title: A p7 Ion Channel-derived Peptide Inhibits Hepatitis C Virus Infection in Vitro.
abstract: Viral infection is an early stage of its life cycle and represents a promising target for antiviral drug development. Here we designed and characterized three peptide inhibitors of hepatitis C virus (HCV) infection based on the structural features of the membrane-associated p7 polypeptide of HCV. The three peptides exhibited low toxicity and high stability while potently inhibiting initial HCV infection and suppressed established HCV infection at non-cytotoxic concentrations in vitro. The most efficient peptide (designated H2-3), which is derived from the H2 helical region of HCV p7 ion channel, inhibited HCV infection by inactivating both intracellular and extracellular viral particles. The H2-3 peptide inactivated free HCV with an EC50 (50% effective concentration) of 82.11 nm, which is >1000-fold lower than the CC50 (50% cytotoxic concentration) of Huh7.5.1 cells. H2-3 peptide also bound to cell membrane and protected host cells from viral infection. The peptide H2-3 did not alter the normal electrophysiological profile of the p7 ion channel or block viral release from Huh7.5.1 cells. Our work highlights a new anti-viral peptide design strategy based on ion channel, giving the possibility that ion channels are potential resources to generate antiviral peptides.
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Yange
authors.initials: Y
authors.lastname: Lang
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Li
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Zhengyang
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.affiliation: From the State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China zjcao@whu.edu.cn.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cao
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D014764:Viral Proteins / Q000737:chemistry*; D057074:Virus Release / Q000187:drug effects*; D000086082:Viroporin Proteins
chemical_list: D000998:Antiviral Agents; D007473:Ion Channels; D010455:Peptides; D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins
keywords: antiviral agent; hepatitis C virus (HCV); ion channel; peptides; viral protein; virus entry