TY - JOUR T1 - Metabolism and Mode of Inhibition of Varicella-Zoster Virus by<span class="sc">l</span>-β-5-Bromovinyl-(2-hydroxymethyl)-(1,3-dioxolanyl)uracil Is Dependent on Viral Thymidine Kinase JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1109 LP - 1114 DO - 10.1124/mol.58.5.1109 VL - 58 IS - 5 AU - Ling Li AU - Ginger E. Dutschman AU - Elizabeth A. Gullen AU - Eisaku Tsujii AU - Susan P. Grill AU - Yongseok Choi AU - Chung K. Chu AU - Yung-chi Cheng Y1 - 2000/11/01 UR - http://molpharm.aspetjournals.org/content/58/5/1109.abstract N2 - A nonnaturally occurring l-configuration nucleoside analog,l-β-5-bromovinyl-(2-hydroxymethyl)-1,3-(dioxolanyl)uracil (l-BVOddU) selectively inhibited varicella-zoster virus growth in human embryonic lung (HEL) 299 cell culture with an EC50 of 0.055 μM, whereas no inhibition of CEM and HEL 299 cell growth or mitochondrial DNA synthesis was observed at concentrations up to 200 μM. l-BVOddU was phosphorylated by viral thymidine kinase but not by human cytosolic thymidine kinase, and the antiviral activity of this compound is dependent on the viral thymidine kinase. Unlike other d-configuration bromovinyl deoxyuridine analogs, such as E-5-(2-bromovinyl)-2′-deoxyuridine and 1-β-arabinofuranosyl-E-5-(2-bromovinyl)uracil, this compound was metabolized only to its monophosphate metabolite. The di- or triphosphate metabolites were not detected. This suggested that the inhibitory mechanism may be unique and different from other anti-herpesvirus nucleoside analogs. ER -