Specificity of GSK2606414 on PKR Function During Influenza Induced ER Stress

Influenza A viral (IAV) infections are a significant threat to public health, particularly due to the threat of intense immune response that can cause lung damage and secondary infections (Jiang & Zhang, 2023). As such, major areas of study, including viral replication and immune response, are crucial for developing molecules that target and limit the effect of infection. To address this, the Anathy laboratory is investigating the phosphorylation of PKR-like endoplasmic reticulum kinase (PERK), an endoplasmic reticulum (ER) protein that triggers cytokine/chemokine production in response to ER stress during IAV infection. Inhibition of PERK could lead to a decrease in tissue damage/secondary infections; however, it is structurally similar to protein kinase R (PKR), a protein that detects viral infection by binding to viral RNA and initiates an early host cell response. Distinguishing PERK from PKR using selective inhibition is imperative for therapeutic specificity and immune response (Raven & Koromilas, 2008).