Planta Med 2006; 72(2): 121-125
DOI: 10.1055/s-2005-373168
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Antiviral Activity of a Carrageenan from Gigartina skottsbergii against Intraperitoneal Murine Herpes simplex Virus Infection

C. A. Pujol1 , L. A. Scolaro1 , M. Ciancia2 , M. C. Matulewicz2 , A. S. Cerezo2 , E. B. Damonte1
  • 1Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
  • 2Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Further Information

Publication History

Received: January 12, 2005

Accepted: June 27, 2005

Publication Date:
10 November 2005 (online)

Abstract

The partially cyclized μ/ν-carrageenan 1C3, isolated from the red seaweed Gigartina skottsbergii, was previously shown to be a potent inhibitor of the in vitro replication of Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Here the protective effect of 1C3 in a murine model of intraperitoneal (i. p.) HSV-1 infection was evaluated. OF1 mice were i. p. infected with 5 × 105 PFU of HSV-1 KOS strain, and the effects of different treatments with 1C3 were studied. When 30 mg/kg of body weight of 1C3 was administered by the i. p. route immediately after HSV-1 infection, 87.5 % survival of the animals was achieved (p < 0.005), associated with a delay in the mean day of death in 1C3-treated non-surviving mice. Animal survival was not improved when multiple doses of 1C3 were also given in the period 1 - 48 h post-infection, and no protection was afforded when treatment was started after 24 h of infection. When virus and compound were injected by different routes, i. p. and intravenous (i. v.), respectively, a still significant protection was achieved (40 % survival, p < 0.05). No toxicity of 1C3 for the animals was recorded. The pharmacokinetic properties were analyzed after injection of 1C3 into the tail vein by monitoring of [3 H]-1C3 in plasma and organs and by a bioassay of the anti-HSV-1 activity remaining in serum after non-radioactive 1C3 inoculation. A very rapid disappearance of the compound from the blood was observed since only 5.9 - 0.9 % of the radioactivity of the initially administered [3 H]-1C3 appeared in the plasma between 5 - 300 minutes after administration. A transient peak of radioactivity was detected in the kidney 15 minutes after inoculation. The bioassay confirms the presence of the compound circulating in a biologically active form up to 1 hour after injection.

References

  • 1 Witvrouw M, De Clercq E. Sulfated polysaccharides extracted from sea algae as potential antiviral drugs.  Gen Pharmacol. 1997;  29 497-511
  • 2 Damonte E B, Matulewicz M C, Cerezo A S. Sulfated seaweed polysaccharides as antiviral agents.  Curr Med Chem. 2004;  11 2399-419
  • 3 Lüscher-Mattli M. Polyanions - a lost chance in the fight against HIV and other virus diseases?.  Antiviral Chem Chemother. 2000;  11 249-59
  • 4 Weiler B E, Schroder H C, Stefanovich V, Stewart D, Forrest J MS, Allen L B. et al . Sulphoevernan, a polyanionic polysaccharide, and the narcissus lectin potently inhibit human immunodeficiency virus infection by binding to viral envelope protein.  J Gen Virol. 1990;  71 1957-63
  • 5 Furusawa E, Furusawa S, Chou S C. Antileukemic activity of Viva-Natural, a dietary seaweed extract, on Rauscher murine leukemia in comparison with anti-HIV agents, azidothymidine, dextran sulfate and pentosan polysulfate.  Cancer Lett. 1991;  56 197-20
  • 6 Diringer H, Ehlers B. Chemoprophylaxis of scrapie in mice.  J Gen Virol. 1991;  I 72 457-60
  • 7 Hamasuna R, Eizuru Y, Shishime Y, Minamishima Y. Protective effect of carrageenan against murine cytomegalovirus infection in mice.  Antiviral Chem Chemother. 1993;  4 353-60
  • 8 Pancheva S N. Antiherpes effect of dextran sulphate combined with acyclovir in vitro and in vivo .  Antiviral Chem Chemother. 1993;  4 189-91
  • 9 Mathes L E, Hayes K A, Swenson C L, Polas P J, Weisbrode S E, Kociba G J. Evaluation of antiviral activity and toxicity of dextran sulfate in feline leukemia virus-infected cats.  Antimicrob Agents Chemother. 1991;  35 2147-50
  • 10 Offensperger W B, Offensperger S, Walter E, Blum H E, Gerok W. Sulfated polyanions do not inhibit duck hepatitis B virus infection.  Antimicrob Agents Chemother. 1991;  35 2431-3
  • 11 Zacharopoulos V R, Phillips D M. Vaginal formulations of carrageenan protect mice from Herpes simplex virus infection.  Clin Diagn Lab Immunol. 1997;  4 465-8
  • 12 Bourne K Z, Bourne N, Reising S F, Stanberry L R. Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2.  Antiviral Res. 1999;  42 219-26
  • 13 Coggins C, Blanchard K, Alvarez B, Brache V, Weisberg E, Kilmarx P H. et al . Preliminary safety and acceptability of a carrageenan gel for possible use as a vaginal microbicide.  Sex Trans Infect. 2000;  76 480-3
  • 14 Carlucci M J, Scolaro L A, Noseda M D, Cerezo A S, Damonte E B. Protective effect of a natural carrageenan on genital herpes simplex virus infection in mice.  Antiviral Res. 2004;  64 137-41
  • 15 Carlucci M J, Pujol C A, Ciancia M, Noseda M D, Matulewicz M C, Damonte E B. et al . Antiherpetic and anticoagulant properties of carrageenans from the red seaweed Gigartina skottsbergii and their cyclized derivatives: correlation between structure and biological activity.  Int J Biol Macromol. 1997;  20 97-105
  • 16 Carlucci M J, Scolaro L A, Damonte E B. Inhibitory action of natural carrageenans on Herpes simplex virus infection of mouse astrocytes.  Chemotherapy. 1999;  45 429-36
  • 17 Carlucci M J, Ciancia M, Matulewicz M C, Cerezo A S, Damonte E B. Antiherpetic activity and mode of action of natural carrageenans of diverse structural types.  Antiviral Res. 1999;  43 93-102
  • 18 Tal-Singer R, Peng C, Ponce de León M, Abrams W R, Banfield B W, Tufaro F. et al . Interaction of Herpes simplex virus glycoprotein gC with mammalian cell surface molecules.  J Virol. 1995;  69 4471-83
  • 19 Matulewicz M C, Ciancia M, Noseda M D, Cerezo A S. Carrageenan systems from tetrasporic and cystocarpic stages of Gigartina skottsbergii .  Phytochemistry. 1989;  28 2937-41
  • 20 Ciancia M, Matulewicz M C, Finch P, Cerezo A S. Determination of the structures of cystocarpic carrageenans from Gigartina skottsbergii by methylation analysis and NMR spectroscopy.  Carbohydr Res. 1993;  238 241-8
  • 21 Couto A S, Gonçalves M F, Colli W, de Lederkremer R M. The N-linked carbohydrate chain of the 85-kilodalton glycoprotein from Trypanosoma cruzi trypomastigotes contains sialyl, fucosyl and galactosyl(α-1 - 3)galactose units.  Mol Biochem Parasitol. 1990;  39 101-8
  • 22 Hartman N R, Johns D G, Mitsuya H. Pharmacokinetic analysis of dextran sulfate in rats as pertains to its clinical usefulness for therapy of HIV infection.  AIDS Res Hum Retroviruses. 1990;  6 805-12
  • 23 Hayashi K, Hayashi T, Kojima I. A natural sulfated polysaccharide, calcium spirulan, isolated from Spirulina platensis: in vitro and ex vivo evaluation of anti-Herpes simplex virus and anti-human immunodeficiency virus activities.  AIDS Res Hum Retroviruses. 1996;  12 1463-71
  • 24 Nakashima H, Yoshida O, Baba M, De Clercq E, Yamamoto N. Anti-HIV activity of dextran sulphate as determined under different experimental conditions.  Antiviral Res. 1989;  11 233-46
  • 25 Guimaraes M AM, Mourao P AS. Urinary excretion of sulfated polysaccharides administered to Wistar rats suggest a renal permselectivity to these polymers based on molecular size.  Biochim Biophys Acta. 1997;  1335 161-72
  • 26 Ni L, Boudinot F D, Boudinot S G, Henson G W, Bossard G E, Martellucci S A. et al . Pharmacokinetics of antiviral polyoxometalates in rats.  Antimicrob Agents Chemother. 1994;  38 504-10

Carlos Alberto Pujol

Laboratorio de Virología

Departamento de Química Biológica

Facultad de Ciencias Exactas y Naturales

Universidad de Buenos Aires

Pabellón 2

Piso 4

Ciudad Universitaria

C1428BGA Buenos Aires

Argentina

Phone: +54-11-4576-3334

Fax: +54-11-4576-3342

Email: capujol@qb.fcen.uba.ar