Novel Anticytomegalovirus Activity of Immunosuppressant Mizoribine and Its Synergism with Ganciclovir

@article{Kuramoto2010NovelAA,
  title={Novel Anticytomegalovirus Activity of Immunosuppressant Mizoribine and Its Synergism with Ganciclovir},
  author={Takashi Kuramoto and Tohru Daikoku and Yoshihiro Yoshida and Masaya Takemoto and Kumi Oshima and Yoshito Eizuru and Yoshinobu Kanda and Toshio Miyawaki and Kimiyasu Shiraki},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2010},
  volume={333},
  pages={816 - 821}
}
Cytomegalovirus (CMV) infection is a prominent infection in transplant recipients. The immunosuppressive drug mizoribine was shown to have anti-CMV activity in vitro and was reported to have an anti-CMV effect in renal transplantation. This study characterized the anti-CMV activity of mizoribine in vitro and its synergistic activity with ganciclovir. Mizoribine suppressed replication and at the EC50 for plaque inhibition of 12.0 μg/ml. Mizoribine and ganciclovir exerted a strong synergism in… 

Figures and Tables from this paper

The Efficacy of Mizoribine (Inosine Monophosphate Dehydrogenase Inhibitor) for ANCA-Associated Vasculitis with Hepatitis B Virus Carrier
TLDR
The effectiveness of mizoribine for the ANCA-associated vasculitis complicated with HBV-carrier is described, which was induced to clinical remission without reactivation of HBV.
Cyclophilin A as a target in the treatment of cytomegalovirus infections
TLDR
This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug, and links all the pathways mediated by cyclospora A, cytomegalovirus replication, and its encoded proteins.
Mizoribine versus mycophenolate mofetil or intravenous cyclophosphamide for induction treatment of active lupus nephritis
TLDR
MZR is well tolerated and has an effect similar to MMF in the induction therapy of active LN in comparison with mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC).
Do calcineurin inhibitors influence the serum concentrations of mizoribine
TLDR
The findings suggest the pharmacokinetics of MZR were well-described by 1-compartment model with first-order absorption and concomitant use of CNIs, e.g., Tac and CyA, may have no significant influence on the pharmacodynamics of MzR.
Comparative efficacy and safety of mizoribine and mycophenolate mofetil for treating systemic lupus erythematosus: a retrospective cohort study
TLDR
MZR may be a valuable option as an immunosuppressive agent for SLE, as well as MMF, and the adverse events of MZR, whose profile differs from MMF are comparable to or less than those of MMF.
The first year results of mizoribine/tacrolimus-based multitarget treatment for consecutive patients with lupus nephritis
TLDR
The results suggest that multitarget therapy using mizoribine opposed to MMF is highly safe and effective through 12 months and the therapy may enable faster dose reduction of concomitant glucocorticoids.
...
...

References

SHOWING 1-10 OF 45 REFERENCES
The Novel Immunosuppressive Agent Mycophenolate Mofetil Markedly Potentiates the Antiherpesvirus Activities of Acyclovir, Ganciclovir, and Penciclovir In Vitro and In Vivo
TLDR
MMF potentiated to some extent the growth retardation induced by GCV in young NMRI mice and may have clinical implications for those transplant recipients who receive both MMF and either ACV, GCV, or PCV and for the treatment of ACV-resistant mucocutaneous HSV infections.
Comparison of the effects of mizoribine with those of azathioprine, 6-mercaptopurine, and mycophenolic acid on T lymphocyte proliferation and purine ribonucleotide metabolism.
TLDR
It is concluded that mizoribine selectively inhibits guanine ribonucleotide formation in purified T cells, whereas the effect of 6MP appears to be more dependent on adenine rib onucleotide depletion.
Immunosuppressive dose of azathioprine inhibits replication of human cytomegalovirus in vitro
TLDR
Maintenance of an anti-HCMV dose of Aza in combination with CsA and Pred might establish not only satisfactory immunosuppression but also suppression of HCMV infection in transplant recipients.
Guanine ribonucleotide depletion inhibits T cell activation. Mechanism of action of the immunosuppressive drug mizoribine.
TLDR
Data indicate that mizoribine has an effect on T cell proliferation by a mechanism distinct from that of cyclosporine or corticosteroids, and therefore may be useful in combination immunosuppressive regimens.
Potentiation of antiherpetic activity of acyclovir by ribonucleotide reductase inhibition.
  • T. Spector, D. Averett, P. Furman
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1985
TLDR
Compound A723U and acyclovir (ACV) were found to exhibit mutual potentiation of their antiviral activities and subinhibitory concentrations of either compound greatly reduced the ED50 (median effective dose) of the other.
Case Report: Persistent cytomegalovirus (CMV) infection after haploidentical hematopoietic stem cell transplantation using in vivo alemtuzumab: emergence of resistant CMV due to mutations in the UL97 and UL54 genes
TLDR
In conclusion, the in vitro susceptibility assay as well as nucleotide sequence of clinical isolate is important to choose appropriate antiviral agents for patients who have persistent CMV reactivation after stem cell transplantation.
The use of mycophenolate mofetil in transplant recipients.
Acyclovir: mechanism of antiviral action and potentiation by ribonucleotide reductase inhibitors.
...
...