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. 1973 Oct;4(4):421–426. doi: 10.1128/aac.4.4.421

In Vitro Antiviral Activity and Preliminary Clinical Trials of a New Adamantane Compound

Asha Mathur a,1, A S Beare a, Sylvia E Reed a
PMCID: PMC444570  PMID: 4364762

Abstract

A compound, 1′-methyl spiro (adamantane-2,3′-pyrrolidine) maleate, chemically related to the antiviral drug amantadine, was tested for activity in vitro against a number of human respiratory viruses. By a variety of techniques, it was shown to be active against a wide range of human and animal influenza A viruses. The effect was, however, variable and ranged from high activity against two 1957 Asian strains to no observable activity against a 1971 strain. Like amantadine, the drug did not inhibit the growth of influenza B viruses. It was also inactive against a number of paramyxoviruses. Unlike amantadine, the drug did inhibit rhinoviruses, but to a lesser extent than myxoviruses. The coronavirus 229E was also sensitive to the action of the drug in vitro. Although an earlier trial in volunteers showed that, when given orally from 2 days before until 5 days after virus challenge, the drug was protective against infection with influenza A/Hong Kong/68 virus, a similar trial in volunteers challenged with rhinoviruses 2 and 9 revealed no useful activity against rhinoviruses in man.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beare A. S., Hall T. S. Recombinant influenza-A viruses as live vaccines for man. Report to the Medical Research Council's Committee on Influenza and other Respiratory Virus Vaccines. Lancet. 1971 Dec 11;2(7737):1271–1273. doi: 10.1016/s0140-6736(71)90597-6. [DOI] [PubMed] [Google Scholar]
  2. Beare A. S., Hall T. S., Tyrrell D. A. Protection of volunteers against challenge with A-Hong Kong-68 influenza virus by a new adamantane compound. Lancet. 1972 May 13;1(7759):1039–1040. doi: 10.1016/s0140-6736(72)91220-2. [DOI] [PubMed] [Google Scholar]
  3. Beare A. S., Keast K. Plaque formation by influenza B viruses in primary calf kidney cell monolayes. J Gen Virol. 1971 Nov;13(2):321–325. doi: 10.1099/0022-1317-13-2-321. [DOI] [PubMed] [Google Scholar]
  4. Bradburne A. F. Sensitivity of L132 cells to some "new" respiratory viruses. Nature. 1969 Jan 4;221(5175):85–86. doi: 10.1038/221085a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradburne A. F., Tyrrell D. A. The propagation of "coronaviruses" in tissue-culture. Arch Gesamte Virusforsch. 1969;28(2):133–150. doi: 10.1007/BF01249379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DAVIES W. L., GRUNERT R. R., HAFF R. F., MCGAHEN J. W., NEUMAYER E. M., PAULSHOCK M., WATTS J. C., WOOD T. R., HERMANN E. C., HOFFMANN C. E. ANTIVIRAL ACTIVITY OF 1-ADAMANTANAMINE (AMANTADINE). Science. 1964 May 15;144(3620):862–863. doi: 10.1126/science.144.3620.862. [DOI] [PubMed] [Google Scholar]
  7. Fiala M., Kenny G. E. Enhancement of rhinovirus plaque formation in human heteroploid cell cultures by magnesium and calcium. J Bacteriol. 1966 Dec;92(6):1710–1715. doi: 10.1128/jb.92.6.1710-1715.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hoffmann C. E., Neumayer E. M., Haff R. F., Goldsby R. A. Mode of Action of the Antiviral Activity of Amantadine in Tissue Culture. J Bacteriol. 1965 Sep;90(3):623–628. doi: 10.1128/jb.90.3.623-628.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hoorn B., Tyrrell D. A. Organ cultures in virology. Prog Med Virol. 1969;11:408–450. [PubMed] [Google Scholar]
