Structure and anti-Dengue virus activity of sulfated polysaccharide from a marine alga

Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, Global COE Program for Innovation in Human Health Sciences, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 09/2008; 376(1):91-5. DOI: 10.1016/j.bbrc.2008.08.100
Source: PubMed


A sulfated polysaccharide, named fucoidan, from the marine alga Cladosiphon okamuranus is comprised of carbohydrate units containing glucuronic acid and sulfated fucose residues. Here we found this compound potently inhibits dengue virus type 2 (DEN2) infection. Viral infection was inhibited when DEN2, but not other serotypes, was pretreated with fucoidan. A carboxy-reduced fucoidan derivative in which glucuronic acid was converted to glucose did not inhibit viral infection. Elimination of the sulfated function group from fucoidan significantly attenuated the inhibitory activity on DEN2 infection with <1% fucoidan. DEN2 particles bound exclusively to fucoidan, indicating that fucoidan interacts directly with envelope glycoprotein (EGP) on DEN2. Structure-based analysis suggested that Arg323 of DEN2 EGP, which is conformationally proximal to one of the putative heparin binding residues, Lys310, is critical for the interaction with fucoidan. In conclusion, both the sulfated group and glucuronic acid of fucoidan account for the inhibition of DEN2 infection.

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    • "The use of entrance inhibitor in enveloped viruses is a very attractive strategy for therapeutic intervention, as the site of action of the inhibitor is likely to be extracellular and therefore relatively accessible, and this could also limit cell toxicity [48]. Studies demonstrated that fucoidan and chondroitin sulphate E has antiviral activity against DENV by direct binding of these compounds to the virus [8] [9]. This study showed that DENV-2 bound to SGAP, SGDG, and SGCF (Figure 2), and this binding may be responsible for the inhibitory activity of sulfated galactomannans (Figure 3). "
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    Evidence-based Complementary and Alternative Medicine 08/2015; 2015(3):591214. DOI:10.1155/2015/591214 · 1.88 Impact Factor
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    • "Similarly, cellular receptor molecules that interact with domain III may also have antiviral activity. One such molecule, the sulfated polysaccharide fucoidan, blocks DENV-2 virus entry into target cells by binding to E glycoprotein domain III and competing with the cellular receptors (IC50: 4.7 μg/mL) [99]. The high molecular weight compound curdlan sulfate (CRDS) is a sulfated polysaccharide with branched β-d-(1→3) glucan backbone and piperidine-N-sulfonic acid groups. "
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    BioMed Research International 07/2014; 2014:825039. DOI:10.1155/2014/825039 · 1.58 Impact Factor
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    • "There are four distinct serotypes, DENV-1, DENV-2, DENV-3, and DENV-4. Dengue virus can cause a range of diseases from asymptomatic infection to mild dengue fever (DF) or severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS)12. DENV is transmitted principally in a cycle that involves humans and mosquito vectors, Aedes aegypti and Aedes albopictus. "
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