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Bio-Algorithms and Med-Systems

Editor-in-Chief: Roterman-Konieczna , Irena

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Drug generations that combat influenza A virus infection

Gabriela Żaroffe
  • Corresponding author
  • Department of Molecular Biology, Faculty of Biological Sciences, University of Zielona Góra, Zielona Góra, Poland
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/ Jacek Leluk
  • Department of Molecular Biology, Faculty of Biological Sciences, University of Zielona Góra, Zielona Góra, Poland
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/ Agata Żyźniewska
  • Department of Molecular Biology, Faculty of Biological Sciences, University of Zielona Góra, Zielona Góra, Poland
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/ Rafał Filip
  • Department of Molecular Biology, Faculty of Biological Sciences, University of Zielona Góra, Zielona Góra, Poland
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Published Online: 2017-02-11 | DOI: https://doi.org/10.1515/bams-2016-0027


Influenza viruses are significant human respiratory pathogens that cause infections and unpredictable pandemic outbreaks. M2 ion-channel protein, participating in the transmission of viral genetic materials into infected cells, is considered to be the crucial target for old-generation drugs such as rimantadine and amantadine. Neuraminidase protein, which is responsible for the replication of the influenza virus, is affected by the new generation of drugs, including oseltamivir (Tamiflu) and zanamivir (Relenza). The virus mutations that cause oseltamivir resistance are also described. This review presents the details concerning the treatment of influenza neuraminidase inhibitors against the H5N1 strain. It also describes virus mutations that cause resistance to oseltamivir and presents a new drug, peramivir, which is a neuraminidase inhibitor that was introduced against the H1N1 epidemic. This work specifies the details of the pharmacokinetics, dosing, toxicity, side effects, and efficiency of the drugs being used against influenza A virus infections.

Keywords: amantadine; M2 ion-channel protein; neuraminidase; oseltamivir; peramivir; rimantadine; zanamivir


  • 1.

    Monto AS, Mckimm-Breschkin JL, Macken C, Hampson AW, Hay A, Klimov A, et al. Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3 years of their use. Antimicrob Agents Chemother 2006;50:2395–402.Google Scholar

  • 2.

    Machała MK, Brydak LB. Grypa w różnych aspektach. Część I-Budowa, replikacja i zmienność wirusów grypy oraz przebieg kliniczny choroby, odpowiedź immunologiczna i diagnostyka laboratoryjna. Akademia Medyczna Warszawa. Pol Merk Lek 2006;XII:123–270.Google Scholar

  • 3.

    Nitsch-Osuch A, Brydak LB, Wardyn AK. Inhibitory neuraminidazy w profilaktyce i leczeniu grypy; Praca poglądowa Warszawski Uniwersytet Medyczny, Katedra i Zakład Medycyny Rodzinnej z Oddziałem Klinicznym Chorób Wewnętrznych i Metabolicznych, kierownik: prof. dr hab. med. A.K. Wardyn; Narodowy Instytut Zdrowia Publicznego – Państwowy Zakład Higieny, Krajowy Ośrodek ds. Grypy, kierownik: prof. dr hab. L.B. BrydakGoogle Scholar

  • 4.

    Bright RA, Medina MJ, Xu X, Perez-Oronoz G, Wallis TR, Davis XM, et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 2005;366:1175–81.Google Scholar

  • 5.

    Cass LM, Efthymiopoulos C, Bye A. Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers. Clin Pharmacokinet 1999;36(Suppl 1):1–11.Google Scholar

  • 6.

    Capparelli EV, Stevens RC, Chow MS, Izard M, Wills RJ. Rimantadine pharmacokinetics in healthy subjects and patients with end-stage renal failure. Clin Pharmacol Ther 1988;43:536–41.Google Scholar

  • 7.

    Aoki FY, Doucette KE. Oseltamivir: a clinical and pharmacological perspective. Expert Opin Pharmacother 2001;2:1671–83.Google Scholar

  • 8.

    Herlocher ML, Truscon R, Elias S, Yen HL, Roberts NA, Ohmit SE, et al. Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis 2004;190:1627–30.Google Scholar

  • 9.

