Discovery of novel antiviral agents directed against the influenza A virus nucleoprotein using photo-cross-linked chemical arrays

Kyoji Hagiwara, Yasumitsu Kondoh, Atsushi Ueda, Kazunori Yamada, Hideo Goto, Toshiki Watanabe, Tadashi Nakata, Hiroyuki Osada, Yoko Aida

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

The nucleoprotein (NP) of the influenza virus is expressed in the early stage of infection and plays important roles in numerous steps of viral replication. NP is relatively well conserved compared with viral surface spike proteins. This study experimentally demonstrates that NP is a novel target for the development of new antiviral drugs against the influenza virus. First, artificial analogs of mycalamide A in a chemical array bound specifically with high affinity to NP. Second, the compounds inhibited multiplication of the influenza virus. Furthermore, surface plasmon resonance imaging experiments demonstrated that the binding activity of each compound to NP correlated with its antiviral activity. Finally, it was shown that these compounds bound NP within the N-terminal 110-amino acid region but their binding abilities were dramatically reduced when the N-terminal 13-amino acid tail was deleted, suggesting that the compounds might bind to this region, which mediates the nuclear transport of NP and its binding to viral RNA. These data suggest that compound binding to the N-terminal 13-amino acid tail region may inhibit viral replication by inhibiting the functions of NP. Collectively, these results strongly suggest that chemical arrays are convenient tools for the screening of viral product inhibitors.

Original languageEnglish
Pages (from-to)721-727
Number of pages7
JournalBiochemical and biophysical research communications
Volume394
Issue number3
DOIs
Publication statusPublished - 2010 Apr 9
Externally publishedYes

Keywords

  • Antiviral agents
  • Chemical array
  • Influenza virus
  • Mycalamide A
  • NP-binding compound
  • Nucleoprotein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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