Article

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: 2.48). 09/2008; 376(1):91-5. DOI:10.1016/j.bbrc.2008.08.100 pp.91-5
Source: PubMed

ABSTRACT 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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Keywords

carboxy-reduced fucoidan derivative
 
compound potently inhibits dengue virus type 2
 
conformationally proximal
 
envelope glycoprotein
 
fucoidan
 
fucoidan account
 
fucoidan interacts
 
glucuronic acid
 
inhibition
 
marine alga Cladosiphon okamuranus
 
putative heparin binding residues
 
serotypes
 
sulfated fucose residues
 
sulfated function group
 
sulfated group
 
sulfated polysaccharide
 
Viral infection