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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
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Antiviral activity of stachyflin on influenza A viruses of different hemagglutinin subtypes
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| Title: | Antiviral activity of stachyflin on influenza A viruses of different hemagglutinin subtypes |
| Authors: | Motohashi, Yurie Browse this author | | Igarashi, Manabu Browse this author →KAKEN DB | | Okamatsu, Masatoshi Browse this author →KAKEN DB | | Noshi, Takeshi Browse this author | | Sakoda, Yoshihiro Browse this author →KAKEN DB | | Yamamoto, Naoki Browse this author | | Ito, Kimihito Browse this author →KAKEN DB | | Yoshida, Ryu Browse this author | | Kida, Hiroshi Browse this author →KAKEN DB |
| Keywords: | Stachyflin | | Anti-influenza drug | | HA inhibitor | | Docking model |
| Issue Date: | 16-Apr-2013 |
| Publisher: | BioMed Central |
| Journal Title: | Virology Journal |
| Volume: | 10 |
| Start Page: | 118 |
| Publisher DOI: | 10.1186/1743-422X-10-118 |
| Abstract: | Background: The hemagglutinin (HA) of influenza viruses is a possible target for antiviral drugs because of its key roles in the initiation of infection. Although it was found that a natural compound, Stachyflin, inhibited the growth of H1 and H2 but not H3 influenza viruses in MDCK cells, inhibitory activity of the compound has not been assessed against H4-H16 influenza viruses and the precise mechanism of inhibition has not been clarified. Methods: Inhibitory activity of Stachyflin against H4-H16 influenza viruses, as well as H1-H3 viruses was examined in MDCK cells. To identify factors responsible for the susceptibility of the viruses to this compound, Stachyflin-resistant viruses were selected in MDCK cells and used for computer docking simulation. Results: It was found that in addition to antiviral activity of Stachyflin against influenza viruses of H1 and H2 subtypes, it inhibited replication of viruses of H5 and H6 subtypes, as well as A(H1N1)pdm09 virus in MDCK cells. Stachyflin also inhibited the virus growth in the lungs of mice infected with A/WSN/1933 (H1N1) and A/chicken/Ibaraki/1/2005 (H5N2). Substitution of amino acid residues was found on the HA2 subunit of Stachyflin-resistant viruses. Docking simulation indicated that D37, K51, T107, and K121 are responsible for construction of the cavity for the binding of the compound. In addition, 3-dimensional structure of the cavity of the HA of Stachyflin-susceptible virus strains was different from that of insusceptible virus strains. Conclusion: Antiviral activity of Stachyflin was found against A(H1N1) pdm09, H5, and H6 viruses, and identified a potential binding pocket for Stachyflin on the HA. The present results should provide us with useful information for the development of HA inhibitors with more effective and broader spectrum. |
| Rights: | http://creativecommons.org/licenses/by/2.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/53181 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 喜田 宏
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