title: Synthesis and antiviral activity of PB1 component of the influenza A RNA polymerase peptide fragments.
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.
authors.affiliation: Saint Petersburg State University, Faculty of Chemistry, 26, Universitetskii pr., Petrodvorets, St. Petersburg 198504, Russia.
authors.forename: O V
authors.initials: OV
authors.lastname: Matusevich
authors.affiliation: Research Institute of Influenza, Molecular Virology Department, 15/17, Prof. Popova str., St. Petersburg 197376, Russia; Petersburg Nuclear Physics Institute, NRC KI, Orlova roscha, Gatchina 188300, Russia. Electronic address: toizeg@gmail.com.
authors.forename: V V
authors.initials: VV
authors.lastname: Egorov
authors.affiliation: Saint Petersburg State University, Faculty of Chemistry, 26, Universitetskii pr., Petrodvorets, St. Petersburg 198504, Russia.
authors.forename: I A
authors.initials: IA
authors.lastname: Gluzdikov
authors.affiliation: Saint Petersburg State University, Faculty of Chemistry, 26, Universitetskii pr., Petrodvorets, St. Petersburg 198504, Russia.
authors.forename: M I
authors.initials: MI
authors.lastname: Titov
authors.affiliation: Research Institute of Influenza, Molecular Virology Department, 15/17, Prof. Popova str., St. Petersburg 197376, Russia.
authors.forename: V V
authors.initials: VV
authors.lastname: Zarubaev
authors.affiliation: Research Institute of Influenza, Molecular Virology Department, 15/17, Prof. Popova str., St. Petersburg 197376, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Shtro
authors.affiliation: Research Institute of Influenza, Molecular Virology Department, 15/17, Prof. Popova str., St. Petersburg 197376, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Slita
authors.affiliation: Research Institute of Influenza, Molecular Virology Department, 15/17, Prof. Popova str., St. Petersburg 197376, Russia.
authors.forename: M I
authors.initials: MI
authors.lastname: Dukov
authors.affiliation: Research Institute of Influenza, Molecular Virology Department, 15/17, Prof. Popova str., St. Petersburg 197376, Russia.
authors.forename: A-P S
authors.initials: AP
authors.lastname: Shurygina
authors.affiliation: Research Institute of Influenza, Molecular Virology Department, 15/17, Prof. Popova str., St. Petersburg 197376, Russia.
authors.forename: T D
authors.initials: TD
authors.lastname: Smirnova
authors.affiliation: Institute of Experimental Medicine of the North-West Branch of the Russian Academy of Medical Sciences (IEM NWB RAMS), 12, Akad. Pavlova str., St. Petersburg 197376, Russia; Far East Federal University, 8, Suhanova str., Vladivostok 690950, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Kudryavtsev
authors.affiliation: Research Institute of Influenza, Molecular Virology Department, 15/17, Prof. Popova str., St. Petersburg 197376, Russia; State Polytechnical University, 29, Polytecnicheskaya str., St. Petersburg 195251, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Vasin
authors.affiliation: Research Institute of Influenza, Molecular Virology Department, 15/17, Prof. Popova str., St. Petersburg 197376, Russia.
authors.forename: O I
authors.initials: OI
authors.lastname: Kiselev
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004285:Dogs; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D061985:Madin Darby Canine Kidney Cells; D008969:Molecular Sequence Data; D053139:Oseltamivir / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D010446:Peptide Fragments; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; D053139:Oseltamivir; D012324:RNA-Dependent RNA Polymerase
keywords: Antiviral peptides; Influenza A; Influenza A polymerase; PB1