Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts.
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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2011-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3098833?pdf=render |
_version_ | 1811325347436691456 |
---|---|
author | Yuma Iwai Kouki Murakami Yasuyuki Gomi Toshihiro Hashimoto Yoshinori Asakawa Yoshinobu Okuno Toyokazu Ishikawa Dai Hatakeyama Noriko Echigo Takashi Kuzuhara |
author_facet | Yuma Iwai Kouki Murakami Yasuyuki Gomi Toshihiro Hashimoto Yoshinori Asakawa Yoshinobu Okuno Toyokazu Ishikawa Dai Hatakeyama Noriko Echigo Takashi Kuzuhara |
author_sort | Yuma Iwai |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-13T14:31:41Z |
format | Article |
id | doaj.art-4efb62e14d7440009a94ee1f46f24418 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-13T14:31:41Z |
publishDate | 2011-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-4efb62e14d7440009a94ee1f46f244182022-12-22T02:43:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e1982510.1371/journal.pone.0019825Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts.Yuma IwaiKouki MurakamiYasuyuki GomiToshihiro HashimotoYoshinori AsakawaYoshinobu OkunoToyokazu IshikawaDai HatakeyamaNoriko EchigoTakashi KuzuharaThe 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.http://europepmc.org/articles/PMC3098833?pdf=render |
spellingShingle | Yuma Iwai Kouki Murakami Yasuyuki Gomi Toshihiro Hashimoto Yoshinori Asakawa Yoshinobu Okuno Toyokazu Ishikawa Dai Hatakeyama Noriko Echigo Takashi Kuzuhara Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts. PLoS ONE |
title | Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts. |
title_full | Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts. |
title_fullStr | Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts. |
title_full_unstemmed | Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts. |
title_short | Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts. |
title_sort | anti influenza activity of marchantins macrocyclic bisbibenzyls contained in liverworts |
url | http://europepmc.org/articles/PMC3098833?pdf=render |
work_keys_str_mv | AT yumaiwai antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts AT koukimurakami antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts AT yasuyukigomi antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts AT toshihirohashimoto antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts AT yoshinoriasakawa antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts AT yoshinobuokuno antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts AT toyokazuishikawa antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts AT daihatakeyama antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts AT norikoechigo antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts AT takashikuzuhara antiinfluenzaactivityofmarchantinsmacrocyclicbisbibenzylscontainedinliverworts |