title: Efficacy of orally administered low dose N-methanocarbathymidine against lethal herpes simplex virus type-2 infections of mice.
abstract: BACKGROUND
  N-methanocarbathymidine (N-MCT) has previously been shown to be effective against lethal orthopoxvirus and herpes simplex virus type-1 infections in mice. In this investigation, the antiviral activity of N-MCT was assessed against herpes simplex virus type-2 (HSV-2) in BALB/c mice.
  
  
  METHODS
  BALB/c mice were infected intranasally with a lethal challenge dose of HSV-2. N-MCT was administered orally twice daily to mice using doses of 0.01 to 100 mg/kg to determine effects on survival and on viral replication in organ and central nervous system (CNS) samples.
  
  
  RESULTS
  N-MCT provided significant protection from mortality even when treatments were delayed until 3 days after viral infection. Viral replication in organ and CNS samples from N-MCT-treated mice was reduced below the limit of detection after 4 days of treatment.
  
  
  CONCLUSIONS
  These results indicated that low dose N-MCT treatment was more effective than acyclovir therapy. N-MCT may be effective against HSV disease in humans and is currently undergoing preclinical evaluation. In particular, its potential use as a combination therapy for HSV, with its differing metabolism from acyclovir, make it a promising compound to develop for human use.
authors.affiliation: The University of Alabama at Birmingham, Birmingham, AL, USA. DQuenelle@peds.uab.edu
authors.forename: Debra C
authors.initials: DC
authors.lastname: Quenelle
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Collins
authors.forename: Terri L
authors.initials: TL
authors.lastname: Rice
authors.forename: Aquilur
authors.initials: A
authors.lastname: Rahman
authors.forename: Robert
authors.initials: R
authors.lastname: Glazer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015996:Survival Rate; D013936:Thymidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; C469995:(north)-methanocarbathymidine; D013936:Thymidine