Zanamivir
From Proteopedia
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===Mechanism of Action=== | ===Mechanism of Action=== | ||
| - | Viral [[Neuraminidase]] is one of two major glycoproteins found on the surface of [[influenza]] viral membranes, the other being [[hemagglutinin]]. When the influenza virus infects a host cell, it attaches itself to the host via hemagglutinin interactions with host glycans, fascilitating the fusion of host endosomal membrane with the viral membrane. After the virus has successfully infected the host and replicated extensively, the viral cargo is released from the cell via budding. During the budding process, the viral cargo is attached to the host cell once again via hemagglutinins, allowing the viral particle to form completely. Once the viral particle is formed, Neuraminidase cleaves the terminal sialic (neuraminic) acid residues from the glycan structures on the surface of the infected cell, breaking the hemmaglutinin-glycan interaction and promoting release of the viral particle to infect other cells. Zanamivir functions by inhibiting the function of <scene name='Zanamivir/Neuro/1'>viral neuraminidase</scene>, preventing the viral particle from being released from the infected cell, thus limiting the severity and spread of [[viral infections]].<ref>PMID:1438172</ref> It binds to the active site of Neuraminidase | + | Viral [[Neuraminidase]] is one of two major glycoproteins found on the surface of [[influenza]] viral membranes, the other being [[hemagglutinin]]. When the influenza virus infects a host cell, it attaches itself to the host via hemagglutinin interactions with host glycans, fascilitating the fusion of host endosomal membrane with the viral membrane. After the virus has successfully infected the host and replicated extensively, the viral cargo is released from the cell via budding. During the budding process, the viral cargo is attached to the host cell once again via hemagglutinins, allowing the viral particle to form completely. Once the viral particle is formed, Neuraminidase cleaves the terminal sialic (neuraminic) acid residues from the glycan structures on the surface of the infected cell, breaking the hemmaglutinin-glycan interaction and promoting release of the viral particle to infect other cells. Zanamivir functions by inhibiting the function of <scene name='Zanamivir/Neuro/1'>viral neuraminidase</scene>, preventing the viral particle from being released from the infected cell, thus limiting the severity and spread of [[viral infections]].<ref>PMID:1438172</ref> It binds to the active site of Neuraminidase causing dramatic conformational adjustments which render the protein non-functional. This in effect prevents neuraminidase from cleaving the hemmaglutinin-glycan tethers and releasing the viral cargo after viral replication. Zanamivir binding causes the so-called 150 loop to shift, covering the binding pocket, while Zanamivir situates itself firmly within the active site using residues ___.<ref>doi: 10.1128/JVI.00959-08</ref> |
| - | + | H274Y | |
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
Revision as of 13:07, 12 December 2010
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Better Known as: Relenza
- Marketed By: GlaxoSmithKline
- Major Indication: Influenza Infection
- Drug Class: Neuraminidase Inhibitor
- Date of FDA Approval (Patent Expiration): 1999 (2016)
- 2009 Sales: $1.1 Billion
- Importance: It was the first neuraminidase inhibitor to be approved by the FDA, followed a few months later by Oseltamivir. Newer strains of flu virus, primarily H1N1, have developed varying levels of resistance to Oseltamivir, but a lesser extent to Zanamivir. Sales have increased dramatically since 2006 with scares of bird flu and swine flu pandemics.
- See Pharmaceutical Drugs for more information about other drugs and diseases.
Mechanism of Action
Viral Neuraminidase is one of two major glycoproteins found on the surface of influenza viral membranes, the other being hemagglutinin. When the influenza virus infects a host cell, it attaches itself to the host via hemagglutinin interactions with host glycans, fascilitating the fusion of host endosomal membrane with the viral membrane. After the virus has successfully infected the host and replicated extensively, the viral cargo is released from the cell via budding. During the budding process, the viral cargo is attached to the host cell once again via hemagglutinins, allowing the viral particle to form completely. Once the viral particle is formed, Neuraminidase cleaves the terminal sialic (neuraminic) acid residues from the glycan structures on the surface of the infected cell, breaking the hemmaglutinin-glycan interaction and promoting release of the viral particle to infect other cells. Zanamivir functions by inhibiting the function of , preventing the viral particle from being released from the infected cell, thus limiting the severity and spread of viral infections.[1] It binds to the active site of Neuraminidase causing dramatic conformational adjustments which render the protein non-functional. This in effect prevents neuraminidase from cleaving the hemmaglutinin-glycan tethers and releasing the viral cargo after viral replication. Zanamivir binding causes the so-called 150 loop to shift, covering the binding pocket, while Zanamivir situates itself firmly within the active site using residues ___.[2]
H274Y
Pharmacokinetics
For References to Pharmacokinetic data, see: References |
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References
- ↑ Varghese JN, McKimm-Breschkin JL, Caldwell JB, Kortt AA, Colman PM. The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins. 1992 Nov;14(3):327-32. PMID:1438172 doi:http://dx.doi.org/10.1002/prot.340140302
- ↑ Xu X, Zhu X, Dwek RA, Stevens J, Wilson IA. Structural characterization of the 1918 influenza virus H1N1 neuraminidase. J Virol. 2008 Nov;82(21):10493-501. Epub 2008 Aug 20. PMID:18715929 doi:10.1128/JVI.00959-08
