Prevention of influenza pneumonitis by sialic acid-conjugated dendritic polymers
Prevention of influenza pneumonitis by sialic acid-conjugated dendritic polymers
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DOI：
10.1086/344316
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发表时间：
2002-11-01
影响因子：
6.4
通讯作者：
Baker, JR
中科院分区：
文献类型：
--
作者：
Landers, JJ;Cao, ZY;Baker, JR
甲型流感病毒感染开始于病毒包膜上的血凝素糖蛋白与细胞膜唾液酸（SA）结合。由于毒性，游离SA单体不能在体内阻断血凝素粘附。评价了多价第4代（G4）SA-共轭聚酰胺胺（PAMAM）树状聚合物（G4-SA）作为预防3种甲型流感亚型（H1N1、H2 N2和H3 N2）粘附的方法。在血凝抑制试验中，发现G4-SA在比SA单体低32-170倍的浓度下抑制所有H3 N2和5种H1N1流感亚型中的3种。而G4-SA对H2 N2亚型或5种H1N1亚型毒株中的2种无血凝抑制作用。体内实验表明，G4-SA完全预防了小鼠流感肺炎模型中H3 N2亚型的感染，但不能有效预防H2 N2亚型引起的肺炎。多价结合抑制剂具有作为抗病毒治疗剂的潜力，但必须解决与菌株特异性相关的问题。
Influenza A viral infection begins by hemagglutinin glycoproteins on the viral envelope binding to cell membrane sialic acid (SA). Free SA monomers cannot block hemagglutinin adhesion in vivo because of toxicity. Polyvalent, generation 4 (G4) SA-conjugated polyamidoamine (PAMAM) dendrimer (G4-SA) was evaluated as a means of preventing adhesion of 3 influenza A subtypes (H1N1, H2N2, and H3N2). In hemagglutination-inhibition assays, G4-SA was found to inhibit all H3N2 and 3 of 5 H1N1 influenza subtype strains at concentrations 32-170 times lower than those of SA monomers. In contrast, G4-SA had no ability to inhibit hemagglutination with H2N2 subtypes or 2 of 5 H1N1 subtype strains. In vivo experiments showed that G4-SA completely prevented infection by a H3N2 subtype in a murine influenza pneumonitis model but was not effective in preventing pneumonitis caused by an H2N2 subtype. Polyvalent binding inhibitors have potential as antiviral therapeutics, but issues related to strain specificity must be resolved.