title: Inhibition of hepatitis B virus replication by Bay 41-4109 and its association with nucleocapsid disassembly.
abstract: 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.
authors.affiliation: Hepatology Institute, People's Hospital, Peking University, Beijing, China.
authors.forename: Guo-Yi
authors.initials: GY
authors.lastname: Wu
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Zheng
authors.forename: Chang-Cheng
authors.initials: CC
authors.lastname: Yin
authors.forename: Dong
authors.initials: D
authors.lastname: Jiang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong-Song
authors.initials: HS
authors.lastname: Chen
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D004279:DNA, Viral / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006512:Hepatitis B Core Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019251:Nucleocapsid / Q000187:drug effects* / Q000502:physiology; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; C464059:BAY 41-4109; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D011725:Pyridines; D011743:Pyrimidines; D014764:Viral Proteins