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. 1993 Nov;37(11):2478–2482. doi: 10.1128/aac.37.11.2478

Effects of phosphonylmethoxyalkyl derivatives studied with a murine model for abortion induced by equine herpesvirus 1.

A R Awan 1, H J Field 1
PMCID: PMC192413  PMID: 8285638

Abstract

(S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) were tested in a mouse model for equine herpesvirus 1-induced abortion. HPMPA, given twice daily, reduced virus replication, but the compound was embryotoxic. A single dose of HPMPC, however, reduced the incidence of abortion and transfer of virus to the fetuses while producing no obvious toxic effects.

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Selected References

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  1. Allen G. P., Bryans J. T. Molecular epizootiology, pathogenesis, and prophylaxis of equine herpesvirus-1 infections. Prog Vet Microbiol Immunol. 1986;2:78–144. [PubMed] [Google Scholar]
  2. 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]
  3. Aswell J. F., Allen G. P., Jamieson A. T., Campbell D. E., Gentry G. A. Antiviral activity of arabinosylthymine in herpesviral replication: mechanism of action in vivo and in vitro. Antimicrob Agents Chemother. 1977 Aug;12(2):243–254. doi: 10.1128/aac.12.2.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Awan A. R., Gibson J. S., Field H. J. A murine model for studying EHV-1-induced abortion. Res Vet Sci. 1991 Jul;51(1):94–99. doi: 10.1016/0034-5288(91)90038-p. [DOI] [PubMed] [Google Scholar]
  5. Bagust T. J., Pascoe R. R., Harden T. J. Studies on equine herpesviruses. 3. The incidence in Queensland of three different equine herpesvirus infections. Aust Vet J. 1972 Feb;48(2):47–53. doi: 10.1111/j.1751-0813.1972.tb05109.x. [DOI] [PubMed] [Google Scholar]
  6. De Castro L. M., Kern E. R., De Clercq E., Ghaffar A., Mayer E. P., Vogt P. E., Gangemi J. D. Phosphonylmethoxyalkyl purine and pyrimidine derivatives for treatment of opportunistic cytomegalovirus and herpes simplex virus infections in murine AIDS. Antiviral Res. 1991 Jul;16(1):101–114. doi: 10.1016/0166-3542(91)90062-v. [DOI] [PubMed] [Google Scholar]
  7. De Clercq E. Chemotherapy of the acquired immune deficiency syndrome (AIDS): acyclic nucleoside phosphonate analogues. Int J Immunopharmacol. 1991;13 (Suppl 1):91–98. doi: 10.1016/0192-0561(91)90130-y. [DOI] [PubMed] [Google Scholar]
  8. De Clercq E., Holý A. Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine in various models of herpes simplex virus infection in mice. Antimicrob Agents Chemother. 1991 Apr;35(4):701–706. doi: 10.1128/aac.35.4.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. De Clercq E., Holý A., Rosenberg I. Efficacy of phosphonylmethoxyalkyl derivatives of adenine in experimental herpes simplex virus and vaccinia virus infections in vivo. Antimicrob Agents Chemother. 1989 Feb;33(2):185–191. doi: 10.1128/aac.33.2.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. De Clercq E., Holý A., Rosenberg I., Sakuma T., Balzarini J., Maudgal P. C. A novel selective broad-spectrum anti-DNA virus agent. Nature. 1986 Oct 2;323(6087):464–467. doi: 10.1038/323464a0. [DOI] [PubMed] [Google Scholar]
  11. De Clercq E., Sakuma T., Baba M., Pauwels R., Balzarini J., Rosenberg I., Holý A. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antiviral Res. 1987 Dec;8(5-6):261–272. doi: 10.1016/s0166-3542(87)80004-9. [DOI] [PubMed] [Google Scholar]
  12. Field H. J., Awan A. R. Effective chemotherapy of equine herpesvirus 1 by phosphonylmethoxyalkyl derivatives of adenine demonstrated in a novel murine model for the disease. Antimicrob Agents Chemother. 1990 May;34(5):709–717. doi: 10.1128/aac.34.5.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Field H. J., Awan A. R., de la Fuente R. Isolation of equine herpesvirus-1 mutants in the presence of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine: demonstration of resistance in vitro and in vivo. Antiviral Res. 1991 Jul;16(1):29–39. doi: 10.1016/0166-3542(91)90056-w. [DOI] [PubMed] [Google Scholar]
  14. Gibson J. S., Slater J. D., Field H. J. The activity of (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC) against equine herpesvirus-1 (EHV-1) in cell cultures, mice and horses. Antiviral Res. 1992 Sep;19(3):219–232. doi: 10.1016/0166-3542(92)90081-f. [DOI] [PubMed] [Google Scholar]
  15. Gibson J. S., Slater J. D., Field H. J. The pathogenicity of Ab4p, the sequenced strain of equine herpesvirus-1, in specific pathogen-free foals. Virology. 1992 Jul;189(1):317–319. doi: 10.1016/0042-6822(92)90707-v. [DOI] [PubMed] [Google Scholar]
  16. Lee J. S., Mullaney S., Bronson R., Sharpe A. H., Jaenisch R., Balzarini J., De Clercq E., Ruprecht R. M. Transplacental antiretroviral therapy with 9-(2-phosphonylmethoxyethyl)adenine is embryotoxic in transgenic mice. J Acquir Immune Defic Syndr. 1991;4(9):833–838. [PubMed] [Google Scholar]
  17. Soike K. F., Huang J. L., Zhang J. Y., Bohm R., Hitchcock M. J., Martin J. C. Evaluation of infrequent dosing regimens with (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]-cytosine (S-HPMPC) on simian varicella infection in monkeys. Antiviral Res. 1991 Jul;16(1):17–28. doi: 10.1016/0166-3542(91)90055-v. [DOI] [PubMed] [Google Scholar]
  18. Stewart I. J. Granulated metrial gland cells in the mouse placenta. Placenta. 1990 May-Jun;11(3):263–275. doi: 10.1016/s0143-4004(05)80273-5. [DOI] [PubMed] [Google Scholar]
  19. Yang H., Datema R. Prolonged and potent therapeutic and prophylactic effects of (S)-1-[(3-hydroxy-2-phosphonylmethoxy)propyl]cytosine against herpes simplex virus type 2 infections in mice. Antimicrob Agents Chemother. 1991 Aug;35(8):1596–1600. doi: 10.1128/aac.35.8.1596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. de la Fuente R., Awan A. R., Field H. J. The acyclic nucleoside analogue penciclovir is a potent inhibitor of equine herpesvirus type 1 (EHV-1) in tissue culture and in a murine model. Antiviral Res. 1992 May;18(1):77–89. doi: 10.1016/0166-3542(92)90007-r. [DOI] [PubMed] [Google Scholar]

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