title: Antiviral peptide nanocomplexes as a potential therapeutic modality for HIV/HCV co-infection.
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.
authors: Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE 68198-5830, USA.
authors: Jinjin
authors: J
authors: Zhang
authors: Andrea
authors: A
authors: Mulvenon
authors: Edward
authors: E
authors: Makarov
authors: Jill
authors: J
authors: Wagoner
authors: Jaclyn
authors: J
authors: Knibbe
authors: Jong Oh
authors: JO
authors: Kim
authors: Natalia
authors: N
authors: Osna
authors: Tatiana K
authors: TK
authors: Bronich
authors: Larisa Y
authors: LY
authors: Poluektova
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002942:Circular Dichroism; D060085:Coinfection / Q000188:drug therapy* / Q000821:virology; D004705:Endocytosis / Q000187:drug effects; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D059748:Proteolysis / Q000187:drug effects; D014357:Trypsin / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D014357:Trypsin
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