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.
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: David I Bernstein; Fernando J Bravo; Derek A Pullum; Hui Shen; Mei Wang; Aquilur Rahman; Robert I Glazer; Rhonda D Cardin Journal: Antivir Chem Chemother Date: 2015-02