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: Wei Hong, Yange Lang, Tian Li, Zhengyang Zeng, Yu Song, Yingliang Wu, Wenxin Li, Zhijian Cao
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 38 Pg. 23254-63 (Sep 18 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 26251517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Antiviral Agents
• Ion Channels
• Peptides
• Viral Proteins
• p7 protein, Hepatitis C virus

Topics

• Antiviral Agents (chemistry, pharmacology)
• HeLa Cells
• Hepacivirus (genetics, metabolism)
• Hepatitis C (drug therapy, genetics, metabolism)
• Humans
• Ion Channels (chemistry)
• Peptides (chemistry, pharmacology)
• Viral Proteins (chemistry)
• Virus Release (drug effects)