Viral neuraminidase - AbsoluteAstronomy.com

Viral neuraminidase is a type of neuraminidase

Neuraminidase

Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...

found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s that cleave sialic acid

Sialic acid

Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...

groups from glycoprotein

Glycoprotein

Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

s and are required for influenza virus replication.

When influenza virus replicates, it attaches to the cell surface using hemagglutinin, a molecule found on the surface of the virus that binds to sialic acid groups. Sialic acids are found on various glycoprotein

Glycoprotein

s at the host cell surface, and the virus exploits these groups to bind the host cell. In order for the virus to be released from the cell, neuraminidase must enzymatically cleave the sialic acid groups from host glycoprotein

Glycoprotein

s.
As an integral part of influenza replication, blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenza.

In some viruses including Mumps virus

Mumps virus

Mumps virus is the causative agent of mumps, a well-known common childhood disease characterised by swelling of the parotid glands and other epithelial tissues, causing high morbidity and in some cases more serious complications such as deafness...

and Human parainfluenza virus, a hemagglutinin-neuraminidase

Hemagglutinin-neuraminidase

Hemagglutinin-neuraminidase refers to a single viral protein that has both hemagglutinin and neuraminidase activity. This is in contrast to the proteins found in influenza, where both functions exist but in two separate proteins....

protein combines the neuraminidase and hemagglutinin

Hemagglutinin

Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...

functions in a single protein.

Function

The enzyme helps viruses to be released from a host cell. Influenza virus membranes contain two glycoprotein

Glycoprotein

s: hemagglutinin and neuraminidase. While the hemagglutinin

Hemagglutinin

on the surface of the virion is needed for infection, its presence inhibits release of the particle after budding. Viral neuraminidase cleaves terminal neuraminic acid

Neuraminic acid

Neuraminic acid is a 9-carbon monosaccharide, a derivative of a ketononose. Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine...

(also called sialic acid

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 inhibitors

Neuraminidase has been targeted in structure-based enzyme inhibitor design programmes that have resulted in the production of two drugs, zanamivir (Relenza) and oseltamivir

Oseltamivir

Oseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...

(Tamiflu). Administration of neuraminidase inhibitor

Neuraminidase inhibitor

Neuraminidase inhibitors are a class of antiviral drugs targeted at the influenza virus, which work by blocking the function of the viral neuraminidase protein, thus preventing the virus from reproducing by budding from the host cell....

s is a treatment that limits the severity and spread of viral infections. Neuraminidase inhibitors are useful for combating influenza

Influenza

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...

infection: zanamivir, administered by inhalation; oseltamivir

Oseltamivir

, administered orally; and under research is peramivir

Peramivir

Peramivir is an experimental antiviral drug developed by BioCryst Pharmaceuticals for the treatment of influenza. It has been authorized for the emergency use of treatment of certain hospitalized patients with known or suspected 2009 H1N1 influenza....

administered parenterally, that is through intravenous or intramuscular injection.

Neuraminidase inhibition resistance

On February 27, 2005, a 14-year-old Vietnamese girl was documented to be carrying an H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

influenza virus strain that was resistant to the drug oseltamivir

Oseltamivir

. The drug is used to treat patients that have contracted influenza. However, the Vietnamese girl who had received a prophylactic dose (75 mg once a day) was found to be non-responsive to the medication. In growing fears of a global avian flu pandemic, scientists began to look for a cause of resistance to the Tamiflu medication. The cause was determined to be a histidine-to-tyrosine (amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

) substitution at position 274 in its neuraminidase protein.

As strains of influenza are continuously mutating, it is essential that scientists quickly and efficiently determine the correct neuraminidase subtype that is responsible for the drug resistance in order to develop medications that will combat specific strains of influenza.

Specificity

In ideal circumstances, influenza virus neuraminidase (NA) should act on the same type of receptor the virus hemagglutinin

Hemagglutinin

(HA) binds to, a phenomenon that does not always happen. It is not quite clear how the virus manages to function when there is no close match between the specificities of NA and HA.

Exo- and endo-

Neuraminidase enzymes can have endo- or exo-glycosidase activity, and are classified as EC 3.2.1.29 (endo-neuraminidase) and EC 3.2.1.18 (exo-neuraminidases). In general, mammalian sialic acid residues are at terminal positions (non-reducing end) in complex glycans, and so viral neuraminidases - which are exo-glycosidase enzymes - use these terminal residues as their substrates.

External links

Influenza Research Database Database of influenza sequences (including neuraminidase).

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.

Function

Neuraminidase inhibitors

Neuraminidase inhibition resistance

Specificity

Exo- and endo-

See also

External links