Efficacy of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil against acute herpes simplex virus keratitis and the establishment of latency: comparison with acyclovir and bromovinyldeoxyuridine.
Four nucleoside analogues--acyclovir [9-(2-hydroxyethoxymethyl)guanine], bromovinyldeoxyuridine [(E)-5-(2-bromovinyl)-2-deoxyuridine], vinylarauracil 5-vinyl-1-beta-D-arabinofuranosyluracil and bromovinylarauracil [(E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil]--were compared in the therapy of acute keratitis induced in the rabbit cornea by inoculation of the KUPKA strain of herpes simplex virus type 1 (HSV-1). In comparison to placebo-treated animals, the drugs reduced the mean plaque counts in conjunctival swabs as follows: acyclovir to 0.16-1.73%, bromovinyldeoxyuridine to 0.02-0.25%, vinylarauracil to 0.55-5.96% and bromovinylarauracil to 0.12-3.39% of control values. Latency was established to a most limited extent in 1 or 2 out of 5 rabbits treated with vinylarauracil or bromovinylarauracil, respectively. One or 6 out of 84 or 98 explanted ganglion fragments (1.3 or 6%) were positive for HSV-1 as compared to 72 fragments out of 173 (43%) from placebo-treated rabbits. Acyclovir and bromovinyldeoxyuridine completely prevented latency.
D000208:Acute Disease; D000212:Acyclovir / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D007635:Keratitis, Dendritic / Q000188:drug therapy* / Q000382:microbiology; D011817:Rabbits; D018139:Simplexvirus / Q000187:drug effects / Q000502:physiology; D014529:Uridine / Q000031:analogs & derivatives*
D000998:Antiviral Agents; C020235:brivudine; D001086:Arabinofuranosyluracil; C048730:5-vinyl-1-arabinofuranosyluracil; C031368:sorivudine; D001973:Bromodeoxyuridine; D014529:Uridine; D000212:Acyclovir