2012 Fiscal Year Final Research Report
Screening of inhibitors of influenza A virus PA endonuclease
| Project/Area Number |
22590422
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Virology
|
|---|
| Research Institution | Tokushima Bunri University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Keywords | RNA ポリメラーゼ / インフルエンザ / エンドヌクレアーゼ / カテキン / サリドマ イド / フェネチルフェニルフサリミド / 天然物化合物 / 阻害剤 |
|---|
| Research Abstract |
The H1N1 influenza A virus of swine-origin caused pandemics throughout the world in2009 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 th
… More
e 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. Less
|
Research Products
(65 results)
-
-
-
-
[Journal Article] Anti-Influenza Activity of Marchantins, Macrocyclic Bisbibenzyls Contained in Liverworts.2011
Author(s)
Iwai Y, Murakami K, Gomi Y, Hashimoto T, Asakawa Y, Okuno Y, Ishikawa T, Hatakeyama D, Echigo N, Kuzuhara T.
-
Journal Title
PLoS ONE
Volume: 6(5)
Pages: e19825
DOI
-
-
-
-
-
[Journal Article] Anti-influenza Activity of Phenethylphenylphthalimide Analogs Derived from Thalidomide.2010
Author(s)
Iwai Y, Takahashi H, Hatakeyama D, Motoshima K, Ishikawa M, Sugita K, Hashimoto Y, Harada Y, Itamura S, Odagiri T, Tashiro M, Sei Y, Yamaguchi K, Kuzuhara T.
-
Journal Title
Bioorganic & Medicinal Chemistry
Volume: 18
Pages: 5379-5390
DOI
-
[Journal Article] Anti-influenza activity of C60 fullerene derivatives.
Author(s)
Shoji M., Takahashi E., Hatakeyama D., IwaiY.,MoritaY.,Shirayama R.,Echigo N., Kido H., Nakamura S., Mashino T., Okutani T., Kuzuhara T.
-
Journal Title
PLoS ONE
Volume: (in press)
DOI
-
[Journal Article] Identification and purification of resorcinol, an antioxidant specific to Awa-ban (pickled and anaerobically fermented) tea.
Author(s)
Hiasa M, Kurokawa M, Ohta K, Esumi T, Akita H, Niki K, Yagi Y, Echigo N, Hatakeyama D, Kuzuhara T.
-
Journal Title
Food Research International
Volume: (in press)
DOI
-
-
[Presentation] Fullerene derivativesによるインフルエンザPAサブユニットのエンドヌクレアーゼ活性及びウイルス感染阻害効果の検討2013
Author(s)
庄司正樹,畠山大,高橋悦久,森田悠香,奥谷武史,岩井佑磨,越後典子,木戸博,中村成夫,増野匡彦,葛原隆
Organizer
第133回日本薬学会年会
Place of Presentation
横浜
Year and Date
20130327-30
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] 大環状ビスビベンジル分子による抗インフルエンザ活性2011
Author(s)
畠山大,岩井佑磨,村上宏起,五味康行,奥谷武史,橋本敏弘,浅川義範,奥野良信,石川豊数,越後典子,葛原隆
Organizer
第50回日本薬学会・中国四国支部学術大会
Place of Presentation
高松市
Year and Date
20111112-13
-
[Presentation] コケ植物由来の大環状ビスビベンジル分子による抗インフルエンザウイルス活性2011
Author(s)
畠山大,岩井佑磨,村上宏起,五味康行,奥谷武史,橋本敏弘,浅川義範,奥野良信,石川豊数,越後典子,葛原隆
Organizer
第49回日本生物物理学会年会
Place of Presentation
兵庫県立大学
Year and Date
20110916-18
-
[Presentation] コケ植物の環状ビスビベンジル分子マルカンチンによる抗インフルエンザウイルス活性2011
Author(s)
畠山大,岩井佑磨,村上宏起,五味康行,奥谷武史,橋本敏弘,浅川義範,奥野良信,石川豊数,越後典子,葛原隆
Organizer
第3回日本生物物理学会中国四国支部会
Place of Presentation
広島大学
Year and Date
20110514-15
-
-
[Presentation] サリドマイド由来誘導体による抗インフルエンザ活性2011
Author(s)
岩井佑磨,高橋仁,畠山大,本島和典,石川稔,杉田和幸,橋本祐一,原田勇一,板村繁之,小田切孝人,田代眞人,清悦久,山口健太郎,葛原隆
Organizer
日本薬学会第131年会
Place of Presentation
静岡
Year and Date
20110300
-
-
-
-
-
-
-
-
-
-
-
[Presentation] サリドマイド由来誘導体による抗インフルエンザウイルス活性の構造学的および生化学的解析2010
Author(s)
畠山大,岩井佑磨,高橋仁,本島和典,石川稔,杉田和幸,橋本祐一,原田勇一,板村繁之,小田切孝人,田代眞人,清悦久,山口健太郎,葛原隆
Organizer
第49回日本薬学会中国四国支部学術大会
Place of Presentation
鳥取県米子市
Year and Date
20101106-07
-
[Presentation] サリドマイド・アナログの抗インフルエンザウイルス活性2010
Author(s)
畠山大,岩井佑磨,高橋仁,本島和典,石川稔,杉田和幸,橋本祐一,原田勇一,板村繁之,小田切孝人,田代眞人,清悦久,山口健太郎,葛原隆
Organizer
日本生物物理学会第48回年会
Place of Presentation
東北大学
Year and Date
20100920-22
-
-
-
-
[Presentation] Thalidomide analogs as a new strategy against influenza A2010
Author(s)
Hatakeyama D, Iwai Y, Takahashi H, Motoshima K, Ishikawa M, Sugita K, Hashimoto Y, Harada Y, Itamura S, Odagiri T, Tashiro M, Sei Y, Yamaguchi K, Kuzuhara T
Organizer
Cell Symposia Influenza: Translating basic insights
Place of Presentation
Washington D.C., USA.
Year and Date
2010-12-24
-
[Presentation] サリドマイド由来誘導体の抗インフルエンザ活性2010
Author(s)
畠山大,岩井佑磨,高橋仁,本島和典,石川稔,杉田和幸,橋本祐一,原田勇一,板村繁之,小田切孝人,田代眞人,清悦久,山口健太郎,葛原隆
Organizer
日本生物物理学会第2回中国四国支部大会
Place of Presentation
松山大学
Year and Date
2010-05-08
-
-
-