  10. Jacobs J. P., Jones C. M., Baille J. P. Characteristics of a human diploid cell designated MRC-5. Nature. 1970 Jul 11;227(5254):168–170. doi: 10.1038/227168a0. [DOI] [PubMed] [Google Scholar]
  11. Kato N., Eggers H. J. Inhibition of uncoating of fowl plague virus by l-adamantanamine hydrochloride. Virology. 1969 Apr;37(4):632–641. doi: 10.1016/0042-6822(69)90281-5. [DOI] [PubMed] [Google Scholar]
  12. Kilbourne E. D. Future influenza vaccines and the use of genetic recombinants. Bull World Health Organ. 1969;41(3):643–645. [PMC free article] [PubMed] [Google Scholar]
  13. Long W. F., Olusanya J. Adamantanamine and early events following influenza virus infection. Arch Gesamte Virusforsch. 1972;36(1):18–22. doi: 10.1007/BF01250291. [DOI] [PubMed] [Google Scholar]
  14. Lundahl K., Schut J., Schlatmann J. L., Paerels G. B., Peters A. Synthesis and antiviral activities of adamantane spiro compounds. 1. Adamantane and analogous spiro-3'-pyrrolidines. J Med Chem. 1972 Feb;15(2):129–132. doi: 10.1021/jm00272a003. [DOI] [PubMed] [Google Scholar]
  15. McCahon D., Schild G. C. Segregation of antigenic and biological characteristics during influenza virus recombination. J Gen Virol. 1972 Apr;15(1):73–77. doi: 10.1099/0022-1317-15-1-73. [DOI] [PubMed] [Google Scholar]
  16. Okuno Y., Nakamura K. Prophylactic effectiveness of live influenza vaccine in 1965. Biken J. 1966 Jun;9(2):89–95. [PubMed] [Google Scholar]
  17. Schild G. C., Sutton R. N. Inhibition of influenza viruses in vitro and in vivo by 1-adamantanamine hydrochloride. Br J Exp Pathol. 1965 Jun;46(3):263–273. [PMC free article] [PubMed] [Google Scholar]
  18. Smorodintsev A. A., Karpuhin G. I., Zlydnikov D. M., Malyseva A. M., Svecova E. G., Burov S. A., Hramcova L. M., Romanov J. A., Taros L. J., Ivannikov J. G. The prophylactic effectiveness of amantadine hydrochloride in an epidemic of Hong Kong influenza in Leningrad in 1969. Bull World Health Organ. 1970;42(6):865–872. [PMC free article] [PubMed] [Google Scholar]
  19. Soto A. J., Hall T. S., Reed S. E. Trial of the antiviral action of isoprinosine against rhinovirus infection of volunteers. Antimicrob Agents Chemother. 1973 Mar;3(3):332–334. doi: 10.1128/aac.3.3.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stott E. J., Tyrrell D. A. Some improved techniques for the study of rhinoviruses using HeLa cells. Arch Gesamte Virusforsch. 1968;23(3):236–244. doi: 10.1007/BF01241896. [DOI] [PubMed] [Google Scholar]
  21. Togo Y., Hornick R. B., Felitti V. J., Kaufman M. L., Dawkins A. T., Jr, Kilpe V. E., Claghorn J. L. Evaluation of therapeutic efficacy of amantadine in patients with naturally occurring A2 influenza. JAMA. 1970 Feb 16;211(7):1149–1156. [PubMed] [Google Scholar]
  22. Tyrrell D. A., Bynoe M. L., Hoorn B. Studies on the antiviral activity of 1-adamantanamine. Br J Exp Pathol. 1965 Aug;46(4):370–375. [PMC free article] [PubMed] [Google Scholar]
  23. VOGEL J., SHELOKOV A. Adsorption-hemagglutination test for influenza virus in monkey kidney tissue culture. Science. 1957 Aug 23;126(3269):358–359. doi: 10.1126/science.126.3269.358-a. [DOI] [PubMed] [Google Scholar]
  24. Wingfield W. L., Pollack D., Grunert R. R. Therapeutic efficacy of amantadine HCl and rimantadine HCl in naturally occurring influenza A2 respiratory illness in man. N Engl J Med. 1969 Sep 11;281(11):579–584. doi: 10.1056/NEJM196909112811102. [DOI] [PubMed] [Google Scholar]

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