title: Comparison of antiviral efficacies of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) and acyclovir against herpes simplex virus type 1 infections in mice.
abstract: 1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) and acyclovir were compared for their antiviral effects against herpes simplex virus type 1 (HSV-1) model infections in mice. Both drugs were not toxic to mice when they were administered orally by the same schedule used for therapeutic experiments. Brovavir was less toxic than acyclovir when injected by the intraperitoneal (i.p.) route. Marked efficacies of brovavir by either oral or i.p. administration were demonstrated in both experimental encephalitis and i.p. infection with HSV-1 WT-51 strain. Treatment with brovavir at a dose of 15 or 25 mg/kg twice daily resulted in increasing both survival rate and mean survival time of the infected mice. On the contrary, acyclovir showed only marginal effect against the experimental encephalitis. Survival rates of mice treated with brovavir were higher than those treated with acyclovir at corresponding doses with statistical significance. The superiority of brovavir was also found in the intracerebral infection with strain VR-3, a highly virulent strain for mice. Brovavir, but not acyclovir, at a dose of 200 mg/kg reduced the mortality. Acyclovir, however, were significantly effective in reducing mortality of systemically infected mice by both oral and i.p. administrations. The effective dose of acyclovir was lower than that of brovavir against i.p. infection with strain WT-51. Differences in mortality of strain VR-3-infected mice were statistically significant between acyclovir- and brovavir-treated groups.
authors.affiliation: Biology Laboratory, Yamasa Shoyu Co. Ltd., Choshi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Machida
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: N
authors.initials: N
authors.lastname: Ashida
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D001086:Arabinofuranosyluracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004660:Encephalitis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D006561:Herpes Simplex / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D051379:Mice; D018139:Simplexvirus / Q000187:drug effects*; D015996:Survival Rate
chemical_list: D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C031368:sorivudine; D000212:Acyclovir