title: Effect of a hepatitis B virus inhibitor, NZ-4, on capsid formation.
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.
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Chinese National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Shi
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xian-Kun
authors.initials: XK
authors.lastname: Tong
authors.affiliation: Chinese National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yang-Ming
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Gui-Feng
authors.initials: GF
authors.lastname: Wang
authors.affiliation: Chinese National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chun-Lan
authors.initials: CL
authors.lastname: Feng
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Pei-Lan
authors.initials: PL
authors.lastname: He
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Xu
authors.affiliation: Tongji Hospital of Tongji Medical College, Wuhan, China.
authors.forename: Meng-Ji
authors.initials: MJ
authors.lastname: Lu
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Chinese National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: fjnan@mail.shcnc.ac.cn.
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Nan
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: jpzuo@mail.shcnc.ac.cn.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zuo
mesh_terms: D000595:Amino Acid Sequence; D002213:Capsid / Q000187:drug effects* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D016679:Genome, Viral; D056945:Hep G2 Cells; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D013844:Thiazoles; C000595585:isothiafludine; D004722:Endoribonucleases; D010749:Phosphoprotein Phosphatases; C097081:PPP1R8 protein, human
keywords: Anti-hepatitis B virus compound; Arg-rich domain I; Capsid formation; Faster-migrating capsid; pgRNA packaging