論文 - 詳細
| RRC ID | 12232 |
|---|---|
| 著者 | Iwai Y, Murakami K, Gomi Y, Hashimoto T, Asakawa Y, Okuno Y, Ishikawa T, Hatakeyama D, Echigo N, Kuzuhara T. |
| タイトル | Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts. |
| ジャーナル | PLoS One |
| Abstract |
The H1N1 influenza A virus of swine-origin caused pandemics throughout the world in 2009 and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. The threat of influenza A thus remains a serious global health issue and novel drugs that target these viruses are highly desirable. Influenza A possesses an endonuclease within its RNA polymerase which comprises PA, PB1 and PB2 subunits. To identify potential new anti-influenza compounds in our current study, we screened 33 different types of phytochemicals using a PA endonuclease inhibition assay in vitro and an anti-influenza A virus assay. The marchantins are macrocyclic bisbibenzyls found in liverworts, and plagiochin A and perrottetin F are marchantin-related phytochemicals. We found from our screen that marchantin A, B, E, plagiochin A and perrottetin F inhibit influenza PA endonuclease activity in vitro. These compounds have a 3,4-dihydroxyphenethyl group in common, indicating the importance of this moiety for the inhibition of PA endonuclease. Docking simulations of marchantin E with PA endonuclease suggest a putative "fitting and chelating model" as the mechanism underlying PA endonuclease inhibition. The docking amino acids are well conserved between influenza A and B. In a cultured cell system, marchantin E was further found to inhibit the growth of both H3N2 and H1N1 influenza A viruses, and marchantin A, E and perrotein F showed inhibitory properties towards the growth of influenza B. These marchantins also decreased the viral infectivity titer, with marchantin E showing the strongest activity in this assay. We additionally identified a chemical group that is conserved among different anti-influenza chemicals including marchantins, green tea catechins and dihydroxy phenethylphenylphthalimides. Our present results indicate that marchantins are candidate anti-influenza drugs and demonstrate the utility of the PA endonuclease assay in the screening of phytochemicals for anti-influenza characteristics. |
| 巻・号 | 6(5) |
| ページ | e19825 |
| 公開日 | 2011-1-1 |
| DOI | 10.1371/journal.pone.0019825 |
| PII | PONE-D-10-05816 |
| PMID | 21625478 |
| PMC | PMC3098833 |
| MeSH | Animals Antiviral Agents / pharmacology* Cells, Cultured Computer Simulation Dogs Endonucleases / metabolism Hepatophyta / chemistry* Influenza A Virus, H1N1 Subtype / drug effects* Influenza A Virus, H3N2 Subtype / drug effects* Kidney / cytology Kidney / drug effects Kidney / virology Macrocyclic Compounds / pharmacology* Orthomyxoviridae Infections / drug therapy* Phytotherapy* |
| IF | 2.74 |
| 引用数 | 52 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pBMSA-PA (RDB01971) |