6-Methoxypurine arabinoside (ara-M) exhibits potent activity against varicella-zoster virus (VZV) as a result of ara-M's anabolism to the triphosphate of adenine arabinoside (ara-ATP) in VZV-infected cells. The adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) enhanced the formation of ara-ATP by inhibiting ara-M demethoxylation. In contrast, deoxycoformycin and coformycin, inhibitors of both adenosine deaminase and AMP deaminase, blocked the formation of ara-ATP and reversed the anti-VZV activity of ara-M. These results indicate that after the initial phosphorylation of ara-M by the VZV-coded thymidine kinase, the monophosphate is demethoxylated by AMP deaminase to form ara-IMP, which is converted to ara-ATP by the sequential actions of the cellular adenylosuccinate synthetase, adenylosuccinate lyase, and nucleotide kinases.
CITATION STYLE
De Miranda, P., Burnette, T. C., Biron, K. K., Miller, R. L., Averett, D. R., & Krenitsky, T. A. (1991). Anabolic pathway of 6-methoxypurine arabinoside in cells infected with varicella-zoster virus. Antimicrobial Agents and Chemotherapy, 35(10), 2121–2124. https://doi.org/10.1128/AAC.35.10.2121
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