Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1983 Jun;23(6):808–813. doi: 10.1128/aac.23.6.808

Activity of 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)thymine against herpes simplex virus in cell cultures and rabbit eyes.

M D Trousdale, A B Nesburn, T L Su, C Lopez, K A Watanabe, J J Fox
PMCID: PMC184970  PMID: 6311085

Abstract

A new antiviral compound 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-uracil [FMAU]), was compared with acyclovir and idoxuridine in vitro against two strains of both herpes simplex virus type 1 (HSV-1) and HSV-2. Determinations of the 50% effective dose varied slightly with each strain and with the host cells employed. The 50% effective dose for FMAU and acyclovir against HSV-1 ranged from 0.1 microM to 0.5 to 0.6 microM in rabbit kidney cells and from 0.5 microM to 0.6 to 0.78 microM in Vero cells. Beginning 4 days post-inoculation, topical FMAU therapy given five times per day to rabbits with acute herpetic keratitis either suppressed or delayed the severity of corneal epithelial involvement, conjunctivitis, iritis, and corneal clouding. Responses to treatment with FMAU were similar to those obtained with acyclovir and significantly better than those attained with idoxuridine and vidarabine. At 30 to 40 days after the end of treatment, rabbit eyes were subjected to iontophoresis with epinephrine in an attempt to induce reactivation and enhance detection of previously latent HSV-1. Latent HSV-1 was detected in 67 to 92% of trigeminal ganglia in FMAU-treated animals and in 90% of placebo-treated animals.

Full text

PDF
808

Selected References

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

  1. Brigden D., Fiddian P., Rosling A. E., Ravenscroft T. Acyclovir - a review of the preclinical and early clinical data of a new antiherpes drug. Antiviral Res. 1981 Nov;1(4):203–212. doi: 10.1016/0166-3542(81)90011-5. [DOI] [PubMed] [Google Scholar]
  2. Coen D. M., Schaffer P. A. Two distinct loci confer resistance to acycloguanosine in herpes simplex virus type 1. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2265–2269. doi: 10.1073/pnas.77.4.2265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Collins P., Bauer D. J. Comparison of activity of herpes virus inhibitors. J Antimicrob Chemother. 1977 Mar;3 (Suppl A):73–81. doi: 10.1093/jac/3.suppl_a.73. [DOI] [PubMed] [Google Scholar]
  4. Crumpacker C. S., Schnipper L. E., Marlowe S. I., Kowalsky P. N., Hershey B. J., Levin M. J. Resistance to antiviral drugs of herpes simplex virus isolated from a patient treated with acyclovir. N Engl J Med. 1982 Feb 11;306(6):343–346. doi: 10.1056/NEJM198202113060606. [DOI] [PubMed] [Google Scholar]
  5. De Clercq E. Comparative efficacy of antiherpes drugs in different cell lines. Antimicrob Agents Chemother. 1982 Apr;21(4):661–663. doi: 10.1128/aac.21.4.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Elion G. B., Furman P. A., Fyfe J. A., de Miranda P., Beauchamp L., Schaeffer H. J. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5716–5720. doi: 10.1073/pnas.74.12.5716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Field H. J., Bell S. E., Elion G. B., Nash A. A., Wildy P. Effect of acycloguanosine treatment of acute and latent herpes simplex infections in mice. Antimicrob Agents Chemother. 1979 Apr;15(4):554–561. doi: 10.1128/aac.15.4.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Field H. J., Wildy P. Recurrent herpes simplex: the outlook for systemic antiviral agents. Br Med J (Clin Res Ed) 1981 Jun 6;282(6279):1821–1822. doi: 10.1136/bmj.282.6279.1821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kaufman H. E. Herpetic keratitis. Proctor Lecture. Invest Ophthalmol Vis Sci. 1978 Oct;17(10):941–957. [PubMed] [Google Scholar]
  10. Kwon B. S., Gangarosa L. P., Burch K. D., deBack J., Hill J. M. Induction of ocular herpes simplex virus shedding by iontophoresis of epinephrine into rabbit cornea. Invest Ophthalmol Vis Sci. 1981 Sep;21(3):442–449. [PubMed] [Google Scholar]
  11. Lopez C., Watanabe K. A., Fox J. J. 2'-fluoro-5-iodo-aracytosine, a potent and selective anti-herpesvirus agent. Antimicrob Agents Chemother. 1980 May;17(5):803–806. doi: 10.1128/aac.17.5.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nesburn A. B., Dunkel E. D., Trousdale M. D. Enhanced HSV recovery from neuronal tissues of latently infected rabbit. Proc Soc Exp Biol Med. 1980 Mar;163(3):398–401. doi: 10.3181/00379727-163-40785. [DOI] [PubMed] [Google Scholar]
  13. Smith K. O., Galloway K. S., Kennell W. L., Ogilvie K. K., Radatus B. K. A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2. Antimicrob Agents Chemother. 1982 Jul;22(1):55–61. doi: 10.1128/aac.22.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Trousdale M. D., Nesburn A. B., Miller C. A. Assessment of acyclovir on acute ocular infection induced by drug-resistant strains of HSV-1. Invest Ophthalmol Vis Sci. 1981 Feb;20(2):230–235. [PubMed] [Google Scholar]
  15. Trousdale M. D., Nesburn A. B., Watanabe K. A., Fox J. J. Evaluation of the antiherpetic activity of 2'-fluoro-5-iodo-ara-C in rabbit eyes and cell cultures. Invest Ophthalmol Vis Sci. 1981 Dec;21(6):826–832. [PubMed] [Google Scholar]
  16. Watanabe K. A., Reichman U., Hirota K., Lopez C., Fox J. J. Nucleosides. 110. Synthesis and antiherpes virus activity of some 2'-fluoro-2'-deoxyarabinofuranosylpyrimidine nucleosides. J Med Chem. 1979 Jan;22(1):21–24. doi: 10.1021/jm00187a005. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES