RRC ID 27715
Author Shoji M, Takahashi E, Hatakeyama D, Iwai Y, Morita Y, Shirayama R, Echigo N, Kido H, Nakamura S, Mashino T, Okutani T, Kuzuhara T.
Title Anti-influenza activity of c60 fullerene derivatives.
Journal PLoS One
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.
Volume 8(6)
Pages e66337
Published 2013-1-1
DOI 10.1371/journal.pone.0066337
PII PONE-D-13-01705
PMID 23785493
PMC PMC3681905
MeSH Animals Antiviral Agents / chemistry Antiviral Agents / pharmacology* Antiviral Agents / toxicity Cell Line Dogs Enzyme Activation / drug effects Fullerenes / chemistry Fullerenes / pharmacology* Fullerenes / toxicity Influenza A Virus, H1N1 Subtype / drug effects Influenza A Virus, H1N1 Subtype / physiology Influenza A Virus, H3N2 Subtype / drug effects Influenza A Virus, H3N2 Subtype / physiology Influenza A virus / drug effects* Influenza A virus / physiology Molecular Conformation Molecular Docking Simulation RNA-Dependent RNA Polymerase / antagonists & inhibitors Viral Proteins / antagonists & inhibitors Viral Proteins / genetics Viral Proteins / metabolism
IF 2.74
Times Cited 38
DNA material pBMSA-PA (RDB01971)