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Inhibition of Hepatitis B Virus Replication by Bay 41-4109 and Its Association with Nucleocapsid Disassembly

2008; Taylor & Francis; Volume: 20; Issue: 4 Linguagem: Inglês

10.1179/joc.2008.20.4.458

1973-9478

Guoyi Wu, Xiaojing Zheng, Changcheng Yin, Dong Jiang, Ling Zhu, Yan Liu, Lai Wei, Yu Wang, Hongsong Chen,

Viral gastroenteritis research and epidemiology

AbstractAbstractThe 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 ex-pressed 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.Keywords: Hepatitis BBay 41-4109HBV DNAcore proteinantiviral effects