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Development of a novel screening platform for the identification of small molecule inhibitors of human adenovirus.

Authors
  • Saha, Bratati1
  • Varette, Oliver2
  • Stanford, William L3
  • Diallo, Jean-Simon2
  • Parks, Robin J4
  • 1 Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada. , (Canada)
  • 2 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. , (Canada)
  • 3 Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada. , (Canada)
  • 4 Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada; Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada. Electronic address: [email protected] , (Canada)
Type
Published Article
Journal
Virology
Publisher
Elsevier
Publication Date
Dec 01, 2019
Volume
538
Pages
24–34
Identifiers
DOI: 10.1016/j.virol.2019.09.005
PMID: 31561058
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Human adenovirus (HAdV) can cause severe disease and death in both immunocompromised and immunocompetent patients. The current standards of treatment are often ineffective, and no approved antiviral therapy against HAdV exists. We report here the design and validation of a fluorescence-based high-content screening platform for the identification of novel anti-HAdV compounds. The screen was conducted using a wildtype-like virus containing the red fluorescent protein (RFP) gene under the regulation of the HAdV major late promoter. Thus, RFP expression allows monitoring of viral late gene expression (a surrogate marker for virus replication), and compounds affecting virus growth can be easily discovered by quantifying RFP intensity. We used our platform to screen ~1200 FDA-approved small molecules, and identified several cardiotonic steroids, corticosteroids and chemotherapeutic agents as anti-HAdV compounds. Our screening platform provides the stringency necessary to detect compounds with varying degrees of antiviral activity, and facilitates drug discovery/repurposing to combat HAdV infections. Copyright © 2019. Published by Elsevier Inc.

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