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-Glqp-(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 β-D-Glcp-(1→4)-D-Xyl-PA and β-D-GlcAp-(1→6)-β-D-Glcp-(1-4)-D-Gal-PA. From these results, nostoflan might be mainly composed of the following two types of sugar sequence: →4)-β-D-Glcp-(1→4)-D-Xylp-(1→ and →4)-[β-D-GlcAp- (1→6)-]-β-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.