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. 1987 Mar;31(3):368–374. doi: 10.1128/aac.31.3.368

Demonstration of viral thymidine kinase inhibitor and its effect on deoxynucleotide metabolism in cells infected with herpes simplex virus.

L M Nutter, S P Grill, G E Dutschman, R A Sharma, M Bobek, Y C Cheng
PMCID: PMC174734  PMID: 3034143

Abstract

The thymidine analog 5'-ethynylthymidine was a potent inhibitor of herpes simplex virus type 1 (strain KOS)-induced thymidine kinase with a Ki value of 0.09 microM. 5'-Ethynylthymidine was less inhibitory against herpes simplex virus type 2 (strain 333)-induced thymidine kinase with a Ki of 0.38 microM and showed no inhibition against human cytosolic thymidine kinase under the conditions tested. The compound was effective against the altered thymidine kinase induced by acyclovir- and bromovinyldeoxyuridine-resistant virus variants. At 100 microM 5'-ethynylthymidine, the cellular pool size of dTTP in herpes simplex virus type 1-infected cells was 5% that of infected cells receiving no drug treatment, while there was no significant effect on the pool sizes of dATP, dGTP, and dCTP. There was a positive correlation between dTTP pools and the intracellular thymidine kinase activity of herpes simplex virus type 1-infected cells. When tested alone, 5'-ethynylthymidine exhibited no antiviral activity, but it antagonized the antiviral efficacy of five compounds which require viral thymidine kinase for their action.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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