Logo of embojLink to Publisher's site
EMBO J. 1985 Nov; 4(11): 3021–3024.
PMCID: PMC554613

The molecular basis of the specific anti-influenza action of amantadine.


Amantadine (1-aminoadamantane hydrochloride) is effective in the prophylaxis and treatment of influenza A infections. In tissue culture this selective, strain-specific antiviral activity occurs at relatively low concentrations (5 microM or less), which inhibit either the initiation of infection or virus assembly. The data reported here demonstrate that the basis of these actions is similar and resides in the virus-coded M2 membrane protein, the product of a spliced transcript of RNA segment 7. Mutations which confer resistance to amantadine are restricted to four amino acids within a hydrophobic sequence, indicating that the drug is targetted against the putative membrane-associated portion of the molecule. The influence of the virus haemagglutinin on the amantadine sensitivity of virus strains implies that the drug may interfere with interactions between these two virus proteins.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (747K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Appleyard G. Amantadine-resistance as a genetic marker for influenza viruses. J Gen Virol. 1977 Aug;36(2):249–255. [PubMed]
  • Appleyard G, Maber HB. A plaque assay for the study of influenza virus inhibitors. J Antimicrob Chemother. 1975 Dec;1(4 Suppl):49–53. [PubMed]
  • Daniels RS, Downie JC, Hay AJ, Knossow M, Skehel JJ, Wang ML, Wiley DC. Fusion mutants of the influenza virus hemagglutinin glycoprotein. Cell. 1985 Feb;40(2):431–439. [PubMed]
  • Dolin R, Reichman RC, Madore HP, Maynard R, Linton PN, Webber-Jones J. A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. N Engl J Med. 1982 Sep 2;307(10):580–584. [PubMed]
  • Hay AJ. Studies on the formation of the influenza virus envelope. Virology. 1974 Aug;60(2):398–418. [PubMed]
  • Hay AJ, Kennedy NC, Skehel JJ, Appleyard G. The matrix protein gene determines amantadine-sensitivity of influenza viruses. J Gen Virol. 1979 Jan;42(1):189–191. [PubMed]
  • Helenius A, Kartenbeck J, Simons K, Fries E. On the entry of Semliki forest virus into BHK-21 cells. J Cell Biol. 1980 Feb;84(2):404–420. [PMC free article] [PubMed]
  • Helenius A, Marsh M, White J. Inhibition of Semliki forest virus penetration by lysosomotropic weak bases. J Gen Virol. 1982 Jan;58(Pt 1):47–61. [PubMed]
  • Lamb RA, Lai CJ, Choppin PW. Sequences of mRNAs derived from genome RNA segment 7 of influenza virus: colinear and interrupted mRNAs code for overlapping proteins. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4170–4174. [PMC free article] [PubMed]
  • Lamb RA, Zebedee SL, Richardson CD. Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface. Cell. 1985 Mar;40(3):627–633. [PubMed]
  • Lubeck MD, Schulman JL, Palese P. Susceptibility of influenza A viruses to amantadine is influenced by the gene coding for M protein. J Virol. 1978 Dec;28(3):710–716. [PMC free article] [PubMed]
  • McCauley JW, Mahy BW, Inglis SC. Nucleotide sequence of fowl plague virus RNA segment 7. J Gen Virol. 1982 Jan;58(Pt 1):211–215. [PubMed]
  • Ortín J, Martínez C, del Río L, Dávila M, López-Galíndez C, Villanueva N, Domingo E. Evolution of the nucleotide sequence of influenza virus RNA segment 7 during drift of the H3N2 subtype. Gene. 1983 Aug;23(2):233–239. [PubMed]
  • Oxford JS, Galbraith A. Antiviral activity of amantadine: a review of laboratory and clinical data. Pharmacol Ther. 1980;11(1):181–262. [PubMed]
  • Patel TP, Millican TA, Bose CC, Titmas RC, Mock GA, Eaton MA. Improvements to solid phase phosphotriester synthesis of deoxyoligonucleotides. Nucleic Acids Res. 1982 Sep 25;10(18):5605–5620. [PMC free article] [PubMed]
  • Porter AG, Barber C, Carey NH, Hallewell RA, Threlfall G, Emtage JS. Complete nucleotide sequence of an influenza virus haemagglutinin gene from cloned DNA. Nature. 1979 Nov 29;282(5738):471–477. [PubMed]
  • PORTERFIELD JS. A simple plaque-inhibition test for the study of arthropod-borne viruses. Bull World Health Organ. 1960;22:373–380. [PMC free article] [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Schiffer M, Edmundson AB. Use of helical wheels to represent the structures of proteins and to identify segments with helical potential. Biophys J. 1967 Mar;7(2):121–135. [PMC free article] [PubMed]
  • Skehel JJ, Hay AJ, Armstrong JA. On the mechanism of inhibition of influenza virus replication by amantadine hydrochloride. J Gen Virol. 1978 Jan;38(1):97–110. [PubMed]
  • Scholtissek C, Faulkner GP. Amantadine-resistant and -sensitive influenza A strains and recombinants. J Gen Virol. 1979 Sep;44(3):807–815. [PubMed]
  • Wallbank AM, Matter RE, Klinikowski NG. 1-Adamantanamine hydrochloride: inhibition of Rous and Esh Sarcoma viruses in cell culture. Science. 1966 Jun 24;152(3730):1760–1761. [PubMed]
  • Winter G, Fields S. Cloning of influenza cDNA ino M13: the sequence of the RNA segment encoding the A/PR/8/34 matrix protein. Nucleic Acids Res. 1980 May 10;8(9):1965–1974. [PMC free article] [PubMed]
  • Yoshimura A, Kuroda K, Kawasaki K, Yamashina S, Maeda T, Ohnishi S. Infectious cell entry mechanism of influenza virus. J Virol. 1982 Jul;43(1):284–293. [PMC free article] [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...