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. 1988 Mar;32(3):358–363. doi: 10.1128/aac.32.3.358

Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine (BRL 39123) in animals.

M R Boyd 1, T H Bacon 1, D Sutton 1
PMCID: PMC172176  PMID: 3364954

Abstract

The antiviral activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) was assessed in several animal models of herpes simplex virus (HSV) infection. BRL 39123 was as active as acyclovir (ACV) when applied topically to guinea pigs with a cutaneous HSV type 1 (HSV-1) infection and was also active topically in an HSV-2 genital infection. Before systemic administration to infected animals, BRL 39123 and ACV were administered orally and subcutaneously to mice, and the blood was assayed for each compound by high-pressure liquid chromatography. When given systemically to mice infected cutaneously with HSV-1, BRL 39123 was as active as ACV. In mice infected intranasally with HSV-1 or HSV-2, single daily subcutaneous doses of BRL 39123 were more effective than equivalent treatment with ACV, reflecting the more persistent activity seen in cell culture and a more stable triphosphate within the infected cell. When the compounds were supplied in drinking water for this infection, BRL 39123 and ACV had similar potencies against HSV-1, although ACV was more active against an HSV-2 infection than BRL 39123 was. In mice infected intraperitoneally with HSV-1, BRL 39123 was 10-fold more potent than ACV and a single dose of BRL 39123 reduced virus replication within the peritoneal cavity more effectively than 3 doses of ACV given 1, 5, and 20 h after infection. Although BRL 39123 failed to eradicate the virus from mice latently infected with HSV-1, treatment initiated 5 h after infection of the ear pinna reduced the numbers of mice that developed latent infections.

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Selected References

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

  1. Alenius S., Oberg B. Comparison of the therapeutic effects of five antiviral agents on cutaneous herpesvirus infection in guinea pigs. Arch Virol. 1978;58(4):277–288. doi: 10.1007/BF01317820. [DOI] [PubMed] [Google Scholar]
  2. Anderson J. R., Field H. J. The distribution of herpes simplex type 1 antigen in mouse central nervous system after different routes of inoculation. J Neurol Sci. 1983 Aug;60(2):181–195. doi: 10.1016/0022-510x(83)90061-8. [DOI] [PubMed] [Google Scholar]
  3. Blyth W. A., Harbour D. A., Hill T. J. Effect of acyclovir on recurrence of herpes simplex skin lesions in mice. J Gen Virol. 1980 Jun;48(Pt 2):417–419. doi: 10.1099/0022-1317-48-2-417. [DOI] [PubMed] [Google Scholar]
  4. Boyd M. R., Bacon T. H., Sutton D., Cole M. Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxy-methylbut-1-yl)guanine (BRL 39123) in cell culture. Antimicrob Agents Chemother. 1987 Aug;31(8):1238–1242. doi: 10.1128/aac.31.8.1238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Datema R., Ericson A. C., Field H. J., Larsson A., Stenberg K. Critical determinants of antiherpes efficacy of buciclovir and related acyclic guanosine analogs. Antiviral Res. 1987 Jul;7(6):303–316. doi: 10.1016/0166-3542(87)90013-1. [DOI] [PubMed] [Google Scholar]
  6. Field H. J., Anderson J. R., Efstathiou S. A quantitative study of the effects of several nucleoside analogues on established herpes encephalitis in mice. J Gen Virol. 1984 Apr;65(Pt 4):707–719. doi: 10.1099/0022-1317-65-4-707. [DOI] [PubMed] [Google Scholar]
  7. Fraser-Smith E. B., Smee D. F., Matthews T. R. Efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine against primary and recrudescent genital herpes simplex virus type 2 infections in guinea pigs. Antimicrob Agents Chemother. 1983 Dec;24(6):883–887. doi: 10.1128/aac.24.6.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Harbour D. A., Hill T. J., Blyth W. A. Acute and recurrent herpes simplex in several strains of mice. J Gen Virol. 1981 Jul;55(Pt 1):31–40. doi: 10.1099/0022-1317-55-1-31. [DOI] [PubMed] [Google Scholar]
  9. Harris S. R., Boyd M. R. The activity of iododeoxyuridine, adenine arabinoside, cytosine arabinoside, ribavirin and phosphonoacetic acid against herpes virus in the hairless mouse model. J Antimicrob Chemother. 1977 Mar;3 (Suppl A):91–98. doi: 10.1093/jac/3.suppl_a.91. [DOI] [PubMed] [Google Scholar]
  10. Hill T. J., Field H. J., Blyth W. A. Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. J Gen Virol. 1975 Sep;28(3):341–353. doi: 10.1099/0022-1317-28-3-341. [DOI] [PubMed] [Google Scholar]
  11. Klein R. J., Friedman-Kien A. E., DeStefano E. Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine. Antimicrob Agents Chemother. 1979 May;15(5):723–729. doi: 10.1128/aac.15.5.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kümel G., Kirchner H., Zawatzky R., Engler H., Schröder C. H., Kaerner H. C. Experimental infection of inbred mice with herpes simplex virus. V. Investigations with a virus strain non-lethal after peripheral infection. J Gen Virol. 1982 Dec;63(2):315–323. doi: 10.1099/0022-1317-63-2-315. [DOI] [PubMed] [Google Scholar]
  13. Larsson A., Stenberg K., Ericson A. C., Haglund U., Yisak W. A., Johansson N. G., Oberg B., Datema R. Mode of action, toxicity, pharmacokinetics, and efficacy of some new antiherpesvirus guanosine analogs related to buciclovir. Antimicrob Agents Chemother. 1986 Oct;30(4):598–605. doi: 10.1128/aac.30.4.598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schaeffer H. J., Beauchamp L., de Miranda P., Elion G. B., Bauer D. J., Collins P. 9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group. Nature. 1978 Apr 13;272(5654):583–585. doi: 10.1038/272583a0. [DOI] [PubMed] [Google Scholar]
  15. Smee D. F., Boehme R., Chernow M., Binko B. P., Matthews T. R. Intracellular metabolism and enzymatic phosphorylation of 9-(1,3-dihydroxy-2-propoxymethyl)guanine and acyclovir in herpes simplex virus-infected and uninfected cells. Biochem Pharmacol. 1985 Apr 1;34(7):1049–1056. doi: 10.1016/0006-2952(85)90608-2. [DOI] [PubMed] [Google Scholar]
  16. Stenberg K., Larsson A., Datema R. Metabolism and mode of action of (R)-9-(3,4-dihydroxybutyl)guanine in herpes simplex virus-infected vero cells. J Biol Chem. 1986 Feb 15;261(5):2134–2139. [PubMed] [Google Scholar]

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