Synthesis and antiviral activity of PB1 component of the influenza A RNA polymerase peptide fragments

Antiviral Res. 2015 Jan;113:4-10. doi: 10.1016/j.antiviral.2014.10.015. Epub 2014 Nov 12.

Abstract

This study is devoted to the antiviral activity of peptide fragments from the PB1 protein - a component of the influenza A RNA polymerase. The antiviral activity of the peptides synthesized was studied in MDCK cell cultures against the pandemic influenza strain A/California/07/2009 (H1N1) pdm09. We found that peptide fragments 6-13, 6-14, 26-30, 395-400, and 531-540 of the PB1 protein were capable of suppressing viral replication in cell culture. Terminal modifications i.e. N-acetylation and C-amidation increased the antiviral properties of the peptides significantly. Peptide PB1 (6-14) with both termini modified showed maximum antiviral activity, its inhibitory activity manifesting itself during the early stages of viral replication. It was also shown that the fluorescent-labeled analog of this peptide was able to penetrate into the cell. The broad range of virus-inhibiting activity of PB1 (6-14) peptide was confirmed using a panel of influenza A viruses of H1, H3 and H5 subtypes including those resistant to oseltamivir, the leading drug in anti-influenza therapy. Thus, short peptide fragments of the PB1 protein could serve as leads for future development of influenza prevention and/or treatment agents.

Keywords: Antiviral peptides; Influenza A; Influenza A polymerase; PB1.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology
  • Dogs
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / physiology
  • Influenza A virus / drug effects*
  • Influenza A virus / physiology
  • Madin Darby Canine Kidney Cells
  • Molecular Sequence Data
  • Oseltamivir / pharmacology
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • RNA Replicase / chemistry*
  • Viral Proteins / chemistry*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Peptide Fragments
  • Viral Proteins
  • influenza virus polymerase basic protein 1
  • Oseltamivir
  • RNA Replicase