Distinct thymidine kinases encoded by cowpox virus and herpes simplex virus contribute significantly to the differential antiviral activity of nucleoside analogs

Antiviral Research
Mark N PrichardEarl R Kern

Abstract

Orthopoxviruses and herpesviruses are both large enveloped DNA viruses, yet these virus families exhibit very different susceptibilities to antiviral drugs. We investigated the activation of nucleoside analogs by the types I and II thymidine kinase (TK) homologs expressed by herpes simplex virus type 1 (HSV-1) and cowpox virus (CV). Antiviral activity against TK(-) and TK(+) strains of HSV-1 and CV was determined, and the ratio of the EC(50) values was used as a measurement of TK dependence. As to HSV-1, most of the selected compounds were markedly less effective against the TK(-) strains, suggesting that this enzyme was required for the activation of these nucleoside analogs. This differs from the results for CV where only idoxuridine and bromodeoxyuridine appeared to be activated, putatively by the type II TK expressed by this virus. These data confirm that the type II TK encoded by CV exhibits a more limited substrate specificity than the type I TK encoded by HSV-1. These data suggest that the inefficient activation of nucleoside analogs by the orthopoxvirus TK significantly limits their activity. Additional screening against orthopoxviruses will be required to identify nucleoside analogs that are efficiently activated by th...Continue Reading

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Citations

Sep 23, 2009·Antimicrobial Agents and Chemotherapy·Mark N PrichardEarl R Kern
Nov 26, 2008·Antimicrobial Agents and Chemotherapy·Earl R KernJohn A Secrist
Feb 28, 2007·Antimicrobial Agents and Chemotherapy·Mark N PrichardEarl R Kern
Mar 30, 2006·Antimicrobial Agents and Chemotherapy·Mark N PrichardEarl R Kern
Oct 16, 2013·Antimicrobial Agents and Chemotherapy·Sophie DuraffourRobert Snoeck
Aug 17, 2010·Antiviral Research·Mike BrayElaine Jagoda
Sep 12, 2006·The Journal of General Virology·Bernhard EhlersJochen Hentschke

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Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.