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. 2014;58(3):1809-12.
doi: 10.1128/AAC.02544-13. Epub 2013 Dec 30.

Cytomegalovirus mutants resistant to ganciclovir and cidofovir differ in susceptibilities to synguanol and its 6-ether and 6-thioether derivatives

Sunwen Chou  1 , Gloria Komazin-Meredith, John D Williams, Terry L Bowlin
Affiliations

Cytomegalovirus mutants resistant to ganciclovir and cidofovir differ in susceptibilities to synguanol and its 6-ether and 6-thioether derivatives

Sunwen Chou et al. Antimicrob Agents Chemother. 2014.

Abstract

The methylenecyclopropane nucleoside (MCPN) analogs synguanol and its 6-alkoxy (MBX2168) and 6-alkylthio (MBX1616) derivatives retained good in vitro activities against several common ganciclovir-resistant UL97 kinase variants of human cytomegalovirus. Foscarnet-MCPN cross-resistance was observed among UL54 polymerase variants. UL54 exonuclease domain ganciclovir-cidofovir dual-resistant variants were remarkably more hypersensitive to these MCPNs than to cyclopropavir, with some 50% effective concentration ratios that were <0.1× the wild type. Different categories of MCPNs may have therapeutically exploitable mechanistic differences in viral DNA polymerase inhibition.

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Figures

FIG 1
FIG 1
Structures of methylenecyclopropane nucleoside analogs.
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