Identification of a potent and specific retinoic acid-inducible gene 1 pathway activator as a Hepatitis B Virus antiviral through a novel cell-based reporter assay

Chronic Hepatitis B Virus (HBV) infection remains a global burden. To identify small molecule RIG -I agonists as antivirals against HBV, we developed an HBV-pgRNA-based interferon-beta (IFN-beta) luciferase reporter assay with high level of assay sensitivity, specificity and robustness. Through HTS screening, lead compound (JJ#1) was identified to activate RIG -I signaling pathway by inducing TBK1 phosphorylation. Knockdown experiments demonstrated that JJ#1-induced retinoic acid -inducible gene 1 (RIG -I) signaling pathway activation was MAVSdependent. Furthermore, JJ#1 exhibited HBV antiviral potency in HBV-infected cell models by reducing HBV DNA and antigens (HBsAg and HBeAg).