Identification of influenza A nucleoprotein as an antiviral target

Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains(1,2,3,4,5). Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly(6,7,8,9), creating a need for new antiviral...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2010
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097325/
https://www.ncbi.nlm.nih.gov/pubmed/20512121
http://dx.doi.org/10.1038/nbt.1638
Descripción
Sumario:Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains(1,2,3,4,5). Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly(6,7,8,9), 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nbt.1638) contains supplementary material, which is available to authorized users.

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