Chemoenzymatic synthesis of neuraminic acid analogs structurally varied at C-5 and C-9 as potential inhibitors of the sialidase from influenza virus

Neuraminidase-treated erythrocytes coated with a variety of neuraminic acid-containing glycoproteins adsorbed influenza virus and neuraminidase-free hemagglutinins, but not purified neuraminidase. The results indicate that neuraminic acid is the binding site on the glycoprotein and that the rest of the molecule does not play a specific role in the reaction.

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Mesoionic Heterocyclic Compounds as Candidate Messenger RNA Cap Analogue Inhibitors of the Influenza Virus RNA Polymerase Cap-Binding Activity

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632020901900504 ◽

2009 ◽

Vol 19 (5) ◽

pp. 213-218 ◽

Cited By ~ 6

Author(s):

Ian Mickleburgh ◽

Feng Geng ◽

Laurence Tiley

Keyword(s):

Influenza Virus ◽

Rna Polymerase ◽

Messenger Rna ◽

Binding Activity ◽

Endonucleolytic Cleavage ◽

Virus Rna ◽

Fused Ring ◽

Mesoionic Heterocycles ◽

Potential Inhibitors

Background: An unusual feature of influenza viral messenger RNA (mRNA) synthesis is its dependence upon host cell mRNAs as a source of capped RNA primers. A crucial activity of the influenza polymerase is to steal these primers by binding and cleaving the caps from host mRNAs. The recent structural analysis of the cap-binding fragment of the influenza virus PB2 protein has highlighted the importance of the mesoionic properties of the N7-methylguanine (N7mG) component of the mRNA cap in this interaction. Methods: A series of mesoionic heterocycles with 5,6-fused ring systems analogous to the N7mG component of mRNA cap structures were synthesized and examined for the ability to inhibit the cap-binding activity of the influenza virus RNA polymerase complex using a bead-based in vitro cap-binding assay. Results: None of the compounds tested were able to significantly inhibit binding and subsequent endonucleolytic cleavage of a synthetic radiolabelled capped mRNA substrate by recombinant influenza virus polymerase in vitro. Conclusions: Compounds analogous to the mesoionic N7mG component of mRNA cap structures comprise a large class of potential inhibitors of the influenza virus polymerase. Although this preliminary assessment of a small group of related analogues was unsuccessful, further screening of this class of compounds is warranted.

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Prediction of selective inhibition of neuraminidase from various influenza virus strains by potential inhibitors

Biochemistry (Moscow) Supplement Series B Biomedical Chemistry ◽

10.1134/s1990750817020044 ◽

2017 ◽

Vol 11 (2) ◽

pp. 166-185

Author(s):

A. V. Mikurova ◽

A. V. Rybina ◽

V. S. Skvortsov

Keyword(s):

Influenza Virus ◽

Selective Inhibition ◽

Potential Inhibitors ◽

Virus Strains

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Chemoenzymatic synthesis and application of a sialoglycopolymer with a chitosan backbone as a potent inhibitor of human influenza virus hemagglutination

Carbohydrate Research ◽

10.1016/j.carres.2006.04.024 ◽

2006 ◽

Vol 341 (11) ◽

pp. 1803-1808 ◽

Cited By ~ 36

Author(s):

Yutaka Makimura ◽

Shinya Watanabe ◽

Takashi Suzuki ◽

Yasuo Suzuki ◽

Hideharu Ishida ◽

...

Keyword(s):

Influenza Virus ◽

Potent Inhibitor ◽

Chemoenzymatic Synthesis ◽

Human Influenza ◽

Human Influenza Virus

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Prediction of selective inhibition of neuraminidase from various influenza virus strains by potential inhibitors

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20166206691 ◽

2016 ◽

Vol 62 (6) ◽

pp. 691-703 ◽

Cited By ~ 6

Author(s):

A.V. Mikurova ◽

A.V. Rybina ◽

V.S. Skvortsov

Keyword(s):

Influenza Virus ◽

3D Structure ◽

Selective Inhibition ◽

Regression Equations ◽

Independent Variables ◽

3D Data ◽

Ic50 Values ◽

Potential Inhibitors ◽

Virus Strains ◽

Selection Of

A universal model of inhibition of neuraminidases from various influenza virus strains by a particular has been developed. It is based on known 3D data for neuraminidases from three influenza virus strains (A/Tokyo/3/67, A/tern/Australia/G70C/75, B/Lee/40) and modeling of 3D structure of neuraminidases from other strains (A/PR/8/34 and A/Aichi/2/68). Using docking and molecular dynamics, we have modeled 235 enzyme-ligand complexes for 185 compounds with known IC50 values. Selection of final variants among three results obtained for each enzyme-ligand pair and calculation of independent variables for generation of linear regression equations was performed using MM-PBSA/MM-GBSA. This resulted in the set of equations individual strains and the equations pooling all the data. Thus using this approach it is possible to predict inhibition for neuraminidase from each of the considered strains by a particular inhibitor and to predict the range of its action on neuraminidases from various influenza virus strains.

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