title: Cytomegalovirus mutants resistant to ganciclovir and cidofovir differ in susceptibilities to synguanol and its 6-ether and 6-thioether derivatives.
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.
authors.affiliation: Oregon Health and Science University and VA Medical Center, Portland, Oregon, USA.
authors.forename: Sunwen
authors.initials: S
authors.lastname: Chou
authors.forename: Gloria
authors.initials: G
authors.lastname: Komazin-Meredith
authors.forename: John D
authors.initials: JD
authors.lastname: Williams
authors.forename: Terry L
authors.initials: TL
authors.lastname: Bowlin
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003521:Cyclopropanes / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D017245:Foscarnet / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology*; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D063065:Organophosphonates / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; C000592664:MBX 1616; C000592663:MBX 2168; D063065:Organophosphonates; C470351:synguanol; D017245:Foscarnet; D006147:Guanine; D003596:Cytosine; C495219:cyclopropavir; D000077404:Cidofovir; D015774:Ganciclovir