Neuraminidase enzyme mechanism

The author would like to acknowledge Peter Colman, my collaborator in neuraminidase crystallography, Mike Lawrence for the GRID maps shown here and reading this manuscript, Brian Smith for discussions on enzyme mechanisms, Jenny McKimm-Breschkin for discussions on drug resistance, Bert van Donkelaar for technical support, and Paul Davis for computing support. 

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. 

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. 

Mechanism of Action A selective inhibitor of influenza virus neuraminidase, an enzyme essential for viral replication. Acts against both influenza A and B viruses. Therapeutic Effect Suppresses the spread of infect ion within the respiratory system and re-duces the duration of clinical symptoms. 

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. 

Transition state mimics have generally been synthesized first on an empirical basis tetrahedral analogues if the mechanism involves a tetrahedral intermediate planar analogues if the enzyme catalyses an SNl displacement, as exemplified by the synthesis of DANA (71) for the inhibition of neuraminidase. Recognition that transition state geometry and... 

Mechanism of Action. Oseltamivir and zanamivir inhibit a specific enzyme (neuraminidase) that the influenza virus uses to complete its biosynthesis and release. By inhibiting this enzyme, these drugs impair a key step in viral replication, and reduce the ability of the virus to infect other respiratory cells. 

The exact mechanism of enzyme catalysis as well as the structural and energetic aspects of substrate and inhibitor binding have been studied with the aid of molecular modeling, based on the complex of Neu5Ac with influenza virus A/Tokyo/3/67 neuraminidase (Scheme 16.4) [74c]. 

Mechanisms These drugs are inhibitors of neuraminidase produced by influenza A and B. This viral enzyme cleaves sialic acid residues from viral proteins and surface proteins of infected cells, preventing clumping of newly released virions and sticking to cells that are already infected. By preventing these actions, neuraminidase inhibitors impede viral spread. Decreased susceptibility to the drugs is associated with mutations in viral neuraminidase. 

Treatment of erythrocytes with neuraminidase (Stewart et al 1955, 1957, Gardner et al 1961, Perona et al 1964) or intravenous injection of this enzyme (Landaw et al 1973) leads to a drastic decrease of their half-life in the circulation, in man it is reduced from about 120 days to a few hours (Halbhuber et al 1972, Durocher et al 1975, Jancik et al 1978). In vitro experiments revealed that the recognition mechanism of asialo-erythrocytes has very much in common with the uptake of soluble asialo-glycoproteins, though the blood cells are degraded exclusively in Kupffer cells (Halbhuber er al 1972), while asialo-glycoproteins are taken up by hepatocytes (Ashwell and Morell 1974). 

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