Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 Cytomegalovirus mutants resistant to ganciclovir and cidofovir differ in susceptibilities to synguanol and its 6-ether and 6-thioether derivatives.

Literature DB >> 24379208

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

Sunwen Chou¹, Gloria Komazin-Meredith, John D Williams, Terry L Bowlin.

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.

Entities: Chemical Disease Gene Species

Mesh：

Substances：

Year: 2013 PMID： 24379208 PMCID： PMC3957852 DOI： 10.1128/AAC.02544-13

Source DB: PubMed Journal: Antimicrob Agents Chemother ISSN： 0066-4804 Impact factor: 5.191

21 in total

1. Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus.

Authors: Sunwen Chou; Nell S Lurain; Kenneth D Thompson; Richard C Miner; W Lawrence Drew
Journal: J Infect Dis Date: 2003-06-16 Impact factor: 5.226

2. Phenotyping of cytomegalovirus drug resistance mutations by using recombinant viruses incorporating a reporter gene.

Authors: Sunwen Chou; Laura C Van Wechel; Heather M Lichy; Gail I Marousek
Journal: Antimicrob Agents Chemother Date: 2005-07 Impact factor: 5.191

3. The herpes simplex virus type 1 DNA polymerase gene: site of phosphonoacetic acid resistance mutation in strain Angelotti is highly conserved.

Authors: C W Knopf
Journal: J Gen Virol Date: 1987-05 Impact factor: 3.891

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

Authors: Fausto Baldanti; Antonella Sarasini; John C Drach; Jiri Zemlicka; Giuseppe Gerna
Journal: Antiviral Res Date: 2002-12 Impact factor: 5.970

5. Effective treatment of murine cytomegalovirus infections with methylenecyclopropane analogues of nucleosides.

Authors: R J Rybak; J Zemlicka; Y L Qiu; C B Hartline; E R Kern
Journal: Antiviral Res Date: 1999-10 Impact factor: 5.970

6. Oral activity of a methylenecyclopropane analog, cyclopropavir, in animal models for cytomegalovirus infections.

Authors: Earl R Kern; Deborah J Bidanset; Caroll B Hartline; Zhaohua Yan; Jiri Zemlicka; Debra C Quenelle
Journal: Antimicrob Agents Chemother Date: 2004-12 Impact factor: 5.191

7. A point mutation in the human cytomegalovirus DNA polymerase gene selected in vitro by cidofovir confers a slow replication phenotype in cell culture.

Authors: T Cihlar; M D Fuller; A S Mulato; J M Cherrington
Journal: Virology Date: 1998-09-01 Impact factor: 3.616

8. Characterization of drug resistance-associated mutations in the human cytomegalovirus DNA polymerase gene by using recombinant mutant viruses generated from overlapping DNA fragments.

Authors: T Cihlar; M D Fuller; J M Cherrington
Journal: J Virol Date: 1998-07 Impact factor: 5.103

9. Synthesis and antiviral activity of (Z)- and (E)-2,2-[bis(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines: second-generation methylenecyclopropane analogues of nucleosides.

Authors: Shaoman Zhou; Julie M Breitenbach; Katherine Z Borysko; John C Drach; Earl R Kern; Elizabeth Gullen; Yung-Chi Cheng; Jiri Zemlicka
Journal: J Med Chem Date: 2004-01-29 Impact factor: 7.446

10. Human cytomegalovirus UL97 kinase is involved in the mechanism of action of methylenecyclopropane analogs with 6-ether and -thioether substitutions.

Authors: Gloria Komazin-Meredith; Sunwen Chou; Mark N Prichard; Caroll B Hartline; Steven C Cardinale; Katelyn Comeau; John D Williams; Atiyya R Khan; Norton P Peet; Terry L Bowlin
Journal: Antimicrob Agents Chemother Date: 2013-10-21 Impact factor: 5.191

5 in total

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

1. Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus.

2. Phenotyping of cytomegalovirus drug resistance mutations by using recombinant viruses incorporating a reporter gene.

3. The herpes simplex virus type 1 DNA polymerase gene: site of phosphonoacetic acid resistance mutation in strain Angelotti is highly conserved.

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

5. Effective treatment of murine cytomegalovirus infections with methylenecyclopropane analogues of nucleosides.

6. Oral activity of a methylenecyclopropane analog, cyclopropavir, in animal models for cytomegalovirus infections.

7. A point mutation in the human cytomegalovirus DNA polymerase gene selected in vitro by cidofovir confers a slow replication phenotype in cell culture.

8. Characterization of drug resistance-associated mutations in the human cytomegalovirus DNA polymerase gene by using recombinant mutant viruses generated from overlapping DNA fragments.

9. Synthesis and antiviral activity of (Z)- and (E)-2,2-[bis(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines: second-generation methylenecyclopropane analogues of nucleosides.

10. Human cytomegalovirus UL97 kinase is involved in the mechanism of action of methylenecyclopropane analogs with 6-ether and -thioether substitutions.

Review 1. Current and potential treatments for ubiquitous but neglected herpesvirus infections.

2. TAOK3 phosphorylates the methylenecyclopropane nucleoside MBX 2168 to its monophosphate.

Review 3. Advances in the genotypic diagnosis of cytomegalovirus antiviral drug resistance.

4. Opposite effects of cytomegalovirus UL54 exonuclease domain mutations on acyclovir and cidofovir susceptibility.

Review 5. Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes.