Inhibition of hepatitis B virus replication by Bay 41-4109 and its association with nucleocapsid disassembly
| Autor: | Hong-Song Chen, Guo-Yi Wu, Lai Wei, Dong Jiang, Xiao-Jing Zheng, Yan Liu, Ling Zhu, Yu Wang, Chang-Cheng Yin |
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| Předmět: |
Hepatitis B virus
Pyridines Hepatitis B virus DNA polymerase Blotting Western Fluorescent Antibody Technique Biology Virus Replication medicine.disease_cause Antiviral Agents Polymerase Chain Reaction Virus Cell Line Viral Proteins Orthohepadnavirus medicine Humans Pharmacology (medical) Nucleocapsid Pharmacology Dose-Response Relationship Drug virus diseases Hepatitis B biology.organism_classification medicine.disease Hepatitis B Core Antigens Virology digestive system diseases HBcAg Pyrimidines Infectious Diseases Oncology Capsid Hepadnaviridae DNA Viral |
| Zdroj: | Scopus-Elsevier |
| Popis: | The authors investigate the effects and mechanisms of the anti-hepatitis B virus (HBV) agent Bay 41-4109. HepG2.2.15 cells were used to investigate the antiviral effects of Bay 41-4109 by using real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence. The C terminally truncated core protein was expressed and purified. Changes in hepatitis B capsid formation were assayed by dynamic light scattering and transmission electronic microscopy. Bay 41-4109 was found to be a highly selective and potent inhibitor of hepatitis B virus replication in HepG2.2.15 cells. This compound was equally effective at inhibiting HBV DNA release and the cytoplasmic HBcAg level, with 50% inhibitory concentrations of 32.6 and 132 nM, respectively. HBV DNA and HBcAg were inhibited in a dose-dependent manner, indicating that the anti-HBV mechanisms are associated with and dependent on the rate of HBcAg inhibition. Our results indicate that Bay 41-4109 treatment disassembled the core capsids and separated them into monomers or dimers, the form in which they could be further degraded into peptides. The core protein assembled in a misdirected manner cannot function effectively. Our results suggest that, based on its particular activities, Bay 41-4109 is a promising anti-HBV candidate. |
| Databáze: | OpenAIRE |
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