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Updated: Aug 14, 2026

Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
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A New Role of Class A Hepatitis B Virus Capsid Assembly Modulators in Core Protein Dynamics and Covalently Closed

Chunkyu Ko1, Xue Zhou2, Romina Bester3

  • 1Institute of Virology, Technical University of Munich, Helmholtz Munich, Munich, Germany; Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.

Cellular and Molecular Gastroenterology and Hepatology
|August 12, 2026
PubMed

Insights

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) like HAP_R01 disrupt HBV core protein assembly, leading to insoluble protein accumulation and reduced viral replication. This novel mechanism offers a new therapeutic strategy for chronic hepatitis B.

Area of Science:

  • Hepatology and Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • Current chronic hepatitis B treatments are rarely curative.
  • Capsid assembly modulators (CAMs) target hepatitis B virus (HBV) core protein assembly.
  • Class A CAMs (CAM-A) induce abnormal core protein assembly, but their precise mechanism and effect on HBV replication are not fully understood.

Purpose of the Study:

  • To investigate the mechanism of action of CAM-A molecule HAP_R01.
  • To analyze the effects of HAP_R01 on HBV core protein dynamics, capsid assembly, and viral replication.
  • To evaluate the therapeutic potential of HAP_R01 in HBV-infected models.

Main Methods:

  • Infection of human liver chimeric mice and HBV-susceptible cells.
  • Monitoring of HBV core protein and capsid dynamics under HAP_R01 treatment over four weeks.
  • Analysis of HBV virus and protein dynamics, including localization, solubility, and accumulation of core protein.

Main Results:

  • HAP_R01 altered HBV core protein's nuclear-cytoplasmic distribution, confirmed in primary human hepatocytes and liver-humanized mice.
  • HAP_R01 targeted newly synthesized core protein, affecting assembly, localization, and solubility in a dose- and time-dependent manner.
  • Treatment with HAP_R01 reduced HBV covalently closed circular DNA (cccDNA) pool and suppressed HBsAg and HBeAg secretion by inhibiting cccDNA replenishment.

Conclusions:

  • HAP_R01, a CAM-A, inhibits HBV replication by disrupting capsid assembly.
  • HAP_R01 induces insoluble core protein accumulation in the nucleus, impacting cccDNA pool replenishment.
  • Perturbing capsid assembly and inducing core protein aggregation represents a promising therapeutic strategy for chronic hepatitis B.
Abstract

Keywords:
CapsidCapsid Assembly ModulatorsCore ProteinHepatitis B Virus

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