DAS181 Inhibits H5N1 Influenza Virus Infection of Human Lung Tissues
DAS181 Inhibits H5N1 Influenza Virus Infection of Human Lung Tissues
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DOI：
10.1128/aac.00389-09
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发表时间：
2009-09-01
影响因子：
4.9
通讯作者：
Nicholls, John M.
中科院分区：
文献类型：
--
作者：
Chan, Renee W. Y.;Chan, Michael C. W.;Nicholls, John M.
DAS 181是一种新型候选抗流感病毒治疗药物，其作用机制是从相邻聚糖结构中去除病毒受体唾液酸（Sia）。先前已在几种实验模型（包括细胞系、小鼠和雪貂）中证明DAS 181及其类似物对多种季节性流感病毒株和禽流感病毒株具有强效活性。在此，我们证明了DAS 181处理导致离体人肺组织培养物和原代肺细胞中α 2-6-连接和α 2-3-连接Sia的去唾液酸化。DAS 181处理还可有效保护人肺组织和肺细胞免受高致病性禽流感病毒H5 N1的侵害（A/Vietnam/3046/2004）。间隔12小时给予两剂DAS 181治疗足以阻断离体肺组织培养物中的H5 N1感染。这些结果支持DAS 181作为抗流感病毒（尤其是H5 N1）的广谱治疗剂的潜在价值。
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.