title: Inhibition of PA endonuclease activity of influenza virus RNA polymerase by Kampo medicines.
abstract: To find a novel influenza inhibitor targeting the endonuclease activity of influenza A virus polymerase acidic protein (PA), which is essential for the acquisition of primers for viral mRNA transcription, seven Kampo extracts were tested in vitro for their ability to inhibit endonuclease activity of the recombinant PA protein that was expressed and purified from Escherichia coli. The Kampo medicines Kakkonto, Shosaikoto, Saikokeishito, Keishito, Maobushisaishinto, and Maoto, but not Chikujountanto, inhibited PA endonuclease activity in a dose-dependent manner. Our results indicate that Kampo medicines are good sources providing a structural lead for optimization of an influenza endonuclease inhibitor.
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University.
authors.forename: Riku
authors.initials: R
authors.lastname: Shirayama
authors.forename: Masaki
authors.initials: M
authors.lastname: Shoji
authors.forename: Nongluk
authors.initials: N
authors.lastname: Sriwilaijaroen
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hiramatsu
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuzuhara
mesh_terms: D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D009980:Influenza A virus / Q000201:enzymology; D020835:Medicine, Kampo; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; C057027:PB2 protein, Influenzavirus A; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase