Apigenin suppresses influenza A virus-induced RIG-I activation and viral replication

Apigenin is a flavonoid of low toxicity and multiple beneficial bioactivities, including the properties of antitumor, antioxidant, anti-inflammatory, and Antiviral activities. However, the effects of Apigenin on Influenza Virus infection remain poorly understood. Thus, the aim of this study is to investigate the effect of Apigenin on influenza A virus (IAV)-induced inflammation and viral replication. This study demonstrated that Apigenin treatment significantly suppressed IAV-induced upregulation of retinoic acid-inducible gene-I (RIG-I) expression, as well as the production of proinflammatory cytokines and interferons (IFN-β and IFN-λ1). Meanwhile, Apigenin also protected cells from IAV-induced cell death. In addition, Apigenin specifically inhibited the activation of RIG-I signaling via promoting the ubiquitin-mediated degradation of RIG-I, which may cause by the disrupting its interaction with heat shock protein 90α. Interestingly, instead of enhancing viral replication due to the inhibitory effects of Apigenin on the activation of RIG-I and expression of IFNs, Apigenin inhibited IAV replication in vitro. Further study demonstrated that Apigenin inhibited the influenza viral neuraminidase (NA) activity. Thus, Apigenin may serve as a promising supplementary approach for treatment of influenza because it protected cells from IAV-induced cell death and inhibited viral NA activity to suppress viral replication.