Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5821974 | Antiviral Research | 2016 | 9 Pages |
Abstract
During the hepatitis B virus (HBV) life cycle, nucleocapsid assembly is essential for HBV replication. Both RNA reverse transcription and DNA replication occur within the HBV nucleocapsid. HBV nucleocapsid is consisted of core protein (HBcAg), whose carboxy-terminal domain (CTD) contains an Arg-rich domain (ARD). The ARD of HBcAg does contribute to the encapsidation of pregenomic RNA (pgRNA). Previously, we reported a small-molecule, NZ-4, which dramatically reduced the HBV DNA level in an in vitro cell setting. Here, we explore the possible mechanisms by which NZ-4 inhibits HBV function. As an HBV inhibitor, NZ-4 leads to the formation of genome-free capsids, including a new population of capsid that runs faster on agarose gels. NZ-4's activity was dependent on the presence of the ARD I, containing at least one positively charged amino acid. NZ-4 might provide a new option for further development of HBV therapeutics for the treatment of chronic hepatitis B.
Keywords
HBcAgssDNApgRNArelaxed circular DNACTDqRT-PCRrcDNA3TCARDSingle-stranded DNApregenomic RNAcarboxy-terminal domainDigoxinDIGLamivudinewild-typeHBVquantitative real-time reverse transcriptase polymerase chain reactionhepatitis B virusCore proteinpolPolymerasehigh-performance liquid chromatographyHPLCHAp
Related Topics
Life Sciences
Immunology and Microbiology
Virology
Authors
Li Yang, Ya-Juan Wang, Hai-Jun Chen, Li-Ping Shi, Xian-Kun Tong, Yang-Ming Zhang, Gui-Feng Wang, Wen-Long Wang, Chun-Lan Feng, Pei-Lan He, Yi-Bin Xu, Meng-Ji Lu, Wei Tang, Fa-Jun Nan, Jian-Ping Zuo,