title: Efficacy of N-methanocarbathymidine against genital herpes simplex virus type 2 shedding and infection in guinea pigs.
abstract: BACKGROUND
  Current approved nucleoside therapies for genital herpes simplex virus (HSV) infections are effective but improved therapies are needed for treatment of both acute and recurrent diseases.
  
  
  METHODS
  The effects of N-methanocarbathymidine were evaluated and compared to acyclovir using guinea pig models of acute and recurrent infection. For acute disease following intravaginal inoculation of 10(6 )pfu HSV-2 (MS strain), animals were treated intraperitoneally beginning 24 h post-infection, and the effects on disease severity, vaginal virus replication, subsequent recurrences, and latent virus loads were evaluated. For evaluation of recurrent infection, animals were treated for 21 days beginning 14 days after infection and disease recurrence and recurrent shedding were evaluated.
  
  
  RESULTS
  Treatment of the acute disease with N-methanocarbathymidine significantly reduced the severity of acute disease and decreased acute vaginal virus shedding more effectively than acyclovir. Significantly, none of the animals developed visible disease in the high-dose N-methanocarbathymidine group and this was the only group in which the number of days with recurrent virus shedding was reduced. Treatment of recurrent disease was equivalent to acyclovir when acyclovir was continuously supplied in the drinking water.
  
  
  CONCLUSIONS
  N-methanocarbathymidine was effective as therapy for acute and recurrent genital HSV-2 disease in the guinea pig models.
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA David.Bernstein@cchmc.org.
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Bravo
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Pullum
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: N & N Pharmaceuticals Inc., Rockville, MD, USA.
authors.forename: Aquilur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Glazer
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Cardin
mesh_terms: D000208:Acute Disease; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology*; D012008:Recurrence; D013936:Thymidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D017201:Virus Shedding / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C469995:(north)-methanocarbathymidine; D013936:Thymidine
keywords: Herpes simplex virus; N-methanocarbathymidine; genital herpes; recurrent herpes