HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Takhampunya, R. Articles by Padmanabhan, R. Search for Related Content PubMed PubMed Citation Articles by Takhampunya, R. Articles by Padmanabhan, R. Agricola Articles by Takhampunya, R. Articles by Padmanabhan, R.

Inhibition of dengue virus replication by mycophenolic acid and ribavirin

¹ Department of Microbiology and Immunology, Georgetown University School of Medicine, 3900 Reservoir Road, Washington, DC 20057, USA
² Department of Microbiology, Faculty of Science, Mahidol University, 272 Rama VI Road, Bangkok 10400, Thailand
³ Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
⁴ Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA

Correspondence
Radhakrishnan Padmanabhan
rp55{at}georgetown.edu

Dengue viruses (DEN), mosquito-borne members of the family Flaviviridae, are human pathogens of global significance. The effects of mycophenolic acid (MPA) and ribavirin (RBV) on DEN replication in monkey kidney (LLC-MK2) cells were examined. MPA (IC₅₀=0.4±0.3 µM) and RBV (IC₅₀=50.9±18 µM) inhibited DEN2 replication. Quantitative real-time RT-PCR of viral RNA and plaque assays of virions from DEN2-infected and MPA (10 µM)- and RBV (200 µM)-treated cells showed a fivefold increase in defective viral RNA production by cells treated with each drug. Moreover, a dramatic reduction of intracellular viral replicase activity was seen by in vitro replicase assays. Guanosine reversed the inhibition of these compounds, suggesting that one mode of antiviral action of MPA and RBV is by inhibition of inosine monophosphate dehydrogenase and thereby depletion of the intracellular GTP pool. In addition, RBV may act by competing with guanine-nucleotide precursors in viral RNA translation, replication and 5' capping.

This article has been cited by other articles:

				J. D. Graci, K. Too, E. D. Smidansky, J. P. Edathil, E. W. Barr, D. A. Harki, J. E. Galarraga, J. M. Bollinger Jr., B. R. Peterson, D. Loakes, et al. Lethal Mutagenesis of Picornaviruses with N-6-Modified Purine Nucleoside Analogues Antimicrob. Agents Chemother., March 1, 2008; 52(3): 971 - 979. [Abstract] [Full Text] [PDF]

				A. O. Noueiry, P. D. Olivo, U. Slomczynska, Y. Zhou, B. Buscher, B. Geiss, M. Engle, R. M. Roth, K. M. Chung, M. Samuel, et al. Identification of Novel Small-Molecule Inhibitors of West Nile Virus Infection J. Virol., November 1, 2007; 81(21): 11992 - 12004. [Abstract] [Full Text] [PDF]