Effect of isoflavone agonists of IRF-3 on response to RNA viruses

There is a growing need for novel antiviral therapies that are broad-spectrum, effective, and not subject to resistance due to viral mutations. Using high-throughput screening methods, including computational docking studies and an ISG54-luciferase reporter assay, we identified a class of isoflavone compounds that act as specific agonists of innate immune signaling pathways and cause activation of the IRF-3 transcription factor. The objective of the microarray study was to examine the biological pathways associated with global gene expression changes following agonist treatment. Total RNA isolation and mRNA amplification were performed on equal masses of total RNA from MRC5 cells treated with either DMSO (negative control; n=3), or 10μM of the isoflavone agonist KIN 101 (n=3) at 20 hours post treatment. As a positive control for response to an RNA virus, total RNA isolation and mRNA amplification was performed on equal masses of total RNA from MRC5 cells infected with Sendai virus (n=3) at 20 hours post infection.