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Antimicrobial Agents and Chemotherapy, March 2005, p. 1081-1086, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.1081-1086.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Susceptibilities of Several Clinical Varicella-Zoster Virus (VZV) Isolates and Drug-Resistant VZV Strains to Bicyclic Furano Pyrimidine Nucleosides

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium,¹ Welsh School of Pharmacy, University of Wales College, Cardiff, United Kingdom²

Received 24 May 2004/ Returned for modification 19 July 2004/ Accepted 18 November 2004

Varicella-zoster virus (VZV) is responsible for primary infections as well as reactivations after latency in the dorsal root ganglia. The treatment of such infections is mandatory for immunocompromised patients and highly recommended for elderly patients with herpes zoster infections (also called zona or shingles). The treatment of choice is presently based on four molecules, acyclovir (ACV), valaciclovir, famciclovir, and (in Europe) brivudine (BVDU). We present here our data on the antiviral activity of a new class of potent and selective anti-VZV compounds, bicylic pyrimidine nucleoside analogues (BCNAs), against a broad variety of clinical isolates and different drug-resistant virus strains. The results show that the BCNAs are far more potent inhibitors than ACV and BVDU against clinical VZV isolates as well as the VZV reference strains Oka and YS. The BCNAs were not active against ACV- and BVDU-resistant VZV strains bearing mutations in the viral thymidine kinase gene but kept their inhibitory potential against virus strains with mutations in the VZV DNA polymerase gene. Mutant virus strains selected in the presence of the BCNAs were solely cross-resistant to drugs, such as ACV and BVDU, that depend for their antiviral action on metabolic activation by the viral thymidine kinase.

* Corresponding author. Mailing address: Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32-16-33.73.41. Fax: 32-16-33.73.40. E-mail; graciela.andrei{at}rega.kuleuven.ac.be

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