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Published on: December 21, 2019
Triterpenoids CDDO and CDDO-EA Inhibit the Replication of Hepatitis B Virus by Modulating Nucleocapsid Assembly
Qiang Gao1, Ge Yang1, Ya Wang1
1CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Technology and Application for Anti-Infective New Drugs Research and Development, NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Two synthetic triterpenoids, CDDO and CDDO-EA, inhibit hepatitis B virus (HBV) DNA replication by disrupting HBV capsid assembly. These compounds show potential as novel antiviral agents for chronic HBV infection.
Area of Science:
- Hepatology
- Virology
- Medicinal Chemistry
Background:
- Chronic hepatitis B virus (HBV) infection is a significant global health issue with limited curative treatments.
- Synthetic triterpenoids offer potential therapeutic benefits for liver diseases.
Purpose of the Study:
- To identify novel antiviral agents against HBV.
- To investigate the mechanism of action of synthetic triterpenoids CDDO and CDDO-EA against HBV.
Main Methods:
- Screening of synthetic triterpenoids for HBV inhibition.
- Analysis of HBV DNA replication, pgRNA levels, and core protein expression.
- Particle gel assay, Western blot, CETSA, SPR, and molecular docking.
- Assessment of synergistic effects with lamivudine.
Main Results:
- CDDO and CDDO-EA significantly inhibited HBV DNA replication.
- These compounds reduced extracellular and intracellular pgRNA without affecting total pgRNA or core protein levels.
- CDDO and CDDO-EA promoted empty HBV capsid formation and modulated core protein phosphorylation.
- Direct binding of CDDO and CDDO-EA to HBV core protein dimer-dimer interfaces was demonstrated.
- CDDO-EA exhibited synergistic effects with lamivudine in reducing HBV DNA.
Conclusions:
- CDDO and CDDO-EA function as novel HBV capsid assembly modulators.
- These triterpenoids represent promising lead compounds for developing new anti-HBV therapies.
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