Correspondence

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 mM) and RBV (IC50=50?9±18 mM) inhibited DEN2 replication. Quantitative real-time RT-PCR of viral RNA and plaque assays of virions from DEN2-infected and MPA (10 mM)- and RBV (¢200 mM)-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 59 capping. Dengue viruses (DEN1–4), mosquito-borne members of the family Flaviviridae, are human pathogens of global signifi-cance. Of the 1 million annual cases of dengue haemor-rhagic fever/dengue shock syndrome, about 2–5 % are fatal. Currently, there is no vaccine or antiviral drug to treat DE