    He G, Massarella J, Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet 1999;37:471–84.Google Scholar

  • 10.

    Hayden FG, Minocha A, Spyker DA, Hoffman HE. Comparative single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride in young and elderly adults. Antimicrob Agents Chemother 1985;28:216–21.Google Scholar

  • 11.

    Webster A, Boyce M, Edmundson S, Miller I. Coadministration of orally inhaled zanamivir with inactivated trivalent influenza vaccine does not adversely affect the production of antihaemagglutinin antibodies in the serum of healthy volunteers. Clin Pharmacokinet 1999;36(Suppl 1):51.Google Scholar

  • 12.

    Hayden FG, Monto AS. Oral rimantadine hydrochloride therapy of influenza A virus H3N2 subtype infection in adults. Antimicrob Agents Chemother 1986;29:339–41.Google Scholar

  • 13.

    Human health issues related to avian influenza in Canada. http://www.phacaspc.gc.ca. October 25, 2006.

  • 14.

    Monto AS, Robinson DP, Herlocher ML, Hinson Jr JM, Elliott MJ, Crisp A. Zanamivir in the prevention of influenza among healthy adults. A randomized controlled trial. J Am Med Assoc 1999;282:31–5.Google Scholar

  • 15.

    Ilyushima N. Combination therapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res 2006;70:121–31.Google Scholar

  • 16.

    Jefferson T, Demicheli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A. Antivirals for influenza in healthy adults: systematic review. Lancet 2006;367:303–13.Google Scholar

  • 17.

    Li KS, Guan Y, Wang J, Smith GJ, Xu KM, Duan L, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 2004;430:209–13.Google Scholar

  • 18.

    Leneva IA, Roberts N, Govorkova EA, Goloubeva OG, Webster RG. The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Res 2000;48:101–15.Google Scholar

  • 19.

    Le L, Leluk J. Study on phylogenetic relationships, variability, and correlated mutations in M2 proteins of influenza virus A. PLoS One 2011;6:e22970.Google Scholar

  • 20.

    Wills Rj, Belshe R, Tomlinsin D, De Grazia F, Lin A, Wells S, et al. Pharmacokinetics of rimantadine hydrochloride in patients with chronic liver disease. Clin Pharmacol Ther 1987;42:449–54.Google Scholar

  • 21.

    Lin JT, Yu XZ, Cui DJ, Chen XY, Zhu JH, Wang YZ, et al. A multicentre, randomized, controlled trial of oseltamivir in the treatment of influenza in a high-risk Chinese population. Curr Med Res Opin 2006;22:75–82.Google Scholar

  • 22.

    Lew W, Chen X, Kim CU. Discovery and development of GS 4104 (oseltamivir): an orally active influenza neuraminidase inhibitor. Curr Med Chem 2000;7:663–72.Google Scholar

  • 23.

    Lim JK, Wooten D, Siegel R, Cheung RC. Amantadine in treatment of chronic hepatitis C virus infection. J Viral Hepat 2005;12:445–55.Google Scholar

  • 24.

    McNicholl IR, McNicholl JJ. Neuraminidase inhibitors: zanamivir and oseltamivir. Ann Pharmacother 2001;35:57–70.Google Scholar

  • 25.

    Monto AS, Ohmit, SE, Hornbuckle K, Pearce CL. Safety and efficacy of long-term use of rimantadine for prophylaxis of type A influenza in nursing homes. Antimicrob Agents Chemother 1995;39:2224–8.Google Scholar

  • 26.

    Oo C, Hill G, Dorr A, Liu B, Boellner S, Ward P. Pharmacokinetics of anti-influenza prodrug oseltamivir in children aged 1–5 years. Eur J Clin Pharmacol 2003;59:411–5.Google Scholar

About the article

Received: 2016-12-10

Accepted: 2017-01-11

Published Online: 2017-02-11

Published in Print: 2017-03-01

Author contributions: The authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Bio-Algorithms and Med-Systems, Volume 13, Issue 1, Pages 1–11, ISSN (Online) 1896-530X, ISSN (Print) 1895-9091, DOI: https://doi.org/10.1515/bams-2016-0027.

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