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
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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- "47. Kato, D.;Era, S.;Watanabe, I.;Arihara, M.;Sugiura, N.;Kimata, K.;Morita, KDENV Membrane (M) Protein with Activity Against Dengue Virus Infection.Chem. Biol. "
ABSTRACT: The dengue virus and related flaviviruses are an increasing global health threat. In this perspective, we comment and review medicinal chemistry efforts aimed at the prevention or treatment of dengue infections. We include target-based approaches aimed at viral or host factors, and results from phenotypic screenings at cellular assay systems for viral replication. This perspective is limited to the discussion of results that provide explicit chemistry, SAR, or appear to be of particular interest to the medicinal chemist for other reasons. The discovery and development efforts discussed here may at least partially be extrapolated towards other emerging flaviviral infections, such as West Nile virus. Therefore this perspective, although not specifically aimed at flaviviruses in general, should also be able to provide a general overview of the medicinal chemistry of these closely related infectious agents.
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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 . Studies demonstrated that fucoidan and chondroitin sulphate E has antiviral activity against DENV by direct binding of these compounds to the virus  . 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). "
ABSTRACT: Dengue represents a serious social and economic public health problem; then trying to contribute to improve its control, the objective of this research was to develop phytoterapics for dengue treatment using natural resources from Caatinga biome. Galactomannans isolated from Adenanthera pavonina L., Caesalpinia ferrea Mart., and Dimorphandra gardneriana Tull were chemically sulfated in order to evaluate the antioxidant, and antiviral activities and the role in the inhibition of virus DENV-2 in Vero cells. A positive correlation between the degree of sulfation, antioxidant and antiviral activities was observed. The sulfated galactomannans showed binding to the virus surface, indicating that they interact with DENV-2. The sulfated galactomannans from C. ferrea showed 96% inhibition of replication of DENV-2 followed by D. gardneriana (94%) and A. pavonina (77%) at 25 µg/mL and all sulfated galactomannans also showed antioxidant activity. This work is the first report of the antioxidant and antiviral effects of sulfated galactomannans against DENV-2. The results are very promising and suggest that these sulfated galactomannans from plants of Caatinga biome act in the early step of viral infection. Thus, sulfated galactomannans may act as an entry inhibitor of DENV-2.
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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) . 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. "
ABSTRACT: Dengue fever, a reemerging disease, is putting nearly 2.5 billion people at risk worldwide. The number of infections and the geographic extension of dengue fever infection have increased in the past decade. The disease is caused by the dengue virus, a flavivirus that uses mosquitos Aedes sp. as vectors. The disease has several clinical manifestations, from the mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, there is no approved drug for the treatment of dengue disease or an effective vaccine to fight the virus. Therefore, the search for antivirals against dengue virus is an active field of research. As new possible receptors and biological pathways of the virus biology are discovered, new strategies are being undertaken to identify possible antiviral molecules. Several groups of researchers have targeted the initial step in the infection as a potential approach to interfere with the virus. The viral entry process is mediated by viral proteins and cellular receptor molecules that end up in the endocytosis of the virion, the fusion of both membranes, and the release of viral RNA in the cytoplasm. This review provides an overview of the targets and progress that has been made in the quest for dengue virus entry inhibitors.
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