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D-cycloserine, a potential candidate for reducing Hepatitis B virus cccDNA in vitro
Yongwook Choi1, Yong Kwang Park1, Wonhee Hur2
1Division of Chronic Viral Disease Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Chungbuk, South Korea.
Journal of Virological Methods
|April 30, 2025
Summary
Researchers developed a new system to screen for drugs targeting Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA). D-cycloserine effectively reduced HBV antigens and degraded cccDNA, offering a promising therapeutic strategy.
Area of Science:
- Hepatology
- Virology
- Drug Discovery
Background:
- Hepatitis B virus (HBV) infection persists due to covalently closed circular DNA (cccDNA).
- HBV cccDNA is a primary risk factor for chronic liver disease, including cirrhosis and hepatocellular carcinoma.
- Eradicating HBV cccDNA is crucial for preventing liver disease progression.
Purpose of the Study:
- To establish a novel drug screening system for identifying agents targeting HBV cccDNA.
- To evaluate the efficacy of various antiviral reagents against HBV cccDNA.
Main Methods:
- Development of an artificial recombinant HBV cccDNA (rcccDNA) system regulated by loxP-HBV genome and CRE expression.
- Screening of 379 antiviral reagents using the established rcccDNA system.
- Validation of identified compounds in an HBV infection model.
Main Results:
- Several compounds, including danoprevir, L- and D-cycloserine, phenytoin sodium, amantadine, and germacrone, demonstrated a reduction in cccDNA levels.
- D-cycloserine notably decreased HBV antigen secretion and induced cccDNA degradation in the HBV infection system.
- The screening system successfully identified potential therapeutic candidates targeting cccDNA.
Conclusions:
- The developed drug screening system is effective for identifying compounds that reduce HBV cccDNA.
- D-cycloserine shows significant potential as a therapeutic agent for targeting HBV cccDNA and reducing viral antigens.
- This platform facilitates the development of novel drugs aimed at cccDNA eradication for treating chronic Hepatitis B.
