Zhang Mei, Cheung Peter C K, Ooi Vincent E C, Zhang Lina
Department of Biology, University Science Centre, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Carbohydr Res. 2004 Sep 13;339(13):2297-301. doi: 10.1016/j.carres.2004.07.003.
Six water-insoluble fractions of fungal beta-glucans extracted by hot alkali (TM8-1 to TM8-6) from the sclerotia of Pleurotus tuber-regium (PTR) having different molecular weights (M(w)) were sulfated to give their corresponding water-soluble derivatives (S-TM8-1 to S-TM8-6) with the degree of sulfation (DS) ranging from 1.14 to 1.74. The in vitro anti-viral activities of the native beta-glucans (TM8s) and their sulfated derivatives (S-TM8s) were evaluated by the cytopathic effect assay (CPE) and the plaque reduction assay (PRA) against four kinds of viruses, including herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), respiratory syncytial virus (RSV), and influenza A virus (Flu A). Although TM8s were inactive in inhibiting the viral replication in cell cultures, the S-TM8 fractions with the defined M(w) range had potent anti-viral activity against HSV-1 and HSV-2 as shown by the CPE assay. The PRA results suggested that S-TM8 fractions seemed to exert their anti-viral effect by binding to the viral particles, preventing the latter from infecting the host cells. It was plausible that the negative charges on the polymer chain of S-TM8 could interact with the positively charged glycoproteins on the surface of HSV, minimizing the interaction between the HSV and the negatively charged host cells. The anti-viral activity of the S-TM8s might also be explained by their more extended chain conformation in solution due to an increase in one of their molecular parameter, persistence length (q), as compared to the native TM8s. The potential use of S-TM8s as a water-soluble anti-HSV agent is discussed.
用热碱从虎奶菇菌核中提取的六种水不溶性真菌β-葡聚糖级分(TM8-1至TM8-6)具有不同的分子量(M(w)),将其硫酸化得到相应的水溶性衍生物(S-TM8-1至S-TM8-6),硫酸化程度(DS)在1.14至1.74之间。通过细胞病变效应试验(CPE)和蚀斑减少试验(PRA),针对四种病毒,包括单纯疱疹病毒1型(HSV-1)、单纯疱疹病毒2型(HSV-2)、呼吸道合胞病毒(RSV)和甲型流感病毒(Flu A),评估了天然β-葡聚糖(TM8s)及其硫酸化衍生物(S-TM8s)的体外抗病毒活性。尽管TM8s在细胞培养中抑制病毒复制方面无活性,但CPE试验表明,具有特定M(w)范围的S-TM8级分对HSV-1和HSV-2具有强大的抗病毒活性。PRA结果表明,S-TM8级分似乎通过与病毒颗粒结合发挥其抗病毒作用,阻止病毒颗粒感染宿主细胞。S-TM8聚合物链上的负电荷可能与HSV表面带正电荷的糖蛋白相互作用,使HSV与带负电荷的宿主细胞之间的相互作用最小化,这似乎是合理的。与天然TM8s相比,S-TM8s的抗病毒活性也可能归因于其在溶液中由于分子参数之一的持久长度(q)增加而具有更伸展的链构象。本文还讨论了S-TM8s作为水溶性抗HSV剂的潜在用途。