Neuraminidase inhibitors zanamivir

Neuraminidase is an essential viral glycoprotein for virus replication and release. The neuraminidase inhibitors zanamivir and oseltamivir have recently been approved for the treatment of acute uncomplicated influenza infection. When a 5-day course of therapy is initiated within 36-48 hours after the onset of symptoms, use of either agent shortens the severity and duration of illness and may decrease the incidence of respiratory complications in children and adults. Unlike amantadine and rimantidine, zanamivir and oseltamivir have activity against both influenza A and influenza B. Zanamivir is administered via oral inhaler. The compound displays poor oral bioavailability, limited plasma protein binding, rapid renal clearance, and absence of significant metabolism. Nasal and throat discomfort may occur—as well as bronchospasm in patients with reactive airway disease. 

Figure 6.17. Crystal structure (PDB entry la4q) of the neuraminidase inhibitor zanamivir bound in tltie active site (213).

McNichoIi IR, McNichoII JJ. Neuraminidase inhibitors zanamivir and oseltamivir. Ann Pharmacother 2001 35(l) 57-70. 

Hayden FG, Osterhaus AD, Treanor JJ, Fleming DM, Aoki FY, Nicholson KG, Bohnen AM, Hirst HM, Keene O, Wightman K. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus... 

Influenza Neuraminidase Inhibitors Zanamivir and Oseltamivir as Drugs for the Treatment of Influenza... 

Due to the transfer mechanism of TcTS analogous to those of sialidases [25] the prototype of sialidase inhibitors Neu5Ac2en 99 [57] was tested. Compound 99 as well as the potent influenza virus neuraminidase inhibitors zanamivir (Relenza, 100) and the active form of oseltamivir (Tamiflu, 101) with analogous structures of transition state were also of interest as potential inhibitors of TcTS. However, as determined for 99 the TcTS activity was inhibited with only Ki = 12.29 mM (Fig. 15) [33]. 

Magano J. Synthetic approaches to the neuraminidase inhibitors zanamivir (Relenza) and oseltamivir phosphate (Tami-flu) for the treatment of influenza. Chem. Rev. 2009 109 4398 38. 

The influenza virus inhibitors, zanamivir, and oseltamivir, act outside the cell after virus particles have been formed. The dtugs have been designed to fit into the active site of the viral envelope enzyme neuraminidase, which is required to cleave sialic acid off the surface of the producing cells. When its activity is blocked, new virus particles stay attached to the cell surface through binding of the virus protein hemagglutinin to sialic acid and are prevented from spreading to other cells. 

Neuraminidase inhibitors are the major class of drugs to treat or to prevent the infection with influenza viruses. Currently, two neuraminidase inhibitors are available, zanamivir and oseltamivir, which block the release of new influenza vims from infected host cells and thereby stop the spread of infection. The enzyme neuraminidase is a surface glycoprotein present on all influenza viruses. There are nine influenza neuraminidase sub-types known of which subtypes N1 and N2 appear to be the most important ones. Neuraminidase inhibitors are effective against all neuraminidase subtypes. The activity of the neuraminidase is required for the newly... 

Two neuraminidase inhibitors (oseltamivir carboxylate and zanamivir) are approved for prevention and treatment of infections with both influenza A and B viruses as discussed in chapter by Itzstein and Thomson, this volume. Oseltamivir carboxylate (OC) has gained most use because it can be taken orally, whereas the current formulation of zanamivir has to be inhaled. In addition, the WHO reconunends oseltamivir for treatment of clinically confirmed cases of H5N1 and for post-exposme prophylaxis to control recent H5N1 avian influenza outbreaks. 

The two classes of antiviral drugs available for treatment of influenza are the same as those available for prophylaxis and include the adamantanes, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir. Because of widespread resistance to the adamantanes among influenza A viruses in the United States, amantadine and rimantadine are not recommended for treatment of influenza until susceptibility can be reestablished. 

Oseltamivir and zanamivir are neuraminidase inhibitors that have activity against both influenza A and influenza B viruses. When administered within 48 hours of the onset of illness, oseltamivir and zanamivir may reduce the duration of illness by approximately 1 day versus placebo. 

NEURAMINIDASE INHIBITORS FOR INFLUENZA OSELTAMIVIR PHOSPHATE (TAMIFLU ) AND ZANAMIVIR (RELENZA )... 

Zanamivir was the first orally active neuraminidase inhibitor commercially developed. It acts as a... 

Currently, two classes of drugs are available with antiviral activity against influenza viruses inhibitors of the ion channel activity of the M2 membrane protein, amantadine and rimantadine, and the neuraminidase inhibitors oseltamivir, and zanamivir. H5N1 viruses isolated from poultry and humans in Thailand and Viet Nam in 2004 invariably showed an amantadine-resistance indicating that amantadine treatment is not an option during the ongoing outb-treak in South-East Asia. 

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. 

Colman PM. Zanamivir an influenza virus neuraminidase inhibitor. Expert Rev Anti Infect Ther. 2005 3 191-199. 

Neuraminidase inhibitors prevent the release of influenza A and B viruses. Normally, the viral neuraminidase splits off N-acetyl-neuraminic (sialic) acid residues on the cellular surface coat, thereby enabling newly formed viral particles to be detached from the host cell. Zanamivir is given by inhalation oseltamivir is suitable for oral administration because it is an ester prodrug. Possible uses include treatment and prophylaxis of influenza virus infections. 

Oseltamivir and zanamivir are neuraminidase inhibitors that have activity against both influenza A and influenza B viruses. When administered within 48 hours of the onset of illness, oseltamivir and zanamivir may reduce the duration of illness by approximately 1 day versus placebo. Oseltamivir is approved for treatment in those older than the age of 1 year, while zanamivir is approved for treatment in those older than the age of 7 years. The recommended dosages vary by agent and age (see Table 41-3), and the recommended duration of treatment for both agents is 5 days. The FDA has received 103 reports, occurring between August 29,2005, and July 6,2006, of delirium, hallucinations, and self-injury in pediatric patients (mostly from Japan) following treatment with oseltamivir. 

Zanamivir is a neuraminidase inhibitor which blocks entry of the influenza A and B viruses to target cells and the release of their progeny. It is administered as 5 mg of a dry powder twice daily in 5-day course via a special inhaler. Controlled trials have shown that the duration of symptoms is reduced from about 6 to 5 days, with a smaller reduction in the mean time taken to return to normal activities. In high-risk groups the reduction in duration of symptoms is a little greater, and fewer patients need antibiotics. 

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