On the Mechanism of Anti-Herpes Action of E-5-(2-Bromovinyl)-2′-Deoxyuridine

BVDU [(E)-5-(2-bromovinyl)-2′-deoxyuridine) is an extremely potent and selective inhibitor of HSV 1 (herpes simplex virus type 1) and VZV (varicella zoster virus) replication: in primary rabbit kidney and/or human diploid fibroblast cultures these viruses are inhibited at a drug concentration of about 0.01 µg/ml (0.03 µM). The selective antiherpes activity of BVDU resides in a specific inhibition of viral DNA synthesis, which, in turn, depends on at least two factors: (i), phosphorylation of BVDU by the virus-encoded dThd (deoxythymidine) kinase and, (ii), inhibition of the virus-induced DNA polymerase by the resulting BVDUTP (BVDU 5′-triphosphate). Both viral enzymes appear to contribute to the selective antiherpes action of BVDU. While BVDUTP is a specific inhibitor of HSV 1 DNA polymerase, it remains to be established whether it can also serve as substrate for this enzyme. Unlike 5-halogenated deoxyuridines [i.e. IDU (5-iodo-2′-deoxyuridine)], BVDU does not induce the production of oncogenic RNA viruses in mouse (i.e. BALB/3T3) cell lines.