title: A human claudin-1-derived peptide inhibits hepatitis C virus entry.
abstract: Hepatitis C virus (HCV) entry is a complicated process that requires multiple host factors, such as CD81, scavenger receptor BI, claudin-1 (CLDN1), and occludin. The interaction of virus and cellular entry factors represents a promising target for novel anti-HCV drug development. In this study, we sought to identify peptide inhibitors for HCV entry by screening a library of overlapping peptides covering the four above-mentioned entry factors. An 18-amino acid peptide (designated as CL58) that was derived from the CLDN1 intracellular and first transmembrane region inhibited both de novo and established HCV infection in vitro. Unlike previously reported peptides corresponding to CLDN1 extracellular loops, CL58 did not alter the normal distribution of CLDN1 and was not cytotoxic in vitro at concentrations nearly 100-fold higher than the effective antiviral dose. The inhibitory effect of CL58 appeared to occur at a late step during viral entry, presumably after initial binding. Finally, overexpressed CL58 was able to interact with HCV envelope proteins.
  
  
  CONCLUSIONS
  We identified a novel CLDN1-derived peptide that inhibits HCV entry at a postbinding step. The findings expand our knowledge of the roles that CLDN1 play in HCV entry and highlight the potential for developing a new class of inhibitors targeting the viral entry process.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Youhui
authors.initials: Y
authors.lastname: Si
authors.forename: Shufeng
authors.initials: S
authors.lastname: Liu
authors.forename: Xiuying
authors.initials: X
authors.lastname: Liu
authors.forename: Jana L
authors.initials: JL
authors.lastname: Jacobs
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Niu
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
authors.forename: Tianyi
authors.initials: T
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D062445:Claudin-1; D015195:Drug Design; D006023:Glycoproteins / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006526:Hepatitis C / Q000378:metabolism / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D008565:Membrane Proteins / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C568108:CLDN1 protein, human; D062445:Claudin-1; D006023:Glycoproteins; D008565:Membrane Proteins; D010455:Peptides; D014764:Viral Proteins