Abstract
The inhibition of herpes simplex virus type 1 plaque formation by acyclovir, bromovinyldeoxyuridine, 9-(3,4-dihydroxybutyl)guanine, and 9-(4-hydroxybutyl)guanine at different thymidine concentrations was analyzed in Lineweaver-Burk plots. Linear competitive patterns between thymidine and the nucleoside analogs were observed for the inhibition of herpes simplex virus type 1 plaque formation. A new constant, the reversal constant Kr, was introduced to describe the sensitivity in cell culture of an antiviral drug to the reversal of its viral activity by a metabolite (e.g., thymidine).
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Selected References
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- CLELAND W. W. The kinetics of enzyme-catalyzed reactions with two or more substrates or products. II. Inhibition: nomenclature and theory. Biochim Biophys Acta. 1963 Feb 12;67:173–187. doi: 10.1016/0006-3002(63)91815-8. [DOI] [PubMed] [Google Scholar]
- Cheng Y. C., Domin B. A., Sharma R. A., Bobek M. Antiviral action and cellular toxicity of four thymidine analogues: 5-ethyl-,5-vinyl-, 5-propyl-, and 5-allyl-2'- deoxyuridine. Antimicrob Agents Chemother. 1976 Jul;10(1):119–122. doi: 10.1128/aac.10.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Clercq E. Comparative efficacy of antiherpes drugs in different cell lines. Antimicrob Agents Chemother. 1982 Apr;21(4):661–663. doi: 10.1128/aac.21.4.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Clercq E., Descamps J., De Somer P., Barr P. J., Jones A. S., Walker R. T. (E)-5-(2-Bromovinyl)-2'-deoxyuridine: a potent and selective anti-herpes agent. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2947–2951. doi: 10.1073/pnas.76.6.2947. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Clercq E., Descamps J., Schmidt C. L., Mertes M. P. Antiviral activity of 5-methylthiomethyl-2'-deoxyuridine and other 5-substituted 2'-deoxyuridines. Biochem Pharmacol. 1979 Nov 15;28(22):3249–3254. doi: 10.1016/0006-2952(79)90117-5. [DOI] [PubMed] [Google Scholar]
- Fyfe J. A., Keller P. M., Furman P. A., Miller R. L., Elion G. B. Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine. J Biol Chem. 1978 Dec 25;253(24):8721–8727. [PubMed] [Google Scholar]
- Harmenberg J. Intracellular pools of thymidine reduce the antiviral action of acyclovir. Intervirology. 1983;20(1):48–51. doi: 10.1159/000149373. [DOI] [PubMed] [Google Scholar]
- Keller P. M., Fyfe J. A., Beauchamp L., Lubbers C. M., Furman P. A., Schaeffer H. J., Elion G. B. Enzymatic phosphorylation of acyclic nucleoside analogs and correlations with antiherpetic activities. Biochem Pharmacol. 1981 Nov 15;30(22):3071–3077. doi: 10.1016/0006-2952(81)90495-0. [DOI] [PubMed] [Google Scholar]