Anti-Influenza Activity of C60 Fullerene Derivatives

Masaki Shoji, Etsuhisa Takahashi, Dai Hatakeyama, Yuma Iwai, Yuka Morita, Riku Shirayama, Noriko Echigo, Hiroshi Kido, Shigeo Nakamura, Tadahiko Mashino, Takeshi Okutani, Takashi Kuzuhara

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish
Article numbere66337
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - 2013 Jun 13

Fingerprint

fullerene
Fullerenes
Endonucleases
influenza
Human Influenza
chemical derivatives
Derivatives
Viruses
Influenza A virus
Nucleoproteins
H1N1 Subtype Influenza A Virus
DNA-Directed RNA Polymerases
Southeastern Asia
Influenza in Birds
Cell culture
Pharmaceutical Preparations
drugs
Pandemics
Virus Diseases
nucleoproteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Shoji, M., Takahashi, E., Hatakeyama, D., Iwai, Y., Morita, Y., Shirayama, R., ... Kuzuhara, T. (2013). Anti-Influenza Activity of C60 Fullerene Derivatives. PLoS One, 8(6), [e66337]. https://doi.org/10.1371/journal.pone.0066337

Anti-Influenza Activity of C60 Fullerene Derivatives. / Shoji, Masaki; Takahashi, Etsuhisa; Hatakeyama, Dai; Iwai, Yuma; Morita, Yuka; Shirayama, Riku; Echigo, Noriko; Kido, Hiroshi; Nakamura, Shigeo; Mashino, Tadahiko; Okutani, Takeshi; Kuzuhara, Takashi.

In: PLoS One, Vol. 8, No. 6, e66337, 13.06.2013.

Research output: Contribution to journalArticle

Shoji, M, Takahashi, E, Hatakeyama, D, Iwai, Y, Morita, Y, Shirayama, R, Echigo, N, Kido, H, Nakamura, S, Mashino, T, Okutani, T & Kuzuhara, T 2013, 'Anti-Influenza Activity of C60 Fullerene Derivatives', PLoS One, vol. 8, no. 6, e66337. https://doi.org/10.1371/journal.pone.0066337
Shoji M, Takahashi E, Hatakeyama D, Iwai Y, Morita Y, Shirayama R et al. Anti-Influenza Activity of C60 Fullerene Derivatives. PLoS One. 2013 Jun 13;8(6). e66337. https://doi.org/10.1371/journal.pone.0066337
Shoji, Masaki ; Takahashi, Etsuhisa ; Hatakeyama, Dai ; Iwai, Yuma ; Morita, Yuka ; Shirayama, Riku ; Echigo, Noriko ; Kido, Hiroshi ; Nakamura, Shigeo ; Mashino, Tadahiko ; Okutani, Takeshi ; Kuzuhara, Takashi. / Anti-Influenza Activity of C60 Fullerene Derivatives. In: PLoS One. 2013 ; Vol. 8, No. 6.
@article{0a723326a45b4d179e090d612c0cfe05,
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.",
author = "Masaki Shoji and Etsuhisa Takahashi and Dai Hatakeyama and Yuma Iwai and Yuka Morita and Riku Shirayama and Noriko Echigo and Hiroshi Kido and Shigeo Nakamura and Tadahiko Mashino and Takeshi Okutani and Takashi Kuzuhara",
year = "2013",
month = "6",
day = "13",
doi = "10.1371/journal.pone.0066337",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Anti-Influenza Activity of C60 Fullerene Derivatives

AU - Shoji, Masaki

AU - Takahashi, Etsuhisa

AU - Hatakeyama, Dai

AU - Iwai, Yuma

AU - Morita, Yuka

AU - Shirayama, Riku

AU - Echigo, Noriko

AU - Kido, Hiroshi

AU - Nakamura, Shigeo

AU - Mashino, Tadahiko

AU - Okutani, Takeshi

AU - Kuzuhara, Takashi

PY - 2013/6/13

Y1 - 2013/6/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878968812&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878968812&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0066337

DO - 10.1371/journal.pone.0066337

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e66337

ER -