Isolation of an antiviral polysaccharide, nostoflan, from a terrestrial cyanobacterium, Nostoc flagelliforme.
A novel acidic polysaccharide, nostoflan, was isolated from a terrestrial cyanobacterium, Nostoc flagelliforme. Nostoflan exhibited a potent anti-herpes simplex virus type 1 (HSV-1) activity with a selectivity index (50% cytotoxic concentration/50% inhibitory concentration against viral replication) of 13,000. Sugar composition and methylation analyses revealed that it was 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. Two pyridylaminated oligosaccharides were prepared by partial acid hydrolysis and pyridylamination. On the basis of MALDI-TOF-MS and NMR analyses, they were found to be beta-D-Glcp-(1-->4)-D-Xyl-PA and beta-D-GlcAp-(1-->6)-beta-D-Glcp-(1-->4)-D-Gal-PA. From these results, nostoflan might be mainly composed of the following two types of sugar sequence: -->4)-beta-D-Glcp-(1-->4)-D-Xylp-(1--> and -->4)-[beta-D-GlcAp-(1-->6)-]-beta-D-Glcp-(1-->4)-D-Galp-(1-->. Besides anti-HSV-1 activity, nostoflan showed potent antiviral activities against HSV-2, human cytomegalovirus, and influenza A virus, but no activity against adenovirus and coxsackie virus was observed. Therefore, nostoflan has a broad antiviral spectrum against enveloped viruses whose cellular receptors are carbohydrates. Furthermore, nostoflan showed no antithrombin activity, unlike sulfated polysaccharides.
Kanekiyo
Kenji
K
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Lee
Jung-Bum
JB
Hayashi
Kyoko
K
Takenaka
Hiroyuki
H
Hayakawa
Yumiko
Y
Endo
Shunro
S
Hayashi
Toshimitsu
T
D000256:Adenoviridae / Q000187:drug effects; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003587:Cytomegalovirus / Q000187:drug effects; D004770:Enterovirus / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D046937:Nostoc / Q000737:chemistry*; D009975:Orthomyxoviridae / Q000187:drug effects; D011134:Polysaccharides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013917:Thrombin / Q000187:drug effects
D000998:Antiviral Agents; D011134:Polysaccharides; C502997:nostoflan; D013917:Thrombin