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- Title
Identification of influenza A nucleoprotein as an antiviral target.
- Authors
Kao, Richard Y.; Yang, Dan; Lau, Lai-Shan; Tsui, Wayne H. W.; Hu, Lihong; Dai, Jun; Chan, Mei-Po; Chan, Che-Man; Wang, Pui; Zheng, Bo-Jian; Sun, Jian; Huang, Jian-Dong; Madar, Jason; Chen, Guanhua; Chen, Honglin; Guan, Yi; Yuen, Kwok-Yung
- Abstract
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 (EC50) 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.
- Subjects
INFLUENZA A virus; INFLUENZA A virus, H5N1 subtype; AVIAN influenza; NUCLEOPROTEINS; BIOCHEMICAL genetics; LABORATORY mice
- Publication
Nature Biotechnology, 2010, Vol 28, Issue 6, p600
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt.1638