Hayashi K, Hayashi T, Kojima I
Department of Virology, Toyama Medical and Pharmaceutical University, Japan.
AIDS Res Hum Retroviruses. 1996 Oct 10;12(15):1463-71. doi: 10.1089/aid.1996.12.1463.
A sulfated polysaccharide named calcium spirulan (Ca-SP) has been isolated from a sea alga, Spirulina platensis, as an antiviral component. The anti-human immunodeficiency virus type 1 (HIV-1) and anti-herpes simplex virus type 1 (HSV-1) activities of Ca-SP were compared with those of dextran sulfate (DS) as a representative sulfated polysaccharide. Anti-HIV-1 activities of these agents were measured by three different assays: viability of acutely infected CD4-positive cells, or a cytopathology assay; determination of HIV-1 p24 antigen released into culture supernatants; and inhibition of HIV-induced syncytium formation. Anti-HSV-1 activity was assessed by plaque yield reduction. In addition, their effects on the blood coagulation processes and stability in the blood were evaluated. These data indicate that Ca-SP is a potent antiviral agent against both HIV-1 and HSV-1. Furthermore, Ca-SP is quite promising as an anti-HIV agent because even at low concentrations of Ca-SP an enhancement of virus-induced syncytium formation was not observed, as was observed in DS-treated cultures, Ca-SP had very low anticoagulant activity, and showed a much longer half-life in the blood of mice when compared with that of DS. Thus, Ca-SP can be a candidate agent for an anti-HIV therapeutic drug that might overcome the disadvantages observed in many sulfated polysaccharides. When the role of chelation of calcium ion with sulfate groups was examined by removing calcium or its replacement by sodium, the presence of calcium ion in the molecule was shown to be essential for the dose-dependent inhibition of cytopathic effect and syncytium formation induced by HIV-1.
一种名为螺旋藻钙（Ca-SP）的硫酸化多糖已从海藻钝顶螺旋藻中分离出来，作为一种抗病毒成分。将Ca-SP的抗1型人类免疫缺陷病毒（HIV-1）和抗1型单纯疱疹病毒（HSV-1）活性与作为代表性硫酸化多糖的硫酸葡聚糖（DS）的活性进行了比较。通过三种不同的试验来测定这些药物的抗HIV-1活性：急性感染的CD4阳性细胞的活力，即细胞病变试验；测定释放到培养上清液中的HIV-1 p24抗原；以及抑制HIV诱导的合胞体形成。通过噬斑形成率降低来评估抗HSV-1活性。此外，还评估了它们对血液凝固过程的影响以及在血液中的稳定性。这些数据表明Ca-SP是一种针对HIV-1和HSV-1的强效抗病毒剂。此外，Ca-SP作为一种抗HIV药物很有前景，因为即使在低浓度的Ca-SP下，也未观察到病毒诱导的合胞体形成增强，而在DS处理的培养物中则观察到了这种增强；Ca-SP具有非常低的抗凝活性，并且与DS相比，在小鼠血液中的半衰期长得多。因此，Ca-SP可以成为一种抗HIV治疗药物的候选药物，该药物可能克服许多硫酸化多糖中观察到的缺点。当通过去除钙或将其替换为钠来研究钙离子与硫酸根基团螯合的作用时，发现分子中钙离子的存在对于剂量依赖性抑制HIV-1诱导的细胞病变效应和合胞体形成至关重要。
