Antiviral activity of novel chemical compound 0411, derived from FUBP1-IN-1 against hepatitis B virus by upregulation of DUSP5.

Current first-line drugs rarely achieve functional curesfor chronic hepatitis B patients, which urges us to explore novel anti-HBV therapeutic strategies. In this study, we found that the novel chemical compound 0411, a derivative of the FUBP1 inhibitor, FUBPI-IN-1, significantly suppressed HBV transcription both in vitro and in vivo. Transcriptome sequencing demonstrated that 0411 treatment markedly upregulated the expression of the dual-specificity phosphatase 5 (DUSP5) gene, a crucial regulator of the MAPK pathway. Further functional studies illustrated that the antiviral activity of compound 0411 was dependent on DUSP5. Mechanismly, 0411 treatment in HepG2-NTCP cells enhances the deposition of active histone modifications on the promoter of DUSP5 significantly. In conclusion, our findings demonstrate the potential of 0411 as an effective agent against HBV transcription.