title: Efficient Inhibition of Hepatitis B Virus Infection by a preS1-binding Peptide.
abstract: Entry inhibitors are promising novel antivirals against hepatitis B virus (HBV) infection. The existing potential entry inhibitors have targeted the cellular receptor(s). In this study, we aim to develop the first entry inhibitor that inhibits HBV infection via targeting viral particles. The preS1 segment of the large envelope glycoprotein of HBV is essential for virion attachment and infection. Previously, we obtained a preS1-binding short peptide B10 by screening a phage display peptide library using the N-terminal half of preS1 (residues 1 to 60, genotype C). We report here that by means of concatenation of B10, we identified a quadruple concatemer 4B10 that displayed a markedly increased preS1-binding activity. The main binding site of 4B10 in preS1 was mapped to the receptor binding enhancing region. 4B10 blocked HBV attachment to hepatic cells and inhibited HBV infection of primary human and tupaia hepatocytes at low nanomolar concentrations. The 4B10-mediated inhibition of HBV infection is specific as it did not inhibit the infection of vesicular stomatitis virus glycoprotein pseudotyped lentivirus or human immunodeficiency virus type 1. Moreover, 4B10 showed no binding activity to hepatic cells. In conclusion, we have identified 4B10 as a promising candidate for a novel class of HBV entry inhibitors.
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE &MOH), Institute of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Virology, Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071,China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE &MOH), Institute of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: He
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE &MOH), Institute of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Weiya
authors.initials: W
authors.lastname: Bai
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE &MOH), Institute of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Tao
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Ruijing Hospital, Medical School, Shanghai Jiaotong University, 200025, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE &MOH), Institute of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE &MOH), Institute of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Junqi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071,China.|Biomedical Center, Hubei University of Technology, Wuhan, 430068, China.
authors.forename: Kanghong
authors.initials: K
authors.lastname: Hu
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE &MOH), Institute of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D002478:Cells, Cultured; D005434:Flow Cytometry; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry*; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011498:Protein Precursors / Q000737:chemistry*; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen