Inhibition of dengue virus replication by mycophenolic acid and ribavirin

Ratree Takhampunya, Sukathida Ubol, Huo Shu Houng, Craig E. Cameron, Radhakrishnan Padmanabhan

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1947-1952
Number of pages6
JournalJournal of General Virology
Volume87
Issue number7
DOIs
StatePublished - Jul 2006

All Science Journal Classification (ASJC) codes

  • Virology

Fingerprint Dive into the research topics of 'Inhibition of dengue virus replication by mycophenolic acid and ribavirin'. Together they form a unique fingerprint.

Cite this