Antiviral effects of inhibiting host gene expression

RNA interference (RNAi) has been used to probe the virus-host interface to understand the requirements for host-gene expression needed for virus replication. The availability of arrayed siRNA libraries has enabled a genome-scale, high-throughput analysis of gene pathways usurped for virus replication. Results from these and related screens have led to the discovery of new host factors that regulate virus replication. While effective delivery continues to limit development of RNAi-based drugs, RNAi-based genome discovery has led to identification of druggable targets. These validated targets enable rational development of novel antiviral drugs, including the rescue and repurposing of existing, approved drugs. Existing drugs with known cytotoxicity and mechanisms of action can potentially be re-targeted to regulate host genes and gene products needed by influenza to replicate. Drug repositioning is more cost-effective, less time-consuming, and more effective for anti-influenza virus drug discovery than traditional methods. In this chapter, a general overview of RNAi screening methods, host-gene discovery, and drug repurposing is examined with emphasis on utilizing RNAi to identify druggable genes that can be targeted for drug development or repurposing.