DAS181 Inhibits H5N1 Influenza Virus Infection of Human Lung Tissues

被引：54

作者：

Chan, Renee W. Y. ^{[1
,2
]}

Chan, Michael C. W. ^{[2
]}

Wong, Adam C. N. ^{[1
]}

Karamanska, Rositsa ^{[4
]}

Dell, Anne ^{[4
]}

Haslam, Stuart M. ^{[4
]}

Sihoe, Alan D. L. ^{[3
]}

Chui, W. H. ^{[3
]}

Triana-Baltzer, Gallen ^{[5
]}

Li, Qixiang ^{[5
]}

Peiris, J. S. Malik ^{[2
]}

Fang, Fang ^{[5
]}

Nicholls, John M. ^{[1
]}

机构：

[1] Univ Hong Kong, Dept Pathol, Pok Fu Lam, Hong Kong, Peoples R China

[2] Univ Hong Kong, Dept Microbiol, Pok Fu Lam, Hong Kong, Peoples R China

[3] Univ Hong Kong, Dept Cardiothorac Surg, Pok Fu Lam, Hong Kong, Peoples R China

[4] Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Div Mol Biosci, London SW7 2AZ, England

[5] NexBio Inc, San Diego, CA 92121 USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2009年 / 53卷 / 09期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

SIALIDASE FUSION PROTEIN; LOWER RESPIRATORY-TRACT; HUMAN AIRWAY EPITHELIUM; RECEPTOR SPECIFICITY; A H5N1; CELLS; HEMAGGLUTININ; BINDING; SITES; MICE;

D O I：

10.1128/AAC.00389-09

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

DAS181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing the virus receptor, sialic acid (Sia), from the adjacent glycan structures. DAS181 and its analogues have previously been shown to be potently active against multiple strains of seasonal and avian influenza virus strains in several experimental models, including cell lines, mice, and ferrets. Here we demonstrate that DAS181 treatment leads to desialylation of both alpha 2-6-linked and alpha 2-3-linked Sia in ex vivo human lung tissue culture and primary pneumocytes. DAS181 treatment also effectively protects human lung tissue and pneumocytes against the highly pathogenic avian influenza virus H5N1 (A/Vietnam/3046/2004). Two doses of DAS181 treatment given 12 h apart were sufficient to block H5N1 infection in the ex vivo lung tissue culture. These findings support the potential value of DAS181 as a broad-spectrum therapeutic agent against influenza viruses, especially H5N1.

引用

页码：3935 / 3941

页数：7

共 20 条

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