Rechter Sabine, König Tanja, Auerochs Sabrina, Thulke Stefanie, Walter Hauke, Dörnenburg Heike, Walter Christian, Marschall Manfred
Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Germany.
Antiviral Res. 2006 Dec;72(3):197-206. doi: 10.1016/j.antiviral.2006.06.004. Epub 2006 Jun 30.
Natural substances offer interesting pharmacological perspectives for antiviral drug development in regard to broad-spectrum antiviral properties and novel modes of action. In this study we analyzed polysaccharide fractions isolated from Arthrospira platensis. Fractions containing intracellular or extracellular spirulan-like molecules showed a pronounced antiviral activity in the absence of cytotoxic effects. Using specific assays for the quantification of viral replication in vitro, these substances exhibited strong inhibition of human cytomegalovirus, herpes simplex virus type 1, human herpesvirus type 6 and human immunodeficiency virus type 1, while only weak or no inhibition was noted for Epstein-Barr virus and influenza A virus. Considering herpesviruses, antiviral effects were most pronounced when the cells were preincubated with the substances prior to the addition of virus, indicating that antiviral action may be primarily targeted to virus entry. However, an inspection of the inhibition of human cytomegalovirus protein synthesis clearly demonstrated that intracellular steps also contributed to the antiviral effect. In the case of human immunodeficiency virus, inhibition occurred at a stage later than viral entry. Thus, spirulan-like substances possess a marked antiherpesviral and anti-HIVactivity based on different modes of action. Further development of these substances might yield novel candidates of broad-spectrum antiviral drugs.
就广谱抗病毒特性和新的作用模式而言,天然物质为抗病毒药物开发提供了有趣的药理学前景。在本研究中,我们分析了从钝顶螺旋藻中分离出的多糖组分。含有细胞内或细胞外类螺旋藻分子的组分在无细胞毒性作用的情况下表现出显著的抗病毒活性。使用体外病毒复制定量的特定检测方法,这些物质对人巨细胞病毒、1型单纯疱疹病毒、6型人类疱疹病毒和1型人类免疫缺陷病毒表现出强烈抑制作用,而对EB病毒和甲型流感病毒仅表现出微弱抑制或无抑制作用。对于疱疹病毒,当在添加病毒之前将细胞与这些物质预孵育时,抗病毒效果最为明显,这表明抗病毒作用可能主要针对病毒进入。然而,对人巨细胞病毒蛋白质合成抑制的检查清楚地表明,细胞内步骤也对抗病毒作用有贡献。就人类免疫缺陷病毒而言,抑制发生在病毒进入后的阶段。因此,类螺旋藻物质基于不同的作用模式具有显著的抗疱疹病毒和抗HIV活性。这些物质的进一步开发可能会产生新型广谱抗病毒药物候选物。