Cytomegalovirus Mutants Resistant to Ganciclovir and Cidofovir Differ in Susceptibilities to Synguanol and Its 6-Ether and 6-Thioether Derivatives | Zendy

Sunwen Chou | Zendy; Gloria Komazin-Meredith | Zendy; John D. Williams | Zendy; Terry L. Bowlin | Zendy

Open Access

Cytomegalovirus Mutants Resistant to Ganciclovir and Cidofovir Differ in Susceptibilities to Synguanol and Its 6-Ether and 6-Thioether Derivatives

Author(s) -

Sunwen Chou,

Gloria Komazin-Meredith,

John D. Williams,

Terry L. Bowlin

Publication year - 2013

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.02544-13

Subject(s) - cidofovir , ganciclovir , foscarnet , virology , dna polymerase , human cytomegalovirus , biology , polymerase , mutant , cytomegalovirus , chemistry , dna , virus , herpesviridae , gene , biochemistry , viral disease

The methylenecyclopropane nucleoside (MCPN) analogs synguanol and its 6-alkoxy (MBX2168) and 6-alkylthio (MBX1616) derivatives retained goodin 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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