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

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

  • Sci Data. 2022 Oct 8;9(1):610. doi: 10.1038/s41597-022-01733-4.
Dominik Olszewski  # 1,  Fanny Georgi  # 1,  Luca Murer 1,  Vardan Andriasyan 1,  Fabien Kuttler 2,  Anthony Petkidis 1,  Robert Witte 1,  Artur Yakimovich 3 4,  Lucy Fischer 1,  Alina Rozanova 1 5,  Yohei Yamauchi 5 6,  Gerardo Turcatti 2,  Urs F Greber 7
Affiliations

Affiliations

  • 1 Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland.
  • 2 Biomolecular Screening Facility, School of Life Sciences, Ecole Polytechnique Fédérale (EPFL) de Lausanne, Station 15, Lausanne, 1015, Switzerland.
  • 3 Center for Advanced Systems Understanding (CASUS), Helmholtz Center Dresden-Rossendorf, Untermarkt 20, 82026, Görlitz, Germany.
  • 4 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.
  • 5 University of Bristol, Bristol, BS8 1TH, United Kingdom.
  • 6 Institute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093, Zurich, Switzerland.
  • 7 Department of Molecular Life Sciences, University of Zurich (UZH), Winterthurerstrasse 190, 8057, Zurich, Switzerland. urs.greber@mls.uzh.ch.
  • # Contributed equally.
PMID: 36209289 DOI: 10.1038/s41597-022-01733-4
Abstract

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.

Figures
Products