Identification of influenza A nucleoprotein as an antiviral target

被引：219

作者：

Kao, Richard Y. ^{[1
,3
]}

Yang, Dan ^{[4
]}

Lau, Lai-Shan ^{[1
]}

Tsui, Wayne H. W. ^{[1
]}

Hu, Lihong ^{[4
]}

Dai, Jun ^{[1
,2
]}

Chan, Mei-Po ^{[1
]}

Chan, Che-Man ^{[1
]}

Wang, Pui ^{[1
]}

Zheng, Bo-Jian ^{[1
,3
]}

Sun, Jian ^{[4
]}

Huang, Jian-Dong ^{[5
]}

Madar, Jason

Chen, Guanhua ^{[4
]}

Chen, Honglin ^{[1
,3
]}

Guan, Yi ^{[1
,3
]}

Yuen, Kwok-Yung ^{[1
,3
]}

机构：

[1] Univ Hong Kong, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China

[2] Univ Hong Kong, Res Ctr Infect & Immunol, Hong Kong, Hong Kong, Peoples R China

[3] Univ Hong Kong, State Key Lab Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China

[4] Univ Hong Kong, Dept Chem, Hong Kong, Hong Kong, Peoples R China

[5] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China

来源：

NATURE BIOTECHNOLOGY | 2010年 / 28卷 / 06期

关键词：

OSELTAMIVIR-RESISTANT INFLUENZA; SMALL-MOLECULE INHIBITORS; VIRUS NUCLEOPROTEIN; NUCLEAR-LOCALIZATION; RIBONUCLEOPROTEIN COMPLEXES; VIRAL NUCLEOPROTEIN; CHEMICAL GENETICS; RNA-BINDING; REPLICATION; INFECTIONS;

D O I：

10.1038/nbt.1638

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains(1-5). Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly(6-9), 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.

引用

页码：600 / U88

页数：8

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