title: Anti-influenza activity of c60 fullerene derivatives.
abstract: The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains a serious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymerase consists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity. Fullerene (C60) is a unique carbon molecule that forms a sphere. To identify potential new anti-influenza compounds, we screened 12 fullerene derivatives using an in vitro PA endonuclease inhibition assay. We identified 8 fullerene derivatives that inhibited the endonuclease activity of the PA N-terminal domain or full-length PA protein in vitro. We also performed in silico docking simulation analysis of the C60 fullerene and PA endonuclease, which suggested that fullerenes can bind to the active pocket of PA endonuclease. In a cell culture system, we found that several fullerene derivatives inhibit influenza A viral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate that fullerene derivatives are possible candidates for the development of novel anti-influenza drugs.
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shoji
authors.forename: Etsuhisa
authors.initials: E
authors.lastname: Takahashi
authors.forename: Dai
authors.initials: D
authors.lastname: Hatakeyama
authors.forename: Yuma
authors.initials: Y
authors.lastname: Iwai
authors.forename: Yuka
authors.initials: Y
authors.lastname: Morita
authors.forename: Riku
authors.initials: R
authors.lastname: Shirayama
authors.forename: Noriko
authors.initials: N
authors.lastname: Echigo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Mashino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okutani
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuzuhara
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000502:physiology; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D037741:Fullerenes; C061290:PA protein, influenza viruses; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase; C069837:fullerene C60