Identification of influenza A nucleoprotein as an antiviral target

Richard Y. Kao; Dan Yang; Lai Shan Lau; Wayne H.W. Tsui; Lihong Hu; Jun Dai; Mei Po Chan; Che Man Chan; Pui Wang; Bo Jian Zheng; Jian Sun; Jian Dong Huang; Jason Madar; Guanhua Chen; Honglin Chen; Yi Guan; Kwok Yung Yuen

doi:10.1038/nbt.1638

Identification of influenza A nucleoprotein as an antiviral target

Richard Y. Kao, Dan Yang, Lai Shan Lau, Wayne H.W. Tsui, Lihong Hu, Jun Dai, Mei Po Chan, Che Man Chan, Pui Wang, Bo Jian Zheng, Jian Sun, Jian Dong Huang, Jason Madar, Guanhua Chen, Honglin Chen, Yi Guan, Kwok Yung Yuen

Research output: Contribution to journal › Article › peer-review

225 Citations (Scopus)

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 (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.

Original language	English
Pages (from-to)	600-605
Number of pages	6
Journal	Nature Biotechnology
Volume	28
Issue number	6
DOIs	https://doi.org/10.1038/nbt.1638
Publication status	Published - Jun 2010
Externally published	Yes

ASJC Scopus Subject Areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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10.1038/nbt.1638

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title = "Identification of influenza A nucleoprotein as an antiviral target",

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 (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.",

author = "Kao, {Richard Y.} and Dan Yang and Lau, {Lai Shan} and Tsui, {Wayne H.W.} and Lihong Hu and Jun Dai and Chan, {Mei Po} and Chan, {Che Man} and Pui Wang and Zheng, {Bo Jian} and Jian Sun and Huang, {Jian Dong} and Jason Madar and Guanhua Chen and Honglin Chen and Yi Guan and Yuen, {Kwok Yung}",

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AU - Kao, Richard Y.

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AU - Lau, Lai Shan

AU - Tsui, Wayne H.W.

AU - Hu, Lihong

AU - Dai, Jun

AU - Chan, Mei Po

AU - Chan, Che Man

AU - Wang, Pui

AU - Zheng, Bo Jian

AU - Sun, Jian

AU - Huang, Jian Dong

AU - Madar, Jason

AU - Chen, Guanhua

AU - Chen, Honglin

AU - Guan, Yi

AU - Yuen, Kwok Yung

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AB - 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.

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Identification of influenza A nucleoprotein as an antiviral target

Abstract

ASJC Scopus Subject Areas

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