Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
Antiviral Res. 2011 Oct;92(1):108-14. doi: 10.1016/j.antiviral.2011.07.009. Epub 2011 Jul 20.
Sulfated polysaccharides are good candidates for drug discovery in the treatment of herpetic infections. Agaricus brasiliensis (syn A. subrufescens, A. blazei) is a Basidiomycete fungus native to the Atlantic forest region of Southeastern Brazil. Herein we report the chemical modification of a polysaccharide extracted from A. brasiliensis mycelia to obtain its sulfated derivative (MI-S), which presented a promising inhibitory activity against HSV-1 [KOS and 29R (acyclovir-resistant) strains] and HSV-2 strain 333, with selectivity indices (SI = CC50/IC50) higher than 439, 208, and 562, respectively. The mechanisms underlying this inhibitory activity were scrutinized by plaque assay with different methodological strategies. MI-S had no virucidal effects, but inhibited HSV-1 and HSV-2 attachment, penetration, and cell-to-cell spread, as well as reducing the expression of HSV-1 ICP27, UL42, gB, and gD proteins. MI-S also presented synergistic antiviral effect with acyclovir. These results suggest that MI-S presents multiple modes of anti-HSV action.
硫酸化多糖是治疗疱疹感染药物发现的候选物。巴西蘑菇（同义词为 A. subrufescens，A. blazei）是一种担子菌真菌，原产于巴西东南部的大西洋森林地区。本文报道了从巴西蘑菇菌丝体中提取的多糖的化学修饰，得到其硫酸化衍生物（MI-S），该衍生物对 HSV-1[KOS 和 29R（无环鸟苷耐药）株]和 HSV-2 株 333 具有有前景的抑制活性，选择性指数（SI=CC50/IC50）分别高于 439、208 和 562。通过使用不同方法策略的蚀斑试验来仔细研究这种抑制活性的机制。MI-S 没有病毒杀伤作用，但抑制 HSV-1 和 HSV-2 的附着、渗透和细胞间传播，并降低 HSV-1 ICP27、UL42、gB 和 gD 蛋白的表达。MI-S 与阿昔洛韦也具有协同抗病毒作用。这些结果表明 MI-S 具有多种抗 HSV 作用模式。
