Xylotubercidin against herpes simplex virus type 2 in mice.
Of a series of newly synthesized derivatives of the pyrrolo[2,3-d]pyrimidine nucleosides tubercidin, toyocamycin, and sangivamycin, the xylosyl analog of tubercidin, xylotubercidin, exhibited the greatest potency and selectivity against herpes simplex virus type 2 (HSV-2) in vitro. At dosage regimens that were not toxic for the host, xylotubercidin proved efficacious in various HSV-2 animal model infections. When applied topically at 0.25, 0.5, or 1% in dimethyl sulfoxide or when administered systemically (intraperitoneally) at 12.5 or 25 mg/kg per day, xylotubercidin suppressed the development of herpetic skin lesions and the paralysis and mortality associated therewith in hairless mice inoculated intracutaneously with HSV-2. In this model, acyclovir was effective only if administered topically at 5 or 10% in dimethyl sulfoxide. When administered intraperitoneally over a dosage range of 10 to 50 mg/kg per day, xylotubercidin achieved a significant reduction in the mortality rate of mice infected intraperitoneally with HSV-2. Under the same conditions, acyclovir did not offer any protection even when administered at doses up to 250 mg/kg per day. Xylotubercidin thus appears to have considerable potential for both topical and systemic treatment of HSV-2 infections.
D000212:Acyclovir / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006561:Herpes Simplex / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D012263:Ribonucleosides / Q000627:therapeutic use*; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*
D000998:Antiviral Agents; D012263:Ribonucleosides; C050463:xylotubercidin; D014372:Tubercidin; D000212:Acyclovir