A virocidal arnphipathic α-helical peptide that inhibits hepatitis C virus infection in vitro

被引：122

作者：

Cheng, Guofeng ^{[1
]}

Montero, Ana ^{[2
]}

Gastaminza, Pablo ^{[1
]}

Whitten-Bauer, Christina ^{[1
]}

Wieland, Stefan F. ^{[1
]}

Isogawa, Masanori ^{[1
]}

Fredericksen, Brenda ^{[4
]}

Selvarajah, Suganya ^{[3
]}

Gallay, Philippe A. ^{[3
]}

Ghadiri, M. Reza ^{[2
]}

Chisari, Francis V. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA

[4] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 08期

关键词：

HCV; amphipathic peptide; antiviral peptide; NS5A; HIV;

D O I：

10.1073/pnas.0712380105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

An amphipathic a-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 a-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.

引用

页码：3088 / 3093

页数：6

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