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

• Peptides corresponding to portions of the amino acid sequence of the PB1 protein was selected and synthesized.
• Terminal modifications (acetylation and amidation) were shown to increase the activity of the peptides significantly.
• The most active peptide is able to cross the cell membrane.
• Mechanism of its action did not involve the inactivation of the virus outside of the cell.
• Inhibition of influenza virus by the peptide took place during the early stages of viral reproduction.

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.