High-content, arrayed compound screens with rhinovirus, influenza A virus and herpes simplex virus infections.


Journal

Scientific data
ISSN: 2052-4463
Titre abrégé: Sci Data
Pays: England
ID NLM: 101640192

Informations de publication

Date de publication:
08 10 2022
Historique:
received: 15 05 2022
accepted: 28 09 2022
entrez: 8 10 2022
pubmed: 9 10 2022
medline: 12 10 2022
Statut: epublish

Résumé

Viruses are genetically and structurally diverse, and outnumber cells by orders of magnitude. They can cause acute and chronic infections, suppress, or exacerbate immunity, or dysregulate survival and growth of cells. To identify chemical agents with pro- or antiviral effects we conducted arrayed high-content image-based multi-cycle infection screens of 1,280 mainly FDA-approved compounds with three human viruses, rhinovirus (RV), influenza A virus (IAV), and herpes simplex virus (HSV) differing in genome organization, composition, presence of an envelope, and tropism. Based on Z'-factors assessing screening quality and Z-scores ranking individual compounds, we identified potent inhibitors and enhancers of infection: the RNA mutagen 5-Azacytidine against RV-A16; the broad-spectrum antimycotic drug Clotrimazole inhibiting IAV-WSN; the chemotherapeutic agent Raltitrexed blocking HSV-1; and Clobetasol enhancing HSV-1. Remarkably, the topical antiseptic compound Aminacrine, which is clinically used against bacterial and fungal agents, inhibited all three viruses. Our data underscore the versatility and potency of image-based, full cycle virus propagation assays in cell-based screenings for antiviral agents.

Identifiants

pubmed: 36209289
doi: 10.1038/s41597-022-01733-4
pii: 10.1038/s41597-022-01733-4
pmc: PMC9547564
doi:

Substances chimiques

Anti-Infective Agents, Local 0
Antiviral Agents 0
Mutagens 0
Aminacrine 78OY3Z0P7Z
Clobetasol ADN79D536H
Clotrimazole G07GZ97H65
Azacitidine M801H13NRU

Types de publication

Dataset Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

610

Subventions

Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : National Research Program
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 316030_170799 / 1
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 31003A_179256 / 1

Informations de copyright

© 2022. The Author(s).

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Auteurs

Dominik Olszewski (D)

Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Fanny Georgi (F)

Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Luca Murer (L)

Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Vardan Andriasyan (V)

Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Fabien Kuttler (F)

Biomolecular Screening Facility, School of Life Sciences, Ecole Polytechnique Fédérale (EPFL) de Lausanne, Station 15, Lausanne, 1015, Switzerland.

Anthony Petkidis (A)

Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Robert Witte (R)

Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Artur Yakimovich (A)

Center for Advanced Systems Understanding (CASUS), Helmholtz Center Dresden-Rossendorf, Untermarkt 20, 82026, Görlitz, Germany.
Bladder Infection and Immunity Group (BIIG), Department of Renal Medicine, Division of Medicine, University College London, Royal Free Hospital Campus, London, NW3 2PF, United Kingdom.

Lucy Fischer (L)

Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Alina Rozanova (A)

Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland.
University of Bristol, Bristol, BS8 1TH, United Kingdom.

Yohei Yamauchi (Y)

University of Bristol, Bristol, BS8 1TH, United Kingdom.
Institute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093, Zurich, Switzerland.

Gerardo Turcatti (G)

Biomolecular Screening Facility, School of Life Sciences, Ecole Polytechnique Fédérale (EPFL) de Lausanne, Station 15, Lausanne, 1015, Switzerland.

Urs F Greber (UF)

Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland. urs.greber@mls.uzh.ch.

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Classifications MeSH