Efficacy of orally administered low dose N-methanocarbathymidine against lethalherpes simplex virus type-2 infections of mice.

摘要

BACKGROUND: N-methanocarbathymidine (N-MCT) has previously been shown to beeffective against lethal orthopoxvirus and herpes simplex virus type-1 infectionsin mice. In this investigation, the antiviral activity of N-MCT was assessedagainst herpes simplex virus type-2 (HSV-2) in BALB/c mice.METHODS: BALB/c mice were infected intranasally with a lethal challenge dose ofHSV-2. N-MCT was administered orally twice daily to mice using doses of 0.01 to100 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 whentreatments 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 ofdetection after 4 days of treatment.CONCLUSIONS: These results indicated that low dose N-MCT treatment was moreeffective than acyclovir therapy. N-MCT may be effective against HSV disease inhumans and is currently undergoing preclinical evaluation. In particular, itspotential use as a combination therapy for HSV, with its differing metabolismfrom acyclovir, make it a promising compound to develop for human use.