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

被引:12
作者
Matusevich, O. V. [1 ]
Egorov, V. V. [2 ,4 ]
Gluzdikov, I. A. [1 ]
Titov, M. I. [1 ]
Zarubaev, V. V. [2 ]
Shtro, A. A. [2 ]
Slita, A. V. [2 ]
Dukov, M. I. [2 ]
Shurygina, A. -P. S. [2 ]
Smirnova, T. D. [2 ]
Kudryavtsev, I. V. [3 ,5 ]
Vasin, A. V. [2 ,6 ]
Kiselev, O. I. [2 ]
机构
[1] St Petersburg State Univ, Fac Chem, St Petersburg 198504, Russia
[2] Res Inst Influenza, Dept Mol Virol, St Petersburg 197376, Russia
[3] RAMS, NWB, IEM, St Petersburg 197376, Russia
[4] Petersburg Nucl Phys Inst, NRC KI, Gatchina 188300, Russia
[5] Far East Fed Univ, Vladivostok 690950, Russia
[6] State Polytech Univ, St Petersburg 195251, Russia
关键词
Influenza A; Antiviral peptides; Influenza A polymerase; PB1; VIRUS POLYMERASE;
D O I
10.1016/j.antiviral.2014.10.015
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 (HI NI) 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. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:4 / 10
页数:7
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