Screening Assay for Anticancer and Antiviral Drugs

The goal is to develop an assay to identify potential antiviral and anticancer compounds. Theassay is based on the activity of the cellular enzyme PKR (Protein Kinase RNA-activated). PKR is inducedby interferon and requires double-stranded RNA for activation. Activated PKR inhibits translation. Byinhibiting translation the cell stops viral replication since viruses are dependent on host translation. Someviruses (adenovirus, vaccinia virus, rotavirus, reovirus, poliovirus, influenza, and possibly HIV) haveevolved mechanisms to counteract this anti viral system by inhibiting PKR. The fact that manypathogenic viruses have inhibitors of PKR suggests that inhibition of this enzyme is important for viralreplication. In addition to its anti viral effects, PKR may also function as a suppressor of cell proliferationand tumor formation. Though tightly regulated, PKR apparently must be expressed and activated attimes during the cell cycle. In this context, activators of PKR may be useful as antitumorigeniccompounds, since activation could inhibit translation, perhaps leading to growth suppression of thetumor. The assay described here is a simple assay of PKR activity that can be adapted to identifyactivators of PKR, or to identify compounds that block viral inhibitors of PKR.