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抑制流感病毒复制的新型聚阴离子

Novel Polyanions Inhibiting Replication of Influenza Viruses.

作者信息

Ciejka Justyna, Milewska Aleksandra, Wytrwal Magdalena, Wojarski Jacek, Golda Anna, Ochman Marek, Nowakowska Maria, Szczubialka Krzysztof, Pyrc Krzysztof

机构信息

Faculty of Chemistry, Jagiellonian University, Krakow, Poland Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.

Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.

出版信息

Antimicrob Agents Chemother. 2016 Mar 25;60(4):1955-66. doi: 10.1128/AAC.02183-15. Print 2016 Apr.

Abstract

Novel sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) and N-sulfonated chitosan (NSCH) have been synthesized, and their activity against influenza A and B viruses has been studied and compared with that of a series of carrageenans, marine polysaccharides of well-documented anti-influenza activity. NSPAHs were found to be nontoxic and very soluble in water, in contrast to gel-forming and thus generally poorly soluble carrageenans.In vitroandex vivostudies using susceptible cells (Madin-Darby canine kidney epithelial cells and fully differentiated human airway epithelial cultures) demonstrated the antiviral effectiveness of NSPAHs. The activity of NSPAHs was proportional to the molecular mass of the chain and the degree of substitution of amino groups with sulfonate groups. Mechanistic studies showed that the NSPAHs and carrageenans inhibit influenza A and B virus assembly in the cell.

摘要

已合成了聚(烯丙胺盐酸盐)的新型磺化衍生物(NSPAHs)和N-磺化壳聚糖(NSCH),并研究了它们对甲型和乙型流感病毒的活性,并与一系列角叉菜胶(具有充分文献记载的抗流感活性的海洋多糖)进行了比较。发现NSPAHs无毒且极易溶于水,这与形成凝胶因而通常溶解性较差的角叉菜胶不同。使用易感细胞(马-达二氏犬肾上皮细胞和完全分化的人气道上皮培养物)进行的体外和体内研究证明了NSPAHs的抗病毒有效性。NSPAHs的活性与链的分子量以及氨基被磺酸根基团取代的程度成正比。机理研究表明,NSPAHs和角叉菜胶可抑制细胞中甲型和乙型流感病毒的组装。

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