Landers Jeffrey J, Cao Zhengyi, Lee Inhan, Piehler Lars T, Myc Piotr P, Myc Andrzej, Hamouda Tarek, Galecki Andrzej T, Baker James R
Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, University of Michigan, Ann Arbor, Michigan 48109, USA.
J Infect Dis. 2002 Nov 1;186(9):1222-30. doi: 10.1086/344316. Epub 2002 Oct 8.
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.
甲型流感病毒感染始于病毒包膜上的血凝素糖蛋白与细胞膜唾液酸（SA）结合。游离的SA单体由于毒性在体内无法阻断血凝素的黏附。评估了多价第4代（G4）SA共轭聚酰胺胺（PAMAM）树枝状大分子（G4-SA）作为预防3种甲型流感病毒亚型（H1N1、H2N2和H3N2）黏附的一种手段。在血凝抑制试验中，发现G4-SA抑制所有H3N2以及5株H1N1流感病毒亚型中的3株时所需浓度比SA单体低32至170倍。相比之下，G4-SA无法抑制H2N2亚型或5株H1N1亚型中的2株的血凝反应。体内实验表明，在小鼠流感肺炎模型中，G4-SA完全预防了H3N2亚型的感染，但在预防由H2N2亚型引起的肺炎方面无效。多价结合抑制剂有作为抗病毒治疗药物的潜力，但与毒株特异性相关的问题必须得到解决。
