Чинарёв Александр Александрович


Младший научный сотрудник (Лаборатория углеводов)

Тел.: +7 (495) 330-03-00

Эл. почта: chinarev@carb.ibch.ru

Избранные публикации

  1. Bovin N.V., Tuzikov A.B., Chinarev A.A. (2008). Oligoglycines: Materials with unlimited potential for nanotechnologies. Nanotechnologies in Russia 3 (5-6), 48–61 ID:241
  2. Gambaryan A.S., Boravleva E.Y., Matrosovich T.Y., Matrosovich M.N., Klenk H.D., Moiseeva E.V., Tuzikov A.B., Chinarev A.A., Pazynina G.V., Bovin N.V. (2005). Polymer-bound 6' sialyl-N-acetyllactosamine protects mice infected by influenza virus. Antiviral Res. 68 (3), 116–23 [+]

    To develop a mouse model for testing receptor attachment inhibitors of human influenza viruses, the human clinical virus isolate in MDCK cells A/NIB/23/89M (H1N1) was adapted to mice by serial passaging through mouse lungs. The adaptation enhanced the viral pathogenicity for mice, but preserved the virus receptor binding phenotype, preferential binding to 2-6-linked sialic acid receptors and low affinity for 2-3-linked receptors. Sequencing of the HA gene of the mouse-adapted virus A/NIB/23/89-MA revealed a loss of the glycosylation sites in positions 94 and 163 of HA1 and substitutions 275Asp-->Gly in HA1 and 145Asn-->Asp in HA2. The four mouse strains tested differed significantly in their sensitivity to A/NIB/23/89-MA with the sensitivity increasing in the order of BALB/cJCitMoise, C57BL/6LacSto, CBA/CaLacSto and A/SnJCitMoise strains. Testing of protective efficacy of the polyacrylamide conjugate bearing Neu5Acalpha2-6Galbeta1-4GlcNAc trisaccharide under conditions of lethal or sublethal virus infection demonstrated a strong protective effect of this preparation. In particular, aerosol treatment of mice with the polymeric attachment inhibitor on 24-110 h after infection completely prevented mortality in sensitive animals and lessened disease symptoms in more resistant mouse strains.

    ID:238
  3. Bovin N.V., Tuzikov A.B., Chinarev A.A., Gambaryan A.S. (2004). Multimeric glycotherapeutics: new paradigm. Glycoconj. J. 21 (8-9), 471–8 [+]

    The general principle of anti-adhesion therapy is the inhibition of microorganism adhesion to the host cell with the help of a soluble receptor analog. Despite an evident attractiveness of the concept and its long existence, the therapeutics of the 'post-antibiotic era' have not yet appeared. This can be explained by the contradictoriness of requirements for anti-adhesion drugs: to be efficient a drug must be multivalent, i.e. large molecule, but to obtain FDA approval it should be a small molecule. A way to overcome this contradiction is self-assembly of glycopeptides. The carbohydrate part of glycopeptide is responsible for binding with the lectin of microorganisms, whereas a simple peptide part is responsible for an association to the so-called tectomers. Depending on the structure, tectomers are formed either spontaneously or upon promotion of a microorganism. In particular, sialopeptide, which is capable of converting to a tectomer only in the presence of the influenza virus, has been obtained. Thus, the new strategy of anti-adhesion therapy can be formulated as follows: (1) identification of oligosaccharide-receptor for a particular virus (bacteria); (2) optimization of the peptide part; (3) conventional trials. The expected advantages of this strategy are the following: (i) no polymer; (ii) a virion completely covered with a tectomer, i.e. blocking is both complete and irreversible; (iii) rapid and rational lead identification and optimization; (iv) minimum side effects; (v) potential for microorganism resistance to natural receptor is lower than in the case of mimetics.

    ID:240
  4. 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. (2003). Polyglycine II nanosheets: supramolecular antivirals? Chembiochem 4 (2-3), 147–54 [+]

    Tetraantennary peptides [glycine(n)-NHCH(2)](4)C can form stable noncovalent structures by self-assembly through intermolecular hydrogen bonding. The oligopeptide chains assemble as polyglycine II to yield submicron-sized, flat, one-molecule-thick sheets. Attachment of alpha-N-acetylneuraminic acid (Neu5Acalpha) to the terminal glycine residues gives rise to water-soluble assembled glycopeptides that are able to bind influenza virus multivalently and inhibit adhesion of the virus to cells 10(3)-fold more effectively than a monomeric glycoside of Neu5Acalpha. Another antiviral strategy based on virus-promoted assembly of the glycopeptides was also demonstrated. Consequently, the self-assembly principle offers new perspectives on the design of multivalent antivirals.

    ID:36