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. It was designed to be a Sialic acid analog. 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, facilitating 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 prevents neuraminidase from cleaving the hemmaglutinin-glycan tethers and releasing the viral cargo after viral replication. Zanamivir binding causes the (residues 147-151) to shift, , while Zanamivir situates itself using significant hydrogen bonding Arg 118, Asp 151, Arg 152, Arg 224, Glu 276, Arg 292, Arg 371 and Tyr 406. Of note, His 274, for which the H274Y mutation confers resistance to inhibitors like Oseltamivir, , explaining why the H274Y Neuraminidase mutant is not resistant to treatment with Zanamvir.[2]