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Updated: Mar 24, 2026

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
Transcriptional analysis of antiviral small molecule therapeutics as agonists of the RLR pathway
R R Green1, C Wilkins1, S Pattabhi2
1Department of Immunology, and the Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, WA, USA.
Abstract:
The recognition of pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRR) during viral infection initiates the induction of antiviral signaling pathways, including activation of the Interferon Regulator Factor 3 (IRF3). We identified small molecule compounds that activate IRF3 through MAVS, thereby inhibiting infection by viruses of the families Flaviviridae (West Nile virus, dengue virus and hepatitis C virus), Filoviridae (Ebola virus), Orthomyxoviridae (influenza A virus), Arenaviridae (Lassa virus) and Paramyxoviridae (respiratory syncytial virus, Nipah virus) (1). In this study, we tested a lead compound along with medicinal chemistry-derived analogs to compare the gene transcriptional profiles induced by these molecules to that of other known MAVS-dependent IRF3 agonists. Transcriptional analysis of these small molecules revealed the induction of specific antiviral genes and identified a novel module of host driven immune regulated genes that suppress infection of a range of RNA viruses. Microarray data can be found in Gene Expression Omnibus (GSE74047).
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