TY - