Inhibition of primary clinical isolates of human parainfluenza virus by DAS181 in cell culture and in a cotton rat model.
Inhibition of primary clinical isolates of human parainfluenza virus by DAS181 in cell culture and in a cotton rat model.
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DAS181 在细胞培养物和棉鼠模型中对人副流感病毒初级临床分离株的抑制作用。
DOI：
10.1016/j.antiviral.2013.09.014
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发表时间：
2013
影响因子：
7.6
通讯作者：
Hurwitz,JL
中科院分区：
文献类型：
--
作者：
Jones,BG;Hayden,RT;Hurwitz,JL
DAS 181是一种正在开发的用于治疗流感和人副流感病毒（hPIV）的新药。既往研究表明，DAS 181可抑制hPIV实验室菌株，但未对hPIV主要临床分离株进行检测。为了填补这一空白，我们研究了包括hPIV-2和hPIV-3在内的六种主要分离株。第一次试验表明，在0.1 - 1 nM范围内的DAS 181药物浓度下，所有病毒的体外扩增均受到重现性抑制。然后在棉鼠模型中测试hPIV-3主要临床分离株对0.3-1 mg/kg药物治疗的敏感性。结果表明，药物对下呼吸道病毒的扩增有明显的抑制作用，且可重复。总之，实验证明，DAS 181在体外和体内抑制hPIV的主要临床分离株的剂量与先前描述的抑制实验室hPIV和流感病毒分离株的剂量相似。
DAS181 is a novel drug in development for the treatment of influenza as well as human parainfluenza viruses (hPIVs). Previous studies demonstrated that DAS181 inhibited laboratory strains of hPIV, but no tests were conducted with primary clinical isolates of hPIV. To fill this gap, we studied six primary isolates including hPIV-2 and hPIV-3. First tests showed that the amplification of all virusesin vitrowas reproducibly inhibited with DAS181 drug concentrations ranging between 0.1 and 1 nM. An hPIV-3 primary clinical isolate was then tested in a cotton rat model for sensitivity to 0.3–1 mg/kg drug treatments. Results showed that virus amplification in the lower respiratory tract was significantly and reproducibly inhibited by drug. Together, experiments demonstrated that DAS181 inhibited primary clinical isolates of hPIVin vitroandin vivoat doses similar to those previously described for inhibition of laboratory hPIV and influenza virus isolates.