Mochalova L V, Tuzikov A B, Marinina V P, Gambaryan A S, Byramova N E, Bovin N V, Matrosovich M N
Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow.
Antiviral Res. 1994 Apr;23(3-4):179-90. doi: 10.1016/0166-3542(94)90016-7.
A new approach to anti-influenza chemotherapy is based on the development of synthetic inhibitors of virus attachment to host cells. These inhibitors are prepared by anchoring the minimum receptor determinant of influenza virus, sialic acid, to polymeric or liposomal carriers. In this study, a series of poly(acrylic acid-co-acrylamides) and dextrans bearing pendant glycylamidobenzylsialoside groups were synthesized and evaluated for their binding to a panel of influenza A and B virus strains and for their ability to inhibit virus infectivity in cell culture. Significant type-, subtype-, and strain-specific variation in virus susceptibility to the synthetic inhibitors was observed. Among the viruses tested, H3 subtype strains evolved in humans since 1975 were the most sensitive, while the earlier H3 viruses and the type B strains were resistant. The virus-inhibitory potency of the polymeric sialosides correlated with their bindings to the virus, and was dependent on the virus affinity for the ligand, the density of the ligand, and the nature and molecular mass of the polymeric carrier. In embryonated eggs, the antiviral effect of poly(acryloyl-glycylamidobenzylsialoside-co-acrylic acid) was comparable to that of equine alpha 2-macroglobulin.
一种抗流感化疗的新方法基于开发病毒附着于宿主细胞的合成抑制剂。这些抑制剂是通过将流感病毒的最小受体决定簇唾液酸锚定到聚合物或脂质体载体上制备的。在本研究中，合成了一系列带有侧链甘氨酰胺苄基唾液酸苷基团的聚丙烯酸-丙烯酰胺共聚物和葡聚糖，并评估了它们与一组甲型和乙型流感病毒株的结合情况以及在细胞培养中抑制病毒感染性的能力。观察到合成抑制剂对病毒的敏感性存在显著的型、亚型和株特异性差异。在测试的病毒中，1975年以来在人类中进化的H3亚型毒株最为敏感，而早期的H3病毒和B型毒株具有抗性。聚合唾液酸苷的病毒抑制效力与其与病毒的结合相关，并取决于病毒对配体的亲和力、配体的密度以及聚合物载体的性质和分子量。在鸡胚中，聚丙烯酰甘氨酰胺苄基唾液酸苷-丙烯酸共聚物的抗病毒效果与马α2-巨球蛋白相当。
