Weiler B E, Schröder H C, Stefanovich V, Stewart D, Forrest J M, Allen L B, Bowden B J, Kreuter M H, Voth R, Müller W E
Institut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universität, Mainz, F.R.G.
J Gen Virol. 1990 Sep;71 ( Pt 9):1957-63. doi: 10.1099/0022-1317-71-9-1957.
Sulphoevernan is a sulphated alpha-1----3, 1----4 polyglucan (Mr 20,000) with a helical structure. This compound effectively inhibits both human immunodeficiency virus type 1 (HIV-1) and type 2 infection of cells in vitro at concentrations around 0.5 micrograms/ml. Moreover, the compound completely inhibits HIV-1-induced syncytium formation at a concentration of 1 microgram/ml. Competition experiments with 35S-labelled sulphoevernan revealed that the mannose-specific lectin from Narcissus pseudonarcissus prevented binding of sulphoevernan to HIV-1, whereas the antibody OKT4A did not reduce the amount of sulphoevernan bound to MT-2 cells. These data indicate that the non-cytotoxic polymer sulphoevernan binds to the virus rather than to the host cell. In vivo studies, using Rauscher leukaemia virus in NMRI mice, revealed that, at a daily dose of 20 mg/kg, the animals were protected against virus-induced increases in spleen weight. From these in vitro and in vivo data we conclude that sulphoevernan has potential in the treatment of acquired immunodeficiency syndrome.
磺基埃弗南是一种具有螺旋结构的硫酸化α-1----3、1----4多聚糖(分子量20,000)。该化合物在体外浓度约为0.5微克/毫升时能有效抑制1型和2型人类免疫缺陷病毒(HIV-1和HIV-2)对细胞的感染。此外,该化合物在浓度为1微克/毫升时能完全抑制HIV-1诱导的合胞体形成。用35S标记的磺基埃弗南进行的竞争实验表明,水仙的甘露糖特异性凝集素可阻止磺基埃弗南与HIV-1结合,而抗体OKT4A并未减少磺基埃弗南与MT-2细胞的结合量。这些数据表明,无细胞毒性的聚合物磺基埃弗南与病毒而非宿主细胞结合。在体内研究中,给NMRI小鼠注射劳氏肉瘤病毒,结果显示,每日剂量为20毫克/千克时,动物可免受病毒诱导的脾脏重量增加的影响。从这些体外和体内数据我们得出结论,磺基埃弗南在获得性免疫缺陷综合征的治疗中具有潜力。