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Chem Biol. 2011 Nov 23;18(11):1453-62. doi: 10.1016/j.chembiol.2011.08.017.

Self-assembling peptide nanotubes with antiviral activity against hepatitis C virus.

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Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.


Hepatitis C virus (HCV) infects chronically 3% of the world population and the current therapy against this pathogen is only partially effective. With the aim of developing novel antiviral strategies against HCV, we screened a D,L-α-peptide library using an unbiased methodology based on a cell culture infection system for HCV. We found a family of highly active amphiphilic eight-residue cyclic D,L-α-peptides that specifically blocked entry of all tested HCV genotypes into target cells at a postbinding step without affecting infection by other enveloped RNA viruses. Structure-activity relationship studies indicate that antiviral activity was dependent on cyclic D,L-α-peptide self-assembly processes and that, although they possess a net neutral charge, they display a characteristic charge distribution. Our results indicate that supramolecular amphiphilic peptide structures constitute a class of highly selective HCV entry inhibitors.

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