Hydroxyurea enhances the activity of acyclovir and cidofovir against herpes simplex virus type 1 resistant strains harboring mutations in the thymidine kinase and/or the DNA polymerase genes.
Drug-resistant herpes simplex virus type 1 (HSV-1) recombinant strains harboring mutations in the thymidine kinase and/or the DNA polymerase genes were evaluated for their susceptibility to various antivirals in the presence of 25 microg/ml of hydroxyurea (HyU). The latter compound decreased the 50% inhibitory concentrations of acyclovir by 1.5-3.8-fold and that of cidofovir by 2.7-14.4-fold. However, HyU did not affect the susceptibilities of the various recombinant mutants to foscarnet. Hydroxyurea, a ribonucleotide reductase inhibitor, can increase the activity of nucleoside/nucleotide analogues against drug-resistant viruses.
Sergerie
Yan
Y
Research Center in Infectious Diseases of the CHUQ-CHUL, Québec City, QC, Canada. yan.sergerie@crchul.ulaval.ca
Boivin
Guy
G
D000212:Acyclovir / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D017245:Foscarnet / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology*; D012264:Ribonucleotide Reductases / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics*
D000998:Antiviral Agents; D004338:Drug Combinations; D063065:Organophosphonates; D017245:Foscarnet; D003596:Cytosine; D012264:Ribonucleotide Reductases; D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase; D000077404:Cidofovir; D000212:Acyclovir; D006918:Hydroxyurea