Kanekiyo Kenji, Hayashi Kyoko, Lee Jung-Bum, Takenaka Hiroyuki, Hayashi Toshimitsu
Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama City, Japan.
Yakugaku Zasshi. 2008 May;128(5):725-31. doi: 10.1248/yakushi.128.725.
Recently, the development of antiviral agents with novel mechanisms of action has been required since many types of infectious disease have become a serious problem in our society. In the present study, we isolated a novel acidic polysaccharide, nostoflan (NSF), from a terrestrial blue-green alga, Nostoc flagelliforme, and examined its structure and antiviral activity. The sugar composition and methylation analyses of NSF revealed that it is mainly composed of (-->4)- D-Glcp-(1-->, -->6,4)-D-Glcp-(1-->, -->4)-D-Galp-(1-->, -->4)-D-Xylp-(1-->, D-GlcAp-(1-->, D-Manp-(1-->) with a ratio of ca. 1:1:1:1:0.8:0.2. Oligosaccharide analysis after partial acid hydrolysis of NSF revealed that this polysaccharide might be mainly composed of the sugar sequences of (-->4)-beta-D-Glcp-(1-->4)-D-Xylp-(1 and-->4)-[beta-D-GlcAp-(1-->6)-]-beta-D-Glcp-(1-->4)-D-Galp-(1-->). NSF showed potent antiviral activities against several enveloped viruses including herpes simplex virus type 1, type 2 (HSV-1, HSV-2), human cytomegalovirus, and influenza A virus (IFV). NSF selectively inhibited the attachment of HSV-1 to host cells but not its penetration phase. In an experimental animal study where IFV-infected mice received NSF intranasally, the mortality of mice was significantly decreased. Neutralizing titers in sera of mice treated with NSF were higher than in those treated with oseltamivir. From these results, NSF was found to be a novel polysaccharide that shows antiviral activity in vitro and in vivo in spite of a nonsulfated polysaccharide.
近年来,由于多种传染病已成为社会的严重问题,因此需要开发具有新型作用机制的抗病毒药物。在本研究中,我们从陆生蓝藻发菜中分离出一种新型酸性多糖,即发菜聚糖(NSF),并对其结构和抗病毒活性进行了研究。NSF的糖组成和甲基化分析表明,它主要由(→4)-D-葡萄糖-(1→)、(→6,4)-D-葡萄糖-(1→)、(→4)-D-半乳糖-(1→)、(→4)-D-木糖-(1→)、D-葡萄糖醛酸-(1→)、D-甘露糖-(1→)组成,比例约为1:1:1:1:0.8:0.2。NSF部分酸水解后的寡糖分析表明,该多糖可能主要由(→4)-β-D-葡萄糖-(1→4)-D-木糖-(1和→4)-[β-D-葡萄糖醛酸-(1→6)-]-β-D-葡萄糖-(1→4)-D-半乳糖-(1→)的糖序列组成。NSF对包括单纯疱疹病毒1型、2型(HSV-1、HSV-2)、人巨细胞病毒和甲型流感病毒(IFV)在内的多种包膜病毒具有强大的抗病毒活性。NSF选择性地抑制HSV-1与宿主细胞的附着,但不抑制其穿透阶段。在IFV感染小鼠经鼻给予NSF的实验动物研究中,小鼠的死亡率显著降低。用NSF治疗的小鼠血清中的中和效价比用奥司他韦治疗的小鼠更高。从这些结果中发现,NSF是一种新型多糖,尽管它是一种非硫酸化多糖,但在体外和体内均表现出抗病毒活性。