Myricetin supresses HBV replication both in vitro and in vivo via inhibition of HBV promoter SP2

Abstract

Hepatitis B virus (HBV) infection remains a significant global public health concern. Myricetin, a flavonoid compound widely distributed in natural plants, has demonstrated multiple biological functions in combating diseases such as cancer and inflammation. In this research, we explored the mechanism of myricetin against HBV replication. We employed various experiments such as ELISA, Southern Blot, Northern Blot, Western Blot, RT-qPCR, Dual luciferase reporter gene assay, ChIP, EMSA, IHC, Immunofluorescence, AAV infection, and isolation of primary human hepatocytes (PHH) in this study. Our results showed that myricetin significantly reduced the expression of HBV markers, including HBsAg, HBeAg and covalently closed circular DNA (cccDNA), in HepG2-NTCP cells and PHH. We further confirmed these findings using AAV-HBV cell and mouse models. Furthermore, we found that myricetin significantly downregulated HBV SP2 promoter activity. Mechanistically, myricetin reduced CEBPA expression, which in turn interfered with the binding of CEBPA to the HBV SP2 promoter, leading to an antiviral effect. In conclusion, myricetin exhibited promising antiviral activity against HBV, suggesting its potential for novel HBV treatment.

Keywords: CCAAT/Enhancer-binding protein alpha (CEBPA); Hepatitis B virus (HBV); Myricetin; cccDNA.