An Algal-Derived DL-Galactan Hybrid is an Efficient Preventing Agent for in vitro Dengue Virus Infection

Abstract

The DL-galactan hybrid C2S-3, isolated from the red seaweed Cryptonemia crenulata (Halymeniaceae, Halymeniales), is a potent and selective inhibitor of the multiplication of diverse strains of DENV-2 in Vero cells with higher effectiveness than the reference polysaccharide heparin. The presence of the compound either only at virus adsorption or at virus internalization exerted a significant and dose-dependent inhibition in DENV-2 plaque number. The compound failed to inactivate DENV-2 directly by incubation of virus before cell infection as well as to induce a refractory state by cell pretreatment. Thus, the inhibitory effect was exclusively exerted through a blockade in virus multiplication during the infectious process. When the entry of DENV-2 particles into the cell is bypassed, as occurs in virus RNA transfection, the polysaccharide C2S-3 failed to block the completion of the multiplication cycle. Furthermore, the antiviral properties of C2S-3 are not correlated with anticoagulant activity.

Key words

Antiviral agent - dengue virus - sulfated galactan - marine alga - Cryptonemia crenulata - Halymeniaceae

References

• 1 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.
• 2 Schols D. HIV co-receptor inhibitors as novel class of anti-HIV drugs.  Antivir Res. 2006;  71 216-26.
• 3 Gubler D J. Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century.  Trends Microbiol. 2002;  10 100-3.
• 4 Chen Y, Maguire T, Hileman R E, Fromm J R, Esko J D, Linhardt R J. et al . Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate.  Nat Med. 1997;  3 866-71.
• 5 Damonte E B, Pujol C A, Coto C E. Prospects for the therapy and prevention of dengue virus infections.  Adv Virus Res. 2004;  63 239-85.
• 6 de S.F-Tischer P C, Talarico L B, Noseda M D, Guimaraes S MPB, Damonte E B, Duarte M ER. Chemical structure and antiviral activity of carrageenans from Meristiella gelidium against Herpes simplex and dengue virus.  Carbohydr Polym. 2006;  63 459-65.
• 7 Lee E, Pavy M, Young N, Freeman C, Lobigs M. Antiviral effect of the heparan sulfate mimetic, PI-88, against dengue and encephalitic flaviviruses.  Antivir Res. 2006;  69 31-8.
• 8 Talarico L B, Damonte E B. Interference in dengue virus adsorption and uncoating by carrageenans.  Virology. 2007;  363 473-85.
• 9 Talarico L B, Pujol C A, Zibetti R GM, Faría P CS, Noseda M D, Duarte M ER. et al . The antiviral activity of sulfated polysaccharides against dengue virus is dependent on virus serotype and host cell.  Antivir Res. 2005;  66 103-10.
• 10 Talarico L B, Zibetti R GM, Faría P CS, Scolaro L A, Duarte M ER, Noseda M D. et al . Anti-Herpes simplex virus activity of sulfated galactans from the red seaweeds Gymnogongrus griffithsiae and Cryptonemia crenulata .  Int J Biol Macromol. 2004;  34 63-71.
• 11 Zibetti R GM, Noseda M D, Cerezo A S, Duarte M ER. The system of galactans from Cryptonemia crenulata (Halymeniaceae, Halymeniales) and the structure of two major fractions. Kinetic studies on the alkaline cyclization of the unusual diad G2S→D(L)6S.  Carbohydr Res. 2005;  340 711-22.
• 12 Feyzi E, Trybala E, Bergström T, Lindahl U, Spillmann D. Structural requirement of heparan sulfate for interaction with Herpes simplex virus type 1 virions and isolated glycoprotein C.  J Biol Chem. 1997;  272 24 850-57.
• 13 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;  56 197-205.
• 14 Pujol C A, Scolaro L A, Ciancia M, Matulewicz M C, Cerezo A S, Damonte E B. Antiviral activity of a carrageenan from Gigartina skottsbergii against intraperitoneal murine Herpes simplex virus infection.  Planta Med. 2006;  72 121-5.
• 15 Hamasuna R, Eizuru I, Shishime Y, Minamishima Y. Protective effect of carrageenan against murine cytomegalovirus infection in mice.  Antiviral Chem Chemother. 1993;  4 353-60.
• 16 Ono L, Wollinger W, Rocco I M, Coimbra T LM, Gorin P AJ, Sierakowski M R. In vitro and in vivo antiviral properties of sulphated galactomannans against yellow fever virus (BeH111 strain) and dengue 1 virus (Hawaii strain).  Antivir Res. 2003;  60 201-8.