AI Article Synopsis
- New antiviral agents are needed for hepatitis B virus (HBV) treatment as current medications don't fully eliminate chronic infections.
- In this study, SRPK inhibitors SPHINX31, SRPIN340, and SRPKIN-1 showed varying degrees of anti-HBV activity, with SRPKIN-1 being the most effective in inhibiting HBV replication.
- SRPKIN-1 hinders the packaging of pregenomic RNA into capsids and affects the early stages of HBV infection, suggesting it could be a promising new treatment option.
Article Abstract
New antiviral agents are needed for the treatment of hepatitis B virus (HBV) infection because currently available drugs do not completely eradicate chronic HBV in patients. Phosphorylation dynamics of the HBV core protein (HBc) regulate several processes in the HBV life cycle, including nucleocapsid formation, cell trafficking, and virus uncoating after entry. In this study, the SRPK inhibitors SPHINX31, SRPIN340, and SRPKIN-1 showed concentration-dependent anti-HBV activity. Detailed analysis of the effects of SRPKIN-1, which exhibited the strongest inhibitory activity, on the HBV replication process showed that it inhibits the formation of infectious particles by inhibiting pregenomic RNA packaging into capsids and nucleocapsid envelopment. Mass spectrometry analysis combined with cell-free translation system experiments revealed that hyperphosphorylation of the C-terminal domain of HBc is inhibited by SRPKIN-1. Further, SRPKIN-1 exhibited concentration-dependent inhibition of HBV infection not only in HepG2-hNTCP-C4 cells but also in fresh human hepatocytes (PXB cells) and in the single-round infection system. Treatment with SRPKIN-1 at the time of infection reduced the nuclease sensitivity of HBV DNA in the nuclear fraction. These results suggest that SRPKIN-1 has the potential to not only inhibit the HBV particle formation process but also impair the early stages of viral infection.
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| http://dx.doi.org/10.1016/j.antiviral.2023.105756 | DOI Listing |
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