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Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3088-93. doi: 10.1073/pnas.0712380105. Epub 2008 Feb 19.

A virocidal amphipathic {alpha}-helical peptide that inhibits hepatitis C virus infection in vitro.

Author information

1
Departments of Molecular and Experimental Medicine, Chemistry, and Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

An amphipathic alpha-helical peptide (C5A) derived from the membrane anchor domain of the hepatitis C virus (HCV) NS5A protein is virocidal for HCV at submicromolar concentrations in vitro. C5A prevents de novo HCV infection and suppresses ongoing infection by inactivating both extra- and intracellular infectious particles, and it is nontoxic in vitro and in vivo at doses at least 100-fold higher than required for antiviral activity. Mutational analysis indicates that C5A's amphipathic alpha-helical structure is necessary but not sufficient for its virocidal activity, which depends on its amino acid composition but not its primary sequence or chirality. In addition to HCV, C5A inhibits infection by selected flaviviruses, paramyxoviruses, and HIV. These results suggest a model in which C5A destabilizes viral membranes based on their lipid composition, offering a unique therapeutic approach to HCV and other viral infections.

PMID:
18287023
PMCID:
PMC2268589
DOI:
10.1073/pnas.0712380105
[Indexed for MEDLINE]
Free PMC Article

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