Journal article
Discovery of small molecule inhibitors of West Nile virus using a high-throughput sub-genomic replicon screen
Antiviral research, v 70(2), pp 39-50
2006
PMID: 16724398
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
West Nile virus (WNV) is a positive-sense, single-stranded RNA virus of the family Flaviviridae. WNV persistently infects insect cells, but can causes acute cytopathic infection of mammalian cells and is an etiologic agent of viral encephalitis in humans. By using a cell line expressing a WNV subgenomic replicon [Rossi, S.L., Zhao, Q., O’Donnell, V.K., Mason, P.W., 2005. Adaptation of West Nile virus replicons to cells in culture and use of replicon-bearing cells to probe antiviral action. Virology 331 (2), 457–470], we developed a high-throughput assay and used it to screen a library of small molecule compounds for inhibitors of WNV replication in the absence of live virus. Here we report the identification of novel small molecule inhibitors for WNV replicon replication. We demonstrate that the compounds inhibited WNV replication-dependent luciferase expression in the replicon cells and reduced WNV viral protein accumulation and viral RNA copy number in the replicon cells. Two classes of compounds with multiple hits, parazolotrahydrothophenes and pyrozolopyrimidines, showed preliminary structure–activity relationships. In WNV infection assays, one pyrozolopyrimidine compound was confirmed to have antiviral activity. These compounds should be valuable for developing anti-WNV therapeutic drugs as well as research tools to study the mechanism of WNV replication.
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Details
- Title
- Discovery of small molecule inhibitors of West Nile virus using a high-throughput sub-genomic replicon screen
- Creators
- Baohua Gu - Drexel UniversitySerguey Ouzunov - Drexel UniversityLiguan Wang - Drexel UniversityPeter Mason - The University of Texas Medical Branch at GalvestonNigel Bourne - The University of Texas Medical Branch at GalvestonAndy Cuconati - Institute for Hepatitis and Viral ResearchTimothy M. Block - Drexel University
- Publication Details
- Antiviral research, v 70(2), pp 39-50
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000237444300005
- Scopus ID
- 2-s2.0-33646468995
- Other Identifier
- 991019167609304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pharmacology & Pharmacy
- Virology