Viral neuraminidase - Virus Replication

Viral neuraminidase is an enzyme on the surface of influenza viruses that enables the virus to be released from the host cell. Drugs that inhibit neuraminidase are used to treat influenza.

When influenza virus reproduces, it moves to the cell surface with a hemagglutinin molecule on the surface of the virus bound to a sialic acid receptor on the surface of the cell. In order for the virus to be released free from the cell, neuraminidase must break apart (cleave) the sialic acid receptor. ^[2]

The enzyme helps viruses to be released from a host cell. Influenza virus membranes contain two glycoproteins: haemagglutinin and neuraminidase. While the hemagglutinin on the surface of the virion is needed for infection, its presence inhibits release of the particle after budding. It also mediates cell-surface sialic acid receptor binding to initiate virus infection. Viral neuraminidase cleaves terminal neuraminic acid (also called sialic acid) residues from glycan structures on the surface of the infected cell. This promotes the release of progeny viruses and the spread of the virus from the host cell to uninfected surrounding cells. Neuraminidase also cleaves sialic acid residues from viral proteins, preventing aggregation of viruses.

Neuraminidase has been targeted in structure-based enzyme inhibitor design programmes that have resulted in the production of two drugs, zanamivir (Relenza) and oseltamivir (Tamiflu)^[3]. Administration of neuraminidase inhibitors is a treatment that limits the severity and spread of viral infections. Neuraminidase inhibitors are useful for combating influenza infection: zanamivir, administered by inhalation; oseltamivir, administered orally; and under research is peramivir administered parenterally, that is through intravenous or intramuscular injection.