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. 1975 Oct;8(4):463–467. doi: 10.1128/aac.8.4.463

Viral Keratitis-Inhibitory Effect of 9-β-d-Arabinofuranosylhypoxanthine 5′-Monophosphate

Robert W Sidwell 1, Lois B Allen 1, John H Huffman 1, Ganapathi R Revankar 1, Roland K Robins 1, Richard L Tolman 1
PMCID: PMC429372  PMID: 1190753

Abstract

Topical application of 9-β-d-arabinofuranosylhypoxanthine 5′-monophosphate (ara-HxMP) significantly inhibited the development of keratitis induced by types 1 and 2 herpes simplex virus and vaccinia virus in the eyes of rabbits. Parameters for evaluation of efficacy were infectivity (corneal opacity, lesion size, and type), Draize (erythema, conjunctival swelling, and discharge), and reduction in titer of recoverable virus from the eye. When the relative efficacy of the related compounds 9-β-d-arabinofuranosyladenine (ara-A), ara-A 5′-monophosphate (ara-AMP), and ara-Hx was determined against type 1 herpes simplex virus in a parallel experiment, the more water-soluble compounds (ara-HxMP, ara-AMP) were the most effective. The relative efficacy of ara-A was also determined against type 2 herpes and vaccinia virus-induced keratitis. Mortality in rabbits due to central nervous system involvement caused by types 1 and 2 herpes simplex virus was inhibited. Ara-HxMP was not discernibly toxic to the eye at concentrations of at least 20%; efficacy was still discernible with a 0.1% solution.

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Selected References

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

  1. Allen L. B., Huffman J. H., Revankar G. R., Tolman R. L., Simon L. N., Robins R. K., Sidwell R. W. Efficacy of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate in therapy of equine abortion virus-induced hepatitis in hamsters. Antimicrob Agents Chemother. 1975 Oct;8(4):474–478. doi: 10.1128/aac.8.4.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen L. B., Thompson J. M., Huffman J. H., Revankar G. R., Tolman R. L., Simon L. N., Robins R. K., Sidwell R. W. Inhibition of experimental deoxyribonucleic acid virus-induced encephalitis by 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate. Antimicrob Agents Chemother. 1975 Oct;8(4):468–473. doi: 10.1128/aac.8.4.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ch'ien L. T., Cannon N. J., Charamella L. J., Dismukes W. E., Whitley R. J., Buchanan R. A., Alford C. A., Jr Effect of adenine arabinoside on severe Herpesvirus hominis infections in man. J Infect Dis. 1973 Nov;128(5):658–663. doi: 10.1093/infdis/128.5.658. [DOI] [PubMed] [Google Scholar]
  4. KAUFMAN H. E., MARTOLA E. L., DOHLMAN C. H. Herpes simplex treatment with IDU and corticosteroids. Arch Ophthalmol. 1963 Apr;69:468–472. doi: 10.1001/archopht.1963.00960040474008. [DOI] [PubMed] [Google Scholar]
  5. KAUFMAN H., MARTOLA E. L., DOHLMAN C. Use of 5-iodo-2'-deoxyuridine (IDU) in treatment of herpes simplex keratitis. Arch Ophthalmol. 1962 Aug;68:235–239. doi: 10.1001/archopht.1962.00960030239015. [DOI] [PubMed] [Google Scholar]
  6. Kaufman H. E., Ellison E. D., Townsend W. M. The chemotherapy of herpes iritis with adenine arabinoside and cytarabine. Arch Ophthalmol. 1970 Dec;84(6):783–787. doi: 10.1001/archopht.1970.00990040785018. [DOI] [PubMed] [Google Scholar]
  7. Miyai K., Allen L. B., Huffman J. H., Sidwell R. W., Tolman R. L. Synthesis and anti-deoxyribonucleic acid virus activity of certain 9-beta-D-arabinofuranosyl-2-substituted adenine derivatives. J Med Chem. 1974 Feb;17(2):242–244. doi: 10.1021/jm00248a023. [DOI] [PubMed] [Google Scholar]
  8. Patterson A., Jones B. R. The management of ocular herpes. Trans Ophthalmol Soc U K. 1967;87:59–84. [PubMed] [Google Scholar]
  9. Pavan-Langston D., Dohlman C. H. A double blind clinical study of adenine arabinoside therapy of viral keratoconjunctivitis. Am J Ophthalmol. 1972 Jul;74(1):81–88. doi: 10.1016/0002-9394(72)91130-0. [DOI] [PubMed] [Google Scholar]
  10. Pavan-Langston D., Langston R. H., Geary P. A. Prophylaxis and therapy of experimental ocular herpes simplex. Comparison of idoxuridine, adenine arabinoside, and hypoxanthine arabinoside. Arch Ophthalmol. 1974 Nov;92(5):417–421. doi: 10.1001/archopht.1974.01010010429012. [DOI] [PubMed] [Google Scholar]
  11. Revankar G. R., Huffman J. H., Allen L. B., Sidwell R. W., Robins R. K., Tolman R. L. Synthesis and antiviral activity of certain 5'-monophosphates of 9-D-arabinofuranosyladenine and 9-D-arabinofuranosylhypoxanthine. J Med Chem. 1975 Jul;18(7):721–726. doi: 10.1021/jm00241a016. [DOI] [PubMed] [Google Scholar]
  12. Sidwell R. W., Allen L. B., Huffman J. H., Khwaja T. A., Tolman R. L., Robins R. K. Anti-DNA virus activity of the 5'-nucleotide and 3',5'-cyclic nucleotide of 9-beta-D-arabinofuranosyladenine. Chemotherapy. 1973;19(6):325–340. doi: 10.1159/000221473. [DOI] [PubMed] [Google Scholar]
  13. Sidwell R. W., Allen L. B., Khare G. P., Huffman J. H., Witkowski J. T., Simon L. N., Robins R. K. Effect of 1-beta-D-ribofuranosyl1-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) on herpes and vaccinia keratitis and encephalitis in laboratory animals. Antimicrob Agents Chemother. 1973 Feb;3(2):242–246. doi: 10.1128/aac.3.2.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Smith C. W., Sidwell R. W., Robins R. K., Tolman R. L. Azapurine nucleosides. 2. Synthesis and antiviral activity of 7-amino-3- -D-arabinofuranosyl-v-triazolo (4,5-d)pyrimidine and related nucleosides. J Med Chem. 1972 Sep;15(9):883–887. doi: 10.1021/jm00279a002. [DOI] [PubMed] [Google Scholar]

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