transmission of adenovirus
topic Data Descriptor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423605/
https://www.ncbi.nlm.nih.gov/pubmed/32788590
http://dx.doi.org/10.1038/s41597-020-00604-0
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