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: Debra C Quenelle, Deborah J Collins, Terri L Rice, Aquilur Rahman, Robert Glazer
• Journal: Antiviral chemistry & chemotherapy (Antivir Chem Chemother) Vol. 22 Issue 3 Pg. 131-7 (Nov 17 2011) ISSN: 2040-2066 [Electronic] England
• PMID: 22095521 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antiviral Agents
• (north)-methanocarbathymidine
• Thymidine

Topics

• Administration, Oral
• Animals
• Antiviral Agents (administration & dosage, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Herpes Simplex (drug therapy, virology)
• Herpesvirus 2, Human (drug effects)
• Humans
• Mice
• Mice, Inbred BALB C
• Survival Rate
• Thymidine (administration & dosage, analogs & derivatives, pharmacology)