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Updated: Apr 13, 2026

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
Published on: December 21, 2019
The novel compound Z060228 inhibits assembly of the HBV capsid
Hua Guan1, Guoming Zhao2, Wei Chen2
1Beijing Institute of Pharmacology and Toxicology, Beijing 100850, People's Republic of China; Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.
Aims:
The effective anti-HBV drugs on the market are mainly immunomodulators or nucleoside analogs. The uses of INF-α and lamivudine (3TC) are considerably limited by their low response rate, side effects, drug resistance and HBV recurrence. Thus, new mechanism-based drugs remain in urgent need. This study aimed to investigate the anti-HBV effects of the novel compound Z060228 and to confirm its anti-HBV mechanisms.
Main Methods:
HepG2.2.15 cells and HBV-transgenic mice were used to evaluate the anti-HBV activity of Z060228. Conformational changes of the capsid structure induced by Z060228 were detected with high-resolution electron microscopy (EM), size-exclusion chromatography (SEC), and atomic force microscopy (AFM).
Key Findings:
The HBV DNA replication in the supernatants of the HepG2.2.15 cells was effectively inhibited by Z060228 and Bay41-4109. In the liver of HBV-transgenic mice, the HBcAg content was significantly decreased and HBV DNA replication was also inhibited after high-dose (30 mg/kg) Z060228 treatment. Z060228 and Bay41-4109 exhibited similar effects on the self-assembly of Cp149. SEC data revealed that Z060228 altered the equilibrium (a state of stability) of Cp149 assembly. EM data further demonstrated that Z060228 could prevent Cp149 from self-assembling to the correct core particles. Additionally, AFM results showed that a low concentration of Z060228 caused Cp149 syncretizing, whereas a high concentration caused Cp149 to polymerize.
Significance:
Z060228 was demonstrated to be a potential capsid targeting anti-HBV drug candidate. The methods employed here could be used as a general strategy to study mechanisms of self-assembling protein-targeted drugs.
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