Antiviral peptide nanocomplexes as a potential therapeutic modality for HIV/HCV co-infection

Jinjin Zhang, Andrea Mulvenon, Edward Makarov, Jill Wagoner, Jaclyn Knibbe, Jong Oh Kim, Natalia A Osna, Tatiana K Bronich, Larisa Y Poluektova

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

It is estimated that 4 to 5 million people are currently co-infected with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). HIV/HCV co-infection is associated with unique health risks including increased hepatotoxicity of antiretrovirals, accelerated progression of HCV and liver diseases. The standard interferon-based therapy is effective only in about 50% of patients and often is associated with autoimmune and neuro-psychiatric complications. The treatment of co-infection (HIV/HCV) requires new strategic approaches. To this end, the formulations of an amphiphatic α-helical peptide, a positively charged analog of C5A peptide derived from the HCV NS5A protein, with a reported virocidal activity were prepared by electrostatic coupling with anionic poly(amino acid)-based block copolymers. The self-assembled antiviral peptide nanocomplexes (APN) were ca. 35 nm in size, stable at physiological pH and ionic strength, and retained in vitro antiviral activity against HCV and HIV. Moreover, incorporation of the peptide into APN attenuated its cytotoxicity associated with the positive charge. In vivo APN were able to decrease the viral load in mice transplanted with human lymphocytes and HIV-1-infected. Overall, these findings indicate the potential of these formulations for stabilization and delivery of antiviral peptides while maintaining their functional activity.

Original languageEnglish (US)
Pages (from-to)3846-3857
Number of pages12
JournalBiomaterials
Volume34
Issue number15
DOIs
StatePublished - May 1 2013

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Keywords

  • Amphiphatic α-helical peptide
  • Anionic poly (amino acid)-based block copolymer
  • HCV
  • HIV-1
  • Human hepatoma cell line Huh7.5
  • Macrophages

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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