IMPORTANT NOTICE: We are putting the finishing touches to this new version of the repository; please bear with us! If you have any questions, please contact eprints.lincoln.ac.uk.

High frequency of spontaneous helicase-primase inhibitor (BAY 57-1293) drug-resistant variants in certain laboratory isolates of HSV-1.

Biswas, Subhajit and Swift, Mihaiela and Field, Hugh J. (2007) High frequency of spontaneous helicase-primase inhibitor (BAY 57-1293) drug-resistant variants in certain laboratory isolates of HSV-1. Antiviral Chemistry & Chemotherapy, 18 (1). pp. 13-23. ISSN 0956-3202

Full content URL: http://www.intmedpress.com/serveFile.cfm?sUID=7c9c...

Full text not available from this repository.

Item Type:Article
Item Status:Live Archive

Abstract

Herpes simplex virus (HSV) helicase-primase is the target for a new group of potent antivirals that show great promise in vivo. A claimed advantage of this class of compounds is the low rate of drug resistance, which is reported to occur at a lesser rate than acyclovir (ACV)-resistance in cell culture. We confirmed that BAY 57-1293 is highly active against HSV-1 and superior to ACV when tested in Vero cells. Notably, drug resistance was detected in laboratory working stocks in two different strains of HSV at 10(-4) to 10(-5) and there was evidence that the resistant variants were present in the virus population before the selection was applied. Plaque-purified clones obtained from the parental viruses showed a lower level of resistance selection in the presence of drug (10-6) and this value is similar to published reports. In the case of HSV-1 SC16, no difference was observed between a working stock and a plaque-pure clone in the rate of resistance to the nucleoside analogue ACV. The working stocks were found to contain variants with resistance to BAY 57-1293 ranging from approximately 15-fold to 4,000-fold suggesting that these viruses have the potential to subvert effective therapy. Sequence analysis of HSV-1 helicase protein showed that most of the amino acid substitutions in the variants described in this study tallied with published results, with some interesting exceptions in the case of HSV-1 strain PDK. Resistant variants did not readily revert to a sensitive phenotype in the absence of the inhibitor and representative BAY 57-1293-resistant variants were cross-resistant to an alternative helicase-primase inhibitor, BILS 22 BS. Variants resistant to BAY 57-1293 retained sensitivity to the nucleoside analogue, ACV.

Keywords:Virus evolution, cell culture, Virus plaque assay, DNA virus, Antivirals
Subjects:C Biological Sciences > C540 Virology
C Biological Sciences > C521 Medical Microbiology
Divisions:College of Science > School of Life Sciences
ID Code:9377
Deposited On:10 May 2013 09:24

Repository Staff Only: item control page