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

@article{Chou2013CytomegalovirusMR,
  title={Cytomegalovirus Mutants Resistant to Ganciclovir and Cidofovir Differ in Susceptibilities to Synguanol and Its 6-Ether and 6-Thioether Derivatives},
  author={Sunwen Chou and Gloria Komazin-Meredith and John D. Williams and Terry L. Bowlin},
  journal={Antimicrobial Agents and Chemotherapy},
  year={2013},
  volume={58},
  pages={1809 - 1812}
}
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… 
View on ASMUSA
europepmc.org
10 Citations
Highly Influential Citations
1
Background Citations
2

10 Citations

Citation Type

Citation Type

Opposite effects of cytomegalovirus UL54 exonuclease domain mutations on acyclovir and cidofovir susceptibility.
  • S. Chou
  • Biology, Medicine
    Antiviral research
  • 2021
[Modern ethiotropic chemotherapy of human cytomegalovirus infection: clinical effectiveness, molecular mechanism of action, drug resistance, new trends and prospects. Part 2.]
TLDR
This review focused on viral proteins of interest as new potential targets and their inhibitors, such as the inhibitor of human CMV terminology, lethermovir, which showed great activity in the third phase of clinical trials, inhibitors of viral cyclin-dependent kinase (maribavir, cyclopropavir) and a number of compounds exhibiting anti-HCMV-activity, undergoing only preclinical trials in the experiment.
Advances in the genotypic diagnosis of cytomegalovirus antiviral drug resistance.
  • S. Chou
  • Biology
    Antiviral research
  • 2020
New therapies for human cytomegalovirus infections.
The discovery and development of filociclovir for the prevention and treatment of human cytomegalovirus-related disease.
TAOK3 phosphorylates the methylenecyclopropane nucleoside MBX 2168 to its monophosphate.
Novel bisthioether derivatives containing a 1,3,4-oxadiazole moiety: design, synthesis, antibacterial and nematocidal activities.
TLDR
Bioassay results showed that compound 4f exhibited the best antibacterial and nematocidal activities against rice bacterial leaf blight and citrus canker caused by Xanthomonas oryzae pv.
Current and Potential Treatments for Ubiquitous but Neglected Herpesvirus Infections
A comprehensive review of herpes virus drug discovery with an emphasis on the most recent advances in the field and their progression from early discovery to clinical development is presented. Small…
Highly Enantioselective Synthesis of Chiral Cyclopropyl Nucleosides via Catalytic Asymmetric Intermolecular Cyclopropanation.
An efficient route to construct chiral cyclopropyl purine nucleoside analogues has been established via the catalytic asymmetric Michael-initiated ring-closure reactions of α-purine acrylates with…
Mechanism of Activation of Anti-HCMV Nucleoside Analog MBX 2168

References

SHOWING 1-10 OF 24 REFERENCES
Cytomegalovirus UL97 Mutations Affecting Cyclopropavir and Ganciclovir Susceptibility
ABSTRACT Among the 7 most common UL97 mutations encountered in ganciclovir-resistant clinical cytomegalovirus isolates, the associated cyclopropavir cross-resistance varies from insignificant (L595S)…
Human Cytomegalovirus UL97 Kinase Is Involved in the Mechanism of Action of Methylenecyclopropane Analogs with 6-Ether and -Thioether Substitutions
TLDR
HCMV UL97 kinase is involved in the antiviral action of these MCPNs, but the in vitro selection of UL97-defective viruses suggests that their activity against more typical ganciclovir-resistant growth-competent UL97 mutants may be relatively preserved.
Cyclopropavir Susceptibility of Cytomegalovirus DNA Polymerase Mutants Selected after Antiviral Drug Exposure
ABSTRACT Human cytomegalovirus (CMV) UL54 DNA polymerase (pol) mutants with known patterns of resistance to current antivirals ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV) were tested for…
Effective treatment of murine cytomegalovirus infections with methylenecyclopropane analogues of nucleosides.
Accelerated Evolution of Maribavir Resistance in a Cytomegalovirus Exonuclease Domain II Mutant
TLDR
Findings are consistent with defective exonuclease activity of the pol D413A mutant T2294, leading to the accelerated evolution of UL97 mutations under MBV, which predict an MBV binding region overlapping the kinase ATP binding site and located upstream of known GCV resistance mutations.
Contrasting drug resistance phenotypes resulting from cytomegalovirus DNA polymerase mutations at the same exonuclease locus.
Antiviral Drug Resistance of Human Cytomegalovirus
TLDR
The virological and clinical data pertaining to HCMV antiviral drug resistance is summarized, which shows an evolving list of confirmed resistance mutations, although differences in interpretation have led to some confusion.
Z-isomers of 2-hydroxymethylcyclopropylidenemethyl adenine (synadenol) and guanine (synguanol) are active against ganciclovir- and foscarnet-resistant human cytomegalovirus UL97 mutants.
Oral Activity of a Methylenecyclopropane Analog, Cyclopropavir, in Animal Models for Cytomegalovirus Infections
TLDR
Oral treatment with 45 or 15 mg of CPV/kg initiated 24 h after infection was highly effective in reducing replication to undetectable levels in both models and was generally more effective than ganciclovir.
Phenotypic diversity of cytomegalovirus DNA polymerase gene variants observed after antiviral therapy.
  • S. Chou
  • Biology, Medicine
    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
  • 2011
...
1
2
3
...