| 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
|
| リソース情報 |
| 遺伝子材料 |
pBMSA-PA (RDB01971) |
