Neuraminidase inhibitors (NAIs) are a class of
drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
s which block the
neuraminidase
Exo-α-sialidase (EC 3.2.1.18, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:
: Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glycos ...
enzyme. They are a commonly used
antiviral drug
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do n ...
type against influenza.
Viral neuraminidase
Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid (also called neuraminic acid) groups from ...
s are essential for influenza reproduction, facilitating viral
budding
Budding or blastogenesis is a type of asexual reproduction in which a new organism develops from an outgrowth or bud due to cell division at one particular site. For example, the small bulb-like projection coming out from the yeast cell is know ...
from the host cell.
Oseltamivir
Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at hig ...
(Tamiflu),
zanamivir
Zanamivir is a medication used to treat and prevent influenza caused by influenza A and influenza B viruses. It is a neuraminidase inhibitor and was developed by the Australian biotech firm Biota Holdings. It was licensed to Glaxo in 1990 and ap ...
(Relenza),
laninamivir
Laninamivir (CS-8958) is a neuraminidase inhibitor that is a drug used for the treatment and prophylaxis of Influenzavirus A
'' A virus'' (''IAV'') causes influenza in birds and some mammals, and is the only species of the genus ''Alphainfluen ...
(Inavir), and
peramivir
Peramivir (trade name Rapivab) is an antiviral drug developed by BioCryst Pharmaceuticals for the treatment of influenza. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and th ...
belong to this class. Unlike the
M2 inhibitors, which work only against the influenza A virus, NAIs act against both
influenza A
'' A virus'' (''IAV'') causes influenza in birds and some mammals, and is the only species of the genus ''Alphainfluenzavirus'' of the virus family '' Orthomyxoviridae''. Strains of all subtypes of influenza A virus have been isolated from wi ...
and
influenza B
''Influenza B virus'' is the Monotypic taxon, only species in the genus ''Betainfluenzavirus'' in the virus family ''Orthomyxoviridae''.
Influenza B virus is known only to infect humans and Pinniped, seals. This limited host range is apparently ...
.
The NAIs oseltamivir and zanamivir were approved in the US and Europe for treatment and prevention of influenza A and B. Peramivir acts by strongly binding to the neuraminidase of the influenza viruses and inhibits activation of neuraminidase much longer than oseltamivir or zanamivir. However, laninamivir in the cells is slowly released into the respiratory tract, resulting in long-lasting anti-influenza virus activity. Thus the mechanism of the long-lasting activity of laninamivir is basically different from that of peramivir.
The efficacy was highly debated in recent years. However, after the pandemic caused by
H1N1
In virology, influenza A virus subtype H1N1 (A/H1N1) is a subtype of influenza A virus. Major outbreaks of H1N1 strains in humans include the Spanish flu, the 1977 Russian flu pandemic and the 2009 swine flu pandemic. It is an orthomyxovirus ...
in 2009, the effectiveness of early treatment with neuraminidase inhibitors in reducing serious cases and deaths was reported in various countries.
In countries where influenza-like illness is treated using NAIs on a national level, statistical reports show a low fatality record for symptomatic illness because of the universal implementation of early treatment using this class of drugs.
Although oseltamivir is widely used in these countries, there have been no outbreaks caused by oseltamivir-resistant viruses and also no serious illness caused by oseltamivir-resistant viruses has ever been reported.
The United States Centers for Disease Control and Prevention continues to recommend the use of oseltamavir treatment for people at high risk for complications and the elderly and those at lower risk who present within 48 hours of first symptoms of infection.
Common side effects include
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
and
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
. The abnormal behaviors of children after taking oseltamivir that have been reported may be an extension of
delirium
Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...
or hallucinations caused by influenza.
It occurs in the early stages of the illness, such as within 48 hours after onset of the illness. Therefore, children with influenza are advised to be observed by their parents until 48 hours after the onset of the influenza illness, regardless of whether the child is treated with NAIs.
Specific neuraminidase inhibitors
*
Laninamivir
Laninamivir (CS-8958) is a neuraminidase inhibitor that is a drug used for the treatment and prophylaxis of Influenzavirus A
'' A virus'' (''IAV'') causes influenza in birds and some mammals, and is the only species of the genus ''Alphainfluen ...
*
Oseltamivir
Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at hig ...
(Tamiflu)
*
Peramivir
Peramivir (trade name Rapivab) is an antiviral drug developed by BioCryst Pharmaceuticals for the treatment of influenza. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and th ...
(Rapivab)
*
Zanamivir
Zanamivir is a medication used to treat and prevent influenza caused by influenza A and influenza B viruses. It is a neuraminidase inhibitor and was developed by the Australian biotech firm Biota Holdings. It was licensed to Glaxo in 1990 and ap ...
(Relenza)
Structures of the viral neuraminidase inhibitors in use
Natural products
A natural product is a natural Chemical compound, compound or chemical substance, substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural product ...
* Cyanidin-3-sambubioside (extracted from
black elderberry
''Sambucus nigra'' is a species complex of flowering plants in the family Adoxaceae native to most of Europe. Common names include elder, elderberry, black elder, European elder, European elderberry, European black elderberry and tramman (Isle ...
)
*
Coptisine
Coptisine is an alkaloid found in Chinese goldthread (''Coptis chinensis''), greater celandine, and opium. Famous for the bitter taste that it produces, it is used in Chinese herbal medicine along with the related compound berberine
Berberine ...
*
Berberine
Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as ''Berberis vulgaris'' (barberry), '' Berberis aristata'' (tree turmeric), '' Mahonia aquifolium'' (Oregon grape), '' Hyd ...
See also
*
Discovery and development of neuraminidase inhibitors Neuraminidase inhibitors inhibit enzymatic activity of the enzyme neuraminidase (sialidase). These type of inhibitors have been introduced as anti-influenza drugs as they prevent the virus from exiting infected cells and thus stop further spreadin ...
References
External links
{{DEFAULTSORT:Neuraminidase Inhibitor
Carbohydrate chemistry