This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Leyssen, P.
Right arrow Articles by Neyts, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leyssen, P.
Right arrow Articles by Neyts, J.

 Previous Article  |  Next Article 

Journal of Virology, February 2005, p. 1943-1947, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1943-1947.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Predominant Mechanism by Which Ribavirin Exerts Its Antiviral Activity In Vitro against Flaviviruses and Paramyxoviruses Is Mediated by Inhibition of IMP Dehydrogenase

Pieter Leyssen, Jan Balzarini, Erik De Clercq, and Johan Neyts*

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium

Received 24 May 2004/ Accepted 20 September 2004

It is not yet clear to what extent depletion of intracellular GTP pools contributes to the antiviral activity of ribavirin. Therefore, the antiviral activities of (i) ribavirin, (ii) its 5-ethynyl analogue, 5-ethynyl-1-ß-D-ribofuranosylimidazole-4-carboxamide (EICAR), and (iii) mycophenolic acid (MPA) (a compound that inhibits only cellular IMP dehydrogenase activity) were studied on the replication of flaviviruses and paramyxoviruses. In addition, the effects of these three compounds on intracellular GTP pools were assessed. A linear correlation was observed over a broad concentration range between the antiviral activities of ribavirin, EICAR, and MPA and the effects of these compounds on GTP pool depletion. When the 50% effective concentrations (EC50s) for the antiviral activities of ribavirin, EICAR, and MPA were plotted against the respective EC50 values for GTP pool depletion, a linear correlation was calculated. These data provide compelling evidence that the predominant mechanism of action of ribavirin in vitro against flavi- and paramyxoviruses is based on inhibition of cellular IMP dehydrogenase activity.

* Corresponding author. Mailing address: Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: (32) 16-33.73.53. Fax: (32) 16-33.73.40. E-mail: johan.neyts{at}rega.kuleuven.ac.be.

Journal of Virology, February 2005, p. 1943-1947, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1943-1947.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Deng, L., Dai, P., Ciro, A., Smee, D. F., Djaballah, H., Shuman, S. (2007). Identification of Novel Antipoxviral Agents: Mitoxantrone Inhibits Vaccinia Virus Replication by Blocking Virion Assembly. J. Virol. 81: 13392-13402 [Abstract] [Full Text]  
  • Chang, K.-O., George, D. W. (2007). Interferons and Ribavirin Effectively Inhibit Norwalk Virus Replication in Replicon-Bearing Cells. J. Virol. 81: 12111-12118 [Abstract] [Full Text]  
  • Chung, D.-H., Sun, Y., Parker, W. B., Arterburn, J. B., Bartolucci, A., Jonsson, C. B. (2007). Ribavirin Reveals a Lethal Threshold of Allowable Mutation Frequency for Hantaan Virus. J. Virol. 81: 11722-11729 [Abstract] [Full Text]  
  • Noueiry, A. O., Olivo, P. D., Slomczynska, U., Zhou, Y., Buscher, B., Geiss, B., Engle, M., Roth, R. M., Chung, K. M., Samuel, M., Diamond, M. S. (2007). Identification of Novel Small-Molecule Inhibitors of West Nile Virus Infection. J. Virol. 81: 11992-12004 [Abstract] [Full Text]  
  • Kelley, J. B., Paschal, B. M. (2007). Hyperosmotic Stress Signaling to the Nucleus Disrupts the Ran Gradient and the Production of RanGTP. Mol. Biol. Cell 18: 4365-4376 [Abstract] [Full Text]  
  • Chevaliez, S., Brillet, R., Lazaro, E., Hezode, C., Pawlotsky, J.-M. (2007). Analysis of Ribavirin Mutagenicity in Human Hepatitis C Virus Infection. J. Virol. 81: 7732-7741 [Abstract] [Full Text]  
  • Barklis, E., Still, A., Sabri, M. I., Hirsch, A. J., Nikolich-Zugich, J., Brien, J., Dhenub, T. C., Scholz, I., Alfadhli, A. (2007). Sultam Thiourea Inhibition of West Nile Virus. Antimicrob. Agents Chemother. 51: 2642-2645 [Abstract] [Full Text]  
  • LIVONESI, M. C., DE SOUSA, R. L. M., BADRA, S. J., FIGUEIREDO, L. T.M. (2006). IN VITRO AND IN VIVO STUDIES OF RIBAVIRIN ACTION ON BRAZILIAN ORTHOBUNYAVIRUS. Am J Trop Med Hyg 75: 1011-1016 [Abstract] [Full Text]  
  • Takhampunya, R., Ubol, S., Houng, H.-S., Cameron, C. E., Padmanabhan, R. (2006). Inhibition of dengue virus replication by mycophenolic acid and ribavirin. J. Gen. Virol. 87: 1947-1952 [Abstract] [Full Text]  
  • Puig-Basagoiti, F., Tilgner, M., Forshey, B. M., Philpott, S. M., Espina, N. G., Wentworth, D. E., Goebel, S. J., Masters, P. S., Falgout, B., Ren, P., Ferguson, D. M., Shi, P.-Y. (2006). Triaryl pyrazoline compound inhibits flavivirus RNA replication.. Antimicrob. Agents Chemother. 50: 1320-1329 [Abstract] [Full Text]  
  • Chang, J., Nie, X., Gudima, S., Taylor, J. (2006). Action of Inhibitors on Accumulation of Processed Hepatitis Delta Virus RNAs.. J. Virol. 80: 3205-3214 [Abstract] [Full Text]  
  • Leyssen, P., De Clercq, E., Neyts, J. (2006). The Anti-Yellow Fever Virus Activity of Ribavirin Is Independent of Error-Prone Replication. Mol. Pharmacol. 69: 1461-1467 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»