The general principle of influenza anti-adhesion therapy is the blocking of attachment of virus to host cell. The attachment is mediated by the interaction of the virus hemagglutinin (HA) with Neu5Aca2-6Galb1-4GlcNAc (6’SLN)-containing glycoconjugates. We developed supramolecular assemblies as specific blockers of viral HA, better to say, blockers of virus particles [1]. Here we present biantennary oligoglycines of general formula R-Glyn-Х-Glyn-R (R=H, 6’SLN; X=-HN-(СН2)m-NH-, m=2, 4, 10; n=1–7) with two pendant sialoligands. According to atomic force microscopy (AFM) data the peptides and glycopeptides form submicron-sized, one-molecule thick aggregates, which can be considered as two-dimensional crystals. Oligoglycine chains take the so-called polyglycine II conformation [2]. The found properties of biantennary glycines differ from those of the corresponding (synthesized earlier) tri- and tetra-antennary molecules. The antiviral activity of glycopeptides was studied in fetuin binding inhibition assay. All the assembling glycopeptides demonstrated antiviral activity up to 50 times higher than the activity of monomeric 6’SLN.
Two mechanisms of inhibition of influenza virus are discussed. The first is formation of supramolecular envelope around a virus particle. The second is competition of glycopeptides with sialic receptors for hemagglutinin.
[1] Tuzikov A.B., Chinarev A.A., Gambaryan A.S., Oleinikov V.A., Klinov D.V., Matsko N.B., Kadykov V.A., Ermishov M.A., Demin I.V., Demin V.V., Rye P.D., Bovin N.V. Polyglycine II nanosheets: Supramolecular antivirals? ChemBioChem, 2003, 4, 147-154.
[2] Tsygankova S.V., Chinarev A.A., Tuzikov A.B., Zaitsev I.S., Severin N., Kalachev A.A., Rabe J.P., Bovin N.V., Assembly of oligoglycine layers on mica surface. Journal of Biomaterials and Nanobiotechnology, 2011, 2, 91–97.
