Giuseppe
Emeritus
[Source: Nature Biotechnology, <cite cite="http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.1638.html">Access : Identification of influenza A nucleoprotein as an antiviral target : Nature Biotechnology</cite>. Extract, edited.]
Letter
Nature Biotechnology
Published online: 30 May 2010 | doi:10.1038/nbt.1638
Identification of influenza A nucleoprotein as an antiviral target
Richard Y Kao 1,2,3, Dan Yang 4, Lai-Shan Lau 1, Wayne H W Tsui 1, Lihong Hu 4, Jun Dai 1,2, Mei-Po Chan 1, Che-Man Chan 1, Pui Wang 1, Bo-Jian Zheng 1,2,3, Jian Sun 4, Jian-Dong Huang 5, Jason Madar 6, Guanhua Chen 4, Honglin Chen 1,2,3, Yi Guan 1,2,3 & Kwok-Yung Yuen 1,2,3
Abstract
Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains1, 2, 3, 4, 5. Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly6, 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 (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.
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Letter
Nature Biotechnology
Published online: 30 May 2010 | doi:10.1038/nbt.1638
Identification of influenza A nucleoprotein as an antiviral target
Richard Y Kao 1,2,3, Dan Yang 4, Lai-Shan Lau 1, Wayne H W Tsui 1, Lihong Hu 4, Jun Dai 1,2, Mei-Po Chan 1, Che-Man Chan 1, Pui Wang 1, Bo-Jian Zheng 1,2,3, Jian Sun 4, Jian-Dong Huang 5, Jason Madar 6, Guanhua Chen 4, Honglin Chen 1,2,3, Yi Guan 1,2,3 & Kwok-Yung Yuen 1,2,3
Abstract
Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains1, 2, 3, 4, 5. Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly6, 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 (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.
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