An antiviral thymidine analog
Brivudine is a thymidine analog and inhibitor of herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) viral replication.1,2 Following conversion to a 5'-triphosphate form by viral kinases, brivudine is incorporated into viral DNA, inhibiting viral DNA polymerases and inducing strand breakage.2 Brivudine (0.02-0.04 μg/ml) inhibits VZV replication in primary human fibroblasts and inhibits cytopathogenic effects of the KOS HSV-1 strain in a panel of cell lines (MIC50s = 0.007-0.4 μg/ml).1,3 It selectively inhibits cytopathogenicity induced by HSV-1 strains over HSV-2, vaccinia virus, vesicular stomatitis virus, or deoxythymidine kinase-deficient HSV-1 strains in E6SM cells (MIC50s = 0.02, 2-10, 7, >400, and 40 μg/ml, respectively).1 Brivudine (5 and 15 mg/kg twice per day) increases survival in a mouse model of disseminated HSV-1 infection.
1.De Clercq, E., Desgranges, C., Herdewijn, P., et al.Synthesis and antiviral activity of (E)-5-(2-bromovinyl)uracil and (E)-5-(2-bromovinyl)uridineJ. Med. Chem.29(2)213-217(1986) 2.Kulikowski, T.Structure-activity relationships and conformational features of antiherpetic pyrimidine and purine nucleoside analogues. A reviewPharm. World Sci.16(2)127-138(1994) 3.De Clercq, E., Descamps, J., Verhelst, G., et al.Antiviral activity of 5-(2-halogenovinyl)-2'-deoxyuridinesCurr. Chemother. Infect. Dis.21372-1374(1980)
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