Cardozo Francielle Tramontini Gomes de Sousa, Camelini Carla Maísa, Leal Paulo César, Kratz Jadel Müller, Nunes Ricardo José, Mendonça Margarida Matos de, Simões Cláudia Maria Oliveira
Department of Infectious and Parasitic Diseases, Laboratory of Virology, Institute of Tropical Medicine, Universidade de São Paulo, São Paulo, Brazil.
Intervirology. 2014;57(6):375-83. doi: 10.1159/000365194. Epub 2014 Oct 25.
To study the anti-herpes simplex virus (HSV) activity of a (1→6)-(1→3)-β-D-glucan isolated from Agaricus brasiliensis fruiting bodies (FR) as well as its chemically sulfated derivative (FR-S).
The antiherpetic activity and mechanism of action was studied by viral plaque assay applying different methodological strategies.
Although FR presented no in vitro antiherpetic action at 1 mg/ml, FR-S displayed promising anti-HSV-1 and anti-HSV-2 activities in both simultaneous and postinfection treatments, resulting in selectivity indices (CC₅₀/EC₅₀) higher than 393. FR-S had no virucidal effect, but significantly suppressed HSV-1 (EC₅₀ = 0.32 µg/ml) and HSV-2 (EC₅₀ = 0.10 µg/ml) adsorption. FR-S was less effective on adsorption inhibition of mutant virus strains devoid of gC (HSV-1 gC⁻39 and HSV-2 gCneg1), indicating a possible interaction with this glycoprotein. The reduction of viral adsorption upon cell pretreatment with FR-S also suggests its interaction with cellular components. FR-S inhibited HSV-1 (EC₅₀ = 8.39 µg/ml) and HSV-2 (EC₅₀ = 2.86 µg/ml) penetration more efficiently than heparin. FR-S reduced HSV-1 and HSV-2 cell-to-cell spread. A synergic effect between FR-S and acyclovir was also detected.
FR-S displays an interesting mechanism of antiviral action and represents a promising candidate for the treatment and/or prevention of herpetic infections, to be used as a single therapeutic agent or in combination with acyclovir.
研究从巴西蘑菇子实体（FR）中分离得到的（1→6）-（1→3）-β-D-葡聚糖及其化学硫酸化衍生物（FR-S）的抗单纯疱疹病毒（HSV）活性。
采用不同的方法策略，通过病毒蚀斑试验研究其抗疱疹活性及作用机制。
尽管FR在1mg/ml时未表现出体外抗疱疹作用，但FR-S在同时感染和感染后处理中均显示出有前景的抗HSV-1和抗HSV-2活性，其选择性指数（CC₅₀/EC₅₀）高于393。FR-S没有杀病毒作用，但能显著抑制HSV-1（EC₅₀ = 0.32μg/ml）和HSV-2（EC₅₀ = 0.10μg/ml）的吸附。FR-S对缺乏gC的突变病毒株（HSV-1 gC⁻39和HSV-2 gCneg1）的吸附抑制作用较弱，表明其可能与这种糖蛋白相互作用。用FR-S对细胞进行预处理后病毒吸附的减少也表明其与细胞成分相互作用。FR-S比肝素更有效地抑制HSV-1（EC₅₀ = 8.39μg/ml）和HSV-2（EC₅₀ = 2.86μg/ml）的穿透。FR-S减少了HSV-1和HSV-2的细胞间传播。还检测到FR-S与阿昔洛韦之间的协同作用。
FR-S显示出有趣的抗病毒作用机制，是治疗和/或预防疱疹感染的有前景的候选药物，可作为单一治疗剂或与阿昔洛韦联合使用。
