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Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
inhibitors of influenza virus adhesion

Since 1989 our laboratory studies hemagglutinin-mediated process of influenza virus reception on sialylated chains of the host cells. The aim of this study is the revealing of the fine mechanism and topography of the binding, particularities of the carbohydrate specificity of viral strains differing by point mutations, and, finally, the development of antiviral preparation acting by principle of inhibitor hemagglutinin-mediated adhesion by high affinity synthetic sialosides.
The most principal result is that oligosaccharide specificity of non-adapted (i.e. cultivated on animal cells MDCK) human strains is considerably different from the specificity of viruses grown on chicken embryos, i.e. that 6’-sialyllactoseamine (6’SLN) is a universal receptor capable to bind all the studied strains of both A and B (H1 and H3) types [ ]. This finding is essential for development of antivirals. The same was true for clinical material, i.e. viruses taken directly from patients. Highly sensitive assay method based on high m.w. PAA-conjugates was developed for this study (see above).
The further stage of antiviral development was the test of sialoconjugates in infectivity test on MDCK cell culture, also producing positive results. Finally, the tests on murine influenza model (see Fig. 3) displayed the efficiency of sialoconjugates containing 6’-SLN both in treatment (administration after infection) and prophylaxis (administration before or simultaneously with infection) regimens. Thus, the efficiency of anti-adhesion therapy on animal model was demonstrated for the first time.
The next stage of this program is the development and testing of antiadhesion therapeutics based on self-assembling glycopeptides (see Supramolecular chemistry).

 

Discovery of 6-Sulfo-3’SLN as specific receptor of H5N1 influenza viruses.

To characterize differences in the receptor-binding specificity of H5N1 chicken viruses and viruses of aquatic birds we used a panel of synthetic polyacrylamide-based sialylglycopolymers which carried identical terminal Neu5Acα2-3Gal fragments but varied by the structure of the next saccharide residues. H5N1 chicken and human viruses isolated in 1997 - 2005 bound sulfated trisaccharide Neu5Acα2-3Galβ1-4(6-HSO3)GlcNAcβ (6-Su-3`SLN) with the extraordinary high affinity. The binding of chicken and mammalian viruses to tracheal epithelial cells of green monkey decreased after treatment of cells with glucosamine-6-sulfatase suggesting the presence of 6-O-Su-3`SLN determinants in the airway epithelium. It remains to be seen whether existence of the 6-O-Su-3`SLN groups in the human airway epithelial cells might facilitate infection of humans with H5N1 chicken viruses.

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