Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine (BRL 39123) in animals.
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.
Boyd
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MR
Beecham Pharmaceuticals Research Division, Biosciences Research Centre, Great Burgh, Epsom, Surrey, England.
Bacon
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TH
Sutton
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D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006147:Guanine; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D010532:Peritoneal Diseases / Q000188:drug therapy / Q000382:microbiology; D012874:Skin Diseases, Infectious / Q000188:drug therapy / Q000382:microbiology
D000998:Antiviral Agents; C053539:penciclovir; D006147:Guanine; D000212:Acyclovir