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Journal article
An interferon-beta promoter reporter assay for high throughput identification of compounds against multiple RNA viruses
Antiviral research, v 107(1), pp 56-65
01 Jul 2014
PMID: 24792753
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Virus infection of host cells is sensed by innate pattern recognition receptors (PRRs) and induces production of type I interferons (IFNs) and other inflammatory cytokines. These cytokines orchestrate the elimination of the viruses but are occasionally detrimental to the hosts. The outcomes and pathogenesis of viral infection are largely determined by the specific interaction between the viruses and their host cells. Therefore, compounds that either inhibit viral infection or modulate virus-induced cytokine response should be considered as candidates for managing virus infection. The aim of the study was to identify compounds in both categories, using a single cell-based assay. Our screening platform is a HEK293 cell-based reporter assay where the expression of a firefly luciferase is under the control of a human IFN-beta promoter. We have demonstrated that infection of the reporter cell line with a panel of RNA viruses activated the reporter gene expression that correlates quantitatively with the levels of virus replication and progeny virus production, and could be inhibited in a dose-dependent manner by known antiviral compound or inhibitors of PRR signal transduction pathways. Using Dengue virus as an example, a pilot screening of a small molecule library consisting of 26,900 compounds proved the concept that the IFN-beta promoter reporter assay can serve as a convenient high throughput screening platform for simultaneous discovery of antiviral and innate immune response modulating compounds. A representative antiviral compound from the pilot screening, 1-(6-ethoxybenzo[d]thiazol-2-yl)-3-(3-methoxyphenyl) urea, was demonstrated to specifically inhibit several viruses belonging to the family of flaviviridae. (C) 2014 Elsevier B.V. All rights reserved.
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Details
- Title
- An interferon-beta promoter reporter assay for high throughput identification of compounds against multiple RNA viruses
- Creators
- Fang Guo - Drexel UniversityXuesen Zhao - Drexel Univ, Inst Biotechnol & Virol Res, Dept Microbiol & Immunol, Coll Med, Doylestown, PA 18902 USATina Gill - Drexel UniversityYan Zhou - Fox Chase Cancer CenterMatthew Campagna - Drexel UniversityLijuan Wang - Drexel UniversityFei Liu - Drexel UniversityPinghu Zhang - Drexel UniversityLaura DiPaolo - Drexel UniversityYanming Du - Baruch S. Blumberg InstituteXiaodong Xu - Baruch S. Blumberg InstituteDong Jiang - Peking UniversityLai Wei - Peking UniversityAndrea Cuconati - Baruch S. Blumberg InstituteTimothy M. Block - Baruch S. Blumberg InstituteJu-Tao Guo - Drexel UniversityJinhong Chang - Drexel University
- Publication Details
- Antiviral research, v 107(1), pp 56-65
- Publisher
- Elsevier
- Number of pages
- 10
- Grant note
- AI 104636 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AI113267 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Hepatitis B Foundation through the Commonwealth of Pennsylvania
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000338412500009
- Scopus ID
- 2-s2.0-84901058059
- Other Identifier
- 991019167570604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy
- Virology