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Background <p>High levels of circulating hepatitis B surface antigen (HBsAg) contribute to the dysfunction of the host immune response against HBV and the persistence of viral infection. This study aimed to investigate the effects and mechanisms of <i>Sophora alopecuroides</i> biflavones glycoside (SABG), isolated from the traditional herbal medicine <i>Sophora alopecuroides</i>, on HBV replication and HBsAg secretion.</p> Methods <p>To systematically evaluate the antiviral efficacy, a comprehensive set of experimental analyses was employed, including qPCR, RT-qPCR, ELISA, Western blot and particle gel assay. The DIA-based proteomic analysis, CETSA, molecular docking, and molecular dynamics simulation analyses were combined to explore the potential mechanisms.</p> Results <p>We discovered that SABG could not only remarkably inhibit intracellular level of HBV core DNA but also significantly reduce the extracellula<i>r</i> levels of HBV DNA, pgRNA, HBsAg and e antigen (HBeAg). Intriguingly, SABG had no impact on the intracellular levels of HBV pgRNA and core protein; instead, it caused abnormal accumulation of S protein. Further mechanistic studies revealed that SABG could bind directly to the antigenic loop (AGL) domain of HBs, thereby obstructing its post-translational cellular vesicle-based transport process. Finally, we observed a synergistic effect of SABG and lamivudine in the inhibition of intracellular level of HBV core DNA and the extracellular level of HBsAg.</p> Conclusion <p>Our studies reveal that SABG exhibits an antiviral activity against HBV by directly binding to the antigenic loop of surface protein, thereby impeding its secretion, which provides pharmacological evidence for the potential use of SABG as a candidate for the alternative treatment of HBV infection.</p>

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Sophora alopecuroides biflavones glycoside, isolated from Sophora alopecuroides, inhibits the secretion of hepatitis B virus surface antigen through direct interaction with its antigenic loop domain

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  • 发表日期：

    2025年10月27日

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  • Ya Wang,
  • Linlin Wang,
  • Ge Yang,
  • Lijun Qiao,
  • Rongmei Gao,
  • Huiqiang Wang,
  • Haiyan Yan,
  • Kun Wang,
  • Shuo Wu,
  • Hua Huang,
  • Yuhuan Li

摘要

Background

High levels of circulating hepatitis B surface antigen (HBsAg) contribute to the dysfunction of the host immune response against HBV and the persistence of viral infection. This study aimed to investigate the effects and mechanisms of Sophora alopecuroides biflavones glycoside (SABG), isolated from the traditional herbal medicine Sophora alopecuroides, on HBV replication and HBsAg secretion.

Methods

To systematically evaluate the antiviral efficacy, a comprehensive set of experimental analyses was employed, including qPCR, RT-qPCR, ELISA, Western blot and particle gel assay. The DIA-based proteomic analysis, CETSA, molecular docking, and molecular dynamics simulation analyses were combined to explore the potential mechanisms.

Results

We discovered that SABG could not only remarkably inhibit intracellular level of HBV core DNA but also significantly reduce the extracellular levels of HBV DNA, pgRNA, HBsAg and e antigen (HBeAg). Intriguingly, SABG had no impact on the intracellular levels of HBV pgRNA and core protein; instead, it caused abnormal accumulation of S protein. Further mechanistic studies revealed that SABG could bind directly to the antigenic loop (AGL) domain of HBs, thereby obstructing its post-translational cellular vesicle-based transport process. Finally, we observed a synergistic effect of SABG and lamivudine in the inhibition of intracellular level of HBV core DNA and the extracellular level of HBsAg.

Conclusion

Our studies reveal that SABG exhibits an antiviral activity against HBV by directly binding to the antigenic loop of surface protein, thereby impeding its secretion, which provides pharmacological evidence for the potential use of SABG as a candidate for the alternative treatment of HBV infection.