Open AccessA virocidal amphipathic α-helical peptide that inhibits hepatitis C virus infection in vitro
Author(s) -
Guofeng Cheng,
Ana Montero,
Pablo Gastaminza,
Christina Whitten-Bauer,
Stefan Wieland,
Masanori Isogawa,
Brenda L. Fredericksen,
Suganya Selvarajah,
Philippe Gallay,
Mojtaba Ghadiri,
Francis V. Chisari
Publication year - 2008
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0712380105
Subject(s) - in vitro , virology , peptide , ns5a , hepatitis c virus , in vivo , biology , amphiphile , virus , peptide sequence , chemistry , biochemistry , hepacivirus , microbiology and biotechnology , organic chemistry , gene , copolymer , polymer
An amphipathic α-helical peptide (C5A) derived from the membrane anchor domain of the hepatitis C virus (HCV) NS5A protein is virocidal for HCV at submicromolar concentrationsin vitro . C5A preventsde novo HCV infection and suppresses ongoing infection by inactivating both extra- and intracellular infectious particles, and it is nontoxicin vitro andin vivo at doses at least 100-fold higher than required for antiviral activity. Mutational analysis indicates that C5A's amphipathic α-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.