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

J Virol Methods. 2024 Jan 2:114875. doi: 10.1016/j.jviromet.2023.114875. Online ahead of print.ABSTRACTChronic 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-β (IFN-β) 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 MAVS-dependent. Furthermore, JJ#1 exhibited HBV antiviral potency in HBV-infected cell models by reducing HBV DNA and antigens (HBsAg and HBeAg).PMID:38176614 | DOI:10.1016/j.jviromet.2023.114875
Source: Journal of Virological Methods - Category: Virology Authors: Source Type: research