Anti-HBV therapeutic potential of small molecule 3,5,6,7,3′,4′-Hexamethoxyflavone in vitro and in vivo

Current treatment methods for hepatitis B are mainly antiviral drug therapy and immunotherapy, in which antiviral drugs are mainly nucleoside analogue and interferon. They can significantly reduce the viral load but rarely achieve hepatitis B surface antigen (HBsAg) loss. 3,5,6,7,3',4'-Hexamethoxyflavone was screened out from a small molecule compound library for its lower cytotoxic effect and greater HBsAg inhibition activity. Meanwhile, we further performed experiments in HepG2.2.15, HepG2-NTCP cells, PHHs and HBV transgenic mouse model to evaluate the anti-HBV effects of 3,5,6,7,3',4'-Hexamethoxyflavone. Our study found that 3,5,6,7,3',4'-Hexamethoxyflavone can significantly reduce the level of HBV RNAs, HBV DNA and HBsAg, in addition, the activity of four HBV promoters and the ratio of total RNAs/cccDNA and 3.5 kb RNA/cccDNA were decreased by 3,5,6,7,3',4'-Hexamethoxyflavone. Mechanistically, we found HNF3 alpha plays important roles in Hex mediated HBV transcription inhibition. Our study indicated Hex was a potential anti-HBV therapeutic drug.

Automated summary

3,5,6,7,3',4'-Hexamethoxyflavone showed anti-HBV effects by reducing HBV RNA, HBV DNA, and HBsAg levels, as well as inhibiting HBV promoter activity and altering the RNA/cccDNA ratio. The compound has the potential to be a therapeutic drug for hepatitis B virus.