Identification of influenza A nucleoprotein as an antiviral target

Nat Biotechnol. 2010 Jun;28(6):600-5. doi: 10.1038/nbt.1638. Epub 2010 May 30.


Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains. Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly, creating a need for new antiviral targets and new drugs for influenza virus infections. Using forward chemical genetics, we have identified influenza A nucleoprotein (NP) as a druggable target and found a small-molecule compound, nucleozin, that triggers the aggregation of NP and inhibits its nuclear accumulation. Nucleozin impeded influenza A virus replication in vitro with a nanomolar median effective concentration (EC(50)) and protected mice challenged with lethal doses of avian influenza A H5N1. Our results demonstrate that viral NP is a valid target for the development of small-molecule therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Binding Sites
  • Cell Line
  • Disease Models, Animal
  • Dogs
  • Female
  • Humans
  • Influenza A Virus, H5N1 Subtype / drug effects
  • Influenza A virus / chemistry*
  • Influenza A virus / drug effects*
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Nucleoproteins / antagonists & inhibitors*
  • Nucleoproteins / chemistry
  • Orthomyxoviridae Infections / virology
  • Protein Structure, Quaternary
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / chemistry


  • Antiviral Agents
  • Nucleoproteins
  • Small Molecule Libraries
  • Viral Proteins