Evaluation of anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]- guanine (A-5021) in mice.

Abstract

The anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guani ne (A-5021) was evaluated in murine cells and in several murine models of herpes simplex virus (HSV) infection. Against HSV type 1 (HSV-1), A-5021 was 15-30- and 30-60-fold more active, and against HSV type 2 (HSV-2), it was 2- and 8-fold more active than acyclovir and penciclovir in Balb/3T3 cells, respectively. When antiviral compounds were administered orally (once daily) to mice infected intraperitoneally with HSV-1 (Tomioka), A-5021 was more active than acyclovir or famciclovir in spite of its relatively low oral bioavailability. A-5021 was as active as penciclovir when the antiviral compounds were given intravenously (three times daily) to mice infected intraperitoneally with HSV-2 (186). In mice with a cutaneous HSV-1 (KOS) infection, three times daily oral therapy with A-5021 at 25 mg/kg per day produced more significant reduction in severity of skin lesions than equivalent treatment with acyclovir or famciclovir. In mice infected intracerebrally with HSV-1 (Tomioka), complete survival was observed in the group treated intravenously with A-5021 at 25 mg/kg per day (three times daily), while more than 50% of mice died in the groups treated intravenously with acyclovir of up to 100 mg/kg per day (three times daily). Moreover, A-5021 was more effective than acyclovir in clearing infectious virus from the brain. These findings demonstrate that A-5021 has potent anti-HSV activity in several murine models.

• Authors: S Iwayama, Y Ohmura, K Suzuki, N Ono, H Nakazawa, M Aoki, I Tanabe, T Sekiyama, T Tsuji, M Okunishi, K Yamanishi, Y Nishiyama
• Journal: Antiviral research (Antiviral Res) Vol. 42 Issue 2 Pg. 139-48 (Jun 1999) ISSN: 0166-3542 [Print] Netherlands
• PMID: 10389656 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 9-((cis-1,2-bis(hydroxymethyl)cycloprop-1-yl)methyl)guanine
• Antiviral Agents
• penciclovir
• Guanine
• Acyclovir

Topics

• 3T3 Cells
• Acyclovir (analogs & derivatives, pharmacology)
• Administration, Oral
• Animals
• Antiviral Agents (pharmacokinetics, pharmacology)
• Area Under Curve
• Disease Models, Animal
• Drug Evaluation
• Encephalitis (drug therapy, virology)
• Guanine (analogs & derivatives, pharmacokinetics, pharmacology)
• Herpes Simplex (drug therapy, mortality, virology)
• Injections, Intravenous
• Male
• Mice
• Mice, Inbred BALB C
• Microbial Sensitivity Tests
• Peritoneum (drug effects, pathology, virology)
• Simplexvirus (drug effects)
• Skin (drug effects, pathology, virology)
• Survival Rate