Neuraminidase inhibition

Hagiwara T, Kijima-Suda I, Ido T, Ohrui H, Tomita K (1994) Inhibition of bacterial and viral sialidases by 3-fluoro-V-acetyIneuraminic acid, Carbohydr Res 263 167-172 Haskell TH, Peterson FE, Watson D, Plessas NR, Culbertson T (1970) Neuraminidase inhibition and viral chemotherapy, J Med Chem 13 697-704 Hatakeyama S, Sugaya N, Ito M, Yamazaki M, Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y (2007) Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors, JAMA 297 1435-1442 Hay AJ (1992) The action of adamantanamines against influenza A viruses inhibition of the M2 ion channel protein, Semin Virol 3 21-30... 

Bacterial neuraminidase inhibits the formation of O by PMNs challenged with latex particles or with Con A, suggesting an essential sialic acid in these receptors Treatment with neuraminidase also caused PMNs to form less H2O2 in response to Staph, aureus and to kill fewer of the bacteria The blockade of the effects on Con A... 

Influenza neuraminidase Inhibition and plaque reduction by carbocyclic analogues... 

Karasuno, T., Kanayama, Y, Nishiura, T., Nakao, H., Yonezawa, T., and Tarui, S., 1992, Gly-cosidase inhibitors (castanospermine and swainsonine) and neuraminidase inhibit pokeweed mitogen-induced B cell maturation. Ear. J. Immunol. 22 2003-2008. 

It may be noted, in connection with neuraminidase inhibition, that the a-ketosidic configuration is not always a requirement for such behavior since the 2,3-unsaturated derivative (XXXV) was a potent... 

Figure 6.5 Neuraminidase inhibition activity of developed glycosyl triazoles.

An overview of the role of the virus-associated glycoprotein sialidase (neuraminidase) and some of the most recent developments towards the discovery of anti-influenza drugs based on the inhibition of influenza virus sialidase is provided in this chapter. 

Viral replication, packaging and release. Drug Disc Today 1 388-397 Meindl P, Tuppy H (1969) 2-Deoxy-2,3-dehydrosialic acids. II. Competitive inhibition of Vibrio cholerae neuraminidase by 2-deoxy-2,3-dehydro-V-acyIneuraminic acids. Hoppe-Seyler s Z Physiol Chem 350 1088-1092... 

Palese P, Tobita K, Ueda M, Compans RW (1974b) Characterization of temperature sensitive influenza virus mutants defective in neuraminidase. Virology 61 397 10 Pegg MS, von Itzstein M (1994) Slow-binding inhibition of sialidase from influenza virus, Biochem Mol Biol Int 32 851-858... 

Ryan DM, Ticehurst J, Dempsey M, Penn CR (1994) Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-iV-acetylneuraminic add) is consistent with extracellular actiivity of viral neuraminidase (sialidase), Antimicrob Agents Chemother 10 2270-2275... 

The influenza virus possesses a neuraminidase that plays a key role in elution of newly synthesized progeny from infected cells. If this process is inhibited, spread of the vims is markedly diminished. Inhibitors of this enzyme are now available for use in treating patients with influenza. 

Viruses don t have a reproductive system of their own and need to take over healthy cells by puncturing them with tiny spikes called hemagglutinin so that they can use the cells reproductive mechanism to make more viruses. These viral spikes are coated with an enzyme called neuraminidase, which helps to break down cellular walls. Flavonoids that occur in elderberries inhibit viral action and thereby improve immune response. It is thought that the flavoniods may also inhibit the action of neuraminidase. 

Simple imine formation was used in the formation of large DCLs directed toward inhibition of the enzyme neuraminidase by Eliseev and coworkers [11]. Neuraminidase is involved in the propagation of the influenza virus... 

Pharmacology The proposed mechanism of action of zanamivir is via inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release. 

Zanamivir (2) is a potent competitive inhibitor of viral neuraminidase glycoprotein, which is essential in the infective cycle of both influenza A and B viruses. It inhibits a wide range of influenza A and B types in vitro as well as in vivo. The concentrations of inhibiting in vitro plaque formation of influenza A and B virus by 50% in Madin-Darby canine kidney (MDCK) cells were 0.004-0.014 p.mol/L in laboratory-passaged strains, and 0.002-16 p.mol/L in assays of clinical isolates. Due to its low bioavailability, it is delivered by inhalation via the Diskhaler , 10 mg twice daily, or intranasally 2-4 times daily for 5 days. After an intravenous dose of 1 -16 mg, the median elimination half-life was ti/2 = 7 h, the volume of distribution at steady state was Vdss = 16 L, and 90% of the dose was excreted unchanged in the urine. After intranasal and inhaled (dry powder) administration, maximum serum concentrations occurred within 2h and the terminal phase half-lives were 3.4 and 2.9 h, respectively. The bioavailabilities were 10 and 25%, respectively, and 20% after inhalation of zanamivir (2) by nebulizer. 

Zanamivir (Relenza) is a neuraminidase inhibitor with activity against influenza A and B strains. Like oseltamivir, zanamivir is a reversible competitive antagonist of viral neuraminidase. It inhibits the release of progeny virus, causes viral aggregation at the cell surface, and impairs viral movement through respiratory secretions. Resistant variants with hemagglutinin and/or neuraminidase mutations have been produced in vivo however, clinical resistance to zanamivir is quite rare at present. 

A. Oseltamivir inhibits neuraminidase, an enzyme that cleaves neuraminic acid from oligosaccharides. Neuraminidase activity aids the movement of viral particles through neuraminic acid-rich respiratory secretions and is required for the release of progeny virions. Inhibition of viral DNA polymerase is the mechanism of action of nucleoside analogue antiviral drugs. Interferons do stimulate the JAK-STAT signaling pathway but do not stimulate proliferation of immune cells. Ribavirin inhibits GTP synthesis, and the antiretroviral protease inhibitors (e.g., ritonavir) inhibit HIV protease. 

Siastatin B (40), the first natural inhibitor of neuraminidase and a compound that also inhibits -D-glucuronidase, was discovered in 1974 [139]. Two total syntheses of this compound have been published to date [140,141]. Due to the fact that recent studies have shown that human tumours are associated with... 

Mechanism of Action An antiviral that appears to inhibit the influenza virus enzyme neuraminidase, which is essential for viral replication. Therapeutic Effect Prevents viral release from infected cells. 

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