Z-isomers of 2-hydroxymethylcyclopropylidenemethyl adenine (synadenol) and guanine (synguanol) are active against ganciclovir- and foscarnet-resistant human cytomegalovirus UL97 mutants

Fausto Baldanti, Antonella Sarasini, John C. Drach, Jiri Zemlicka, Giuseppe Gerna

Research output: Contribution to journalArticlepeer-review

Abstract

Emergence of drug-resistant human cytomegalovirus (HCMV) strains is a substantial problem during treatment of HCMV infections in immunocompromised patients. The Z-isomers of 2-hydroxymethylcyclopropylidenemethyl adenine (synadenol) and guanine (synguanol) were previously shown to be potent inhibitors of AD169 and Towne HCMV reference strains and postulated to share a common phosphorylation pathway with ganciclovir (GCV) possibly involving the UL97-encoded phosphotransferase. Analysis of synadenol and synguanol susceptibility of a series of HCMV isolates from immunocompromised untreated patients and from patients with treatment failure due to the emergence of GCV- and foscarnet (PFA)-resistant HCMV strains demonstrated that synadenol and synguanol are potent inhibitors of clinical HCMV isolates and are highly effective against both GCV- and PFA-resistant isolates. These results together with those showing resistance of a UL97 knock-out HCMV mutant to GCV as well as synadenol and synguanol suggest the involvement of UL97 phosphotransferase in synadenol and synguanol anabolism but with a substrate specificity different from that of GCV.

Original languageEnglish
Pages (from-to)273-278
Number of pages6
JournalAntiviral Research
Volume56
Issue number3
DOIs
Publication statusPublished - Dec 1 2002

Keywords

  • Foscarnet-resistance
  • Ganciclovir-resistance
  • HCMV drug-susceptibility
  • HCMV UL97 phosphotransferase
  • Synadenol
  • Synguanol

ASJC Scopus subject areas

  • Virology
  • Pharmacology

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