Antiherpetic Activities of Sulfated Polysaccharides from Green Algae

Abstract

In order to evaluate the potency of novel antiviral drugs, 11 natural sulfated polysaccharides (SPs) from 10 green algae (Enteromorpha compressa, Monostroma nitidum, Caulerpa brachypus, C. okamurai, C. scapelliformis, Chaetomorpha crassa, C. spiralis, Codium adhaerens, C. fragille, and C. latum) and 4 synthetic sulfated xylans (SXs) prepared from the β-(1,3)-xylan of C. brachypus, were assayed for anti-Herpes simplex virus type 1 (HSV-1) activity. Except for one from E. compressa, all SPs showed potent anti-HSV-1 activities with 50 % inhibitory concentrations (IC₅₀) of 0.38 - 8.5 μg/mL, while having low cytotoxicities with 50 % inhibitory concentrations of >2900 μg/mL. Anti-HSV-1 activities of SXs were dependent on their degrees of sulfation. To delineate the drug-sensitive phase, 4 polysaccharides, which showed potent anti-HSV-1 activities, were applied to time-of-addition experiments. Among the polysaccharides tested, 3 polysaccharides (SX4, SP4 from C. brachypus, and SP11 from C. latum) showed strong anti-HSV-1 activities with IC₅₀ of 6.0, 7.5, and 6.9 μg/mL, respectively, even when added to the medium 8 h post-infection. These experiments demonstrated that some sulfated polysaccharides not only inhibited the early stages of HSV-1 replication, such as virus binding to and penetration into host cells, but also interfered with late steps of virus replication. These results revealed that some sulfated polysaccharides from green algae should be promising candidates of antiviral agents which might act on different stages in the virus replication cycle.

Sulfated polysaccharides - Herpes simplex virus type 1 (HSV-1) - Chlorophyta (green algae) - Ulvophyceae - antiviral activity

References

• 1 Elion G B, Furman P A, Fyfe J A, De Mirouds P, Beauchamp L, Schaeffer H J. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine.  Proc Natl Acad Sci USA. 1977;  74 5716-20
• 2 Hayashi K, Hamada J, Hayashi T. A screening strategy for selection of anti-HSV-1 and anti-HIV extracts from algae.  Phytother Res. 1996;  10 233-7
• 3 Hoshino T, Hayashi T, Hayashi K, Hamada J, Lee J B, Sankawa U. An antivirally active sulfated polysaccharide from Sargassum horneri (Turner) C. Agardh.  Biol Pharm Bull. 1998;  21 730-4
• 4 Witvrouw M, Desmyter J, De Clercq E. Antiviral portrait series: 4. Polysulfates as inhibitors of HIV and other enveloped viruses.  Antiviral Chem Chemother. 1994;  5 345-59
• 5 Witvrouw M, De Clercq E. Sulfated polysaccharides extracted from sea algae as potential antiviral drugs.  Gen Pharmacol. 1997;  29 497-511
• 6 Béress A, Wassermann O, Bruhn T, Béress L. A new procedure for the isolation of anti-HIV compounds (polysaccharides and polyphenols) from the marine alga Fucus vesiculosus .  J Nat Prod. 1993;  56 478-88
• 7 Carlucci M J, Scolaro L A, Errea M I, Maltulewicz M C, Damonte E B. Antiviral activity of natural sulfated galactans on herpes virus multiplication in cell culture.  Planta Medica. 1997;  63 429-32
• 8 Kolender A A, Pujol C A, Damonte E B, Maltulewicz M C, Cerezo A S. The system of sulfated α-(1→3)-linked D-mannans from the red seaweed Nothogenia fastigiata: structures, antiherpetic and anticoagulant properties.  Carbohydr Res. 1997;  304 53-60
• 9 Yamagaki T, Maeda M, Kanazawa K, Ishizuka Y, Nakanishi H. Structural clarification of Caulerpa cell wall β-1,3-xylan by NMR spectroscopy.  Biosci Biotech Biochem. 1997;  60 1222-8
• 10 Maeda M, Uehara T, Harada N, Sekiguchi M, Hiraoka A. Heparinoid-active sulphated polysaccharides from Monostroma nitidum and their distribution in the Chlorophyta.  Phytochemistry. 1991;  30 3611-4
• 11 Uehara T, Takeshita M, Maeda M. Studies on anticoagulant-active arabinan sulfates from the green alga, Codium latum .  Carbohydr Res. 1992;  235 309-11
• 12 Imanari T, Arakawa , Tamura Z. Gas chromatographic analysis of aldoses.  Chem Pharm Bull. 1967;  17 196-9
• 13 Lee J B, Yamagaki T, Maeda M, Nakanishi H. Rhamnan sulfate from cell walls of Monostroma latissimum .  Phytochemistry. 1998;  41 921-5
• 14 Takano R, Yoshikawa S, Ueda T, Hayashi K, Hirase S, Hara S. Sulfation of polysaccharides with sulfuric acid mediated by dicyclohexylcarbodiimide.  J Carbohydr Chem. 1996;  15 449-57
• 15 Ivanova V, Rouseva R, Kolarova M, Serkedjieva J, Rachev R, Manolova N. Isolation of a polysaccharide with antiviral effect from Ulva lactuca .  Prep Biochem. 1994;  24 83-97
• 16 Yoshida T, Yasuda Y, Mimura T, Kaneko Y, Nakashima H, Yamamoto N, Uryu T. Synthesis of curdlan sulfates having inhibitory effects in vitro against AIDS viruses HIV-1 and HIV-2.  Carbohydr Res. 1995;  276 425-36
• 17 Honess R W, Roizman B. Regulation of herpes virus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins.  J Virol. 1974;  14 8-19
• 18 Roizman B, Sears A E. Herpes Simplex Viruses and Their Replication. In: Fields BN, Knipe DM, Howley PM, editors Philadelphia; Lippincott-Raven Publishers 1996: pp 2231-95
• 19 Palu G, Biasolo M A, Sartor G, Massoti L, Pappini E, Floreani M, Palatini P. Effects of herpes virus type I infection on the plasma membrane and related functions of HeLa S3 cells.  J Gen Virol. 1994;  75 3337-44
• 20 Lee J B, Hayashi K, Hayashi T, Sankawa U. Antiviral activities against HSV-1, HCMV, and HIV-1 of rhamnan sulfate from Monostroma latissimum .  Planta Medica. 1999;  65 439-41