Neuraminidase inhibitor

Neuraminidase inhibitors (NAIs) are a class of drugs which block the neuraminidase enzyme. They are a commonly used antiviral drug type against influenza. Viral neuraminidases are essential for influenza reproduction, facilitating viral budding from the host cell. Oseltamivir (Tamiflu), zanamivir (Relenza), laninamivir (Inavir), and peramivir belong to this class. Unlike the M2 inhibitors, which work only against the influenza A virus, NAIs act against both influenza A and influenza B.[1][2][3][4]

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.[5] 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.[6]

The efficacy was highly debated in recent years.[7][8][9] However, after the pandemic caused by H1N1 in 2009, the effectiveness of early treatment with neuraminidase inhibitors in reducing serious cases and deaths was reported in various countries.[10][11][12][13]

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.[14] 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.[14] 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.[15]

Common side effects include nausea and vomiting. The abnormal behaviors of children after taking oseltamivir that have been reported may be an extension of delirium or hallucinations caused by influenza.[14] 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.[14]

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  3. ^ This flash animation shows the mode of action of oseltamivir (Tamiflu) Archived 2005-10-23 at the Wayback Machine. pharmasquare.org
  4. ^ Replication of influenza virus Archived 2021-01-28 at the Wayback Machine. mvm.ed.ac.uk
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  6. ^ Ishizuka H, Yoshiba S, Okabe H, Yoshihara K (November 2010). "Clinical pharmacokinetics of laninamivir, a novel long-acting neuraminidase inhibitor, after single and multiple inhaled doses of its prodrug, CS-8958, in healthy male volunteers". Journal of Clinical Pharmacology. 50 (11): 1319–1329. doi:10.1177/0091270009356297. PMID 20145259. S2CID 20157230.
  7. ^ Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ (April 2014). "Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments". BMJ. 348: g2545. doi:10.1136/bmj.g2545. PMC 3981975. PMID 24811411.
  8. ^ Hsu J, Santesso N, Mustafa R, Brozek J, Chen YL, Hopkins JP, et al. (April 2012). "Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies". Annals of Internal Medicine. 156 (7): 512–524. doi:10.7326/0003-4819-156-7-201204030-00411. PMC 6679687. PMID 22371849.
  9. ^ Heneghan CJ, Onakpoya I, Thompson M, Spencer EA, Jones M, Jefferson T (April 2014). "Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments". BMJ. 348: g2547. doi:10.1136/bmj.g2547. PMC 3981976. PMID 24811412.
  10. ^ Louie JK, Acosta M, Jamieson DJ, Honein MA (January 2010). "Severe 2009 H1N1 influenza in pregnant and postpartum women in California". The New England Journal of Medicine. 362 (1): 27–35. doi:10.1056/nejmoa0910444. PMID 20032319.
  11. ^ Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, et al. (November 2009). "Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009". The New England Journal of Medicine. 361 (20): 1935–1944. CiteSeerX 10.1.1.183.7888. doi:10.1056/NEJMoa0906695. PMID 19815859.
  12. ^ Domínguez-Cherit G, Lapinsky SE, Macias AE, Pinto R, Espinosa-Perez L, de la Torre A, et al. (November 2009). "Critically Ill patients with 2009 influenza A(H1N1) in Mexico". JAMA. 302 (17): 1880–1887. doi:10.1001/jama.2009.1536. PMID 19822626.
  13. ^ Zarychanski R, Stuart TL, Kumar A, Doucette S, Elliott L, Kettner J, Plummer F (February 2010). "Correlates of severe disease in patients with 2009 pandemic influenza (H1N1) virus infection". CMAJ. 182 (3): 257–264. doi:10.1503/cmaj.091884. PMC 2826467. PMID 20093297.
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  15. ^ "CDC Online Newsroom - "Have You Heard?" Archive: 2014 - Influenza A Variant Virus". cdc.gov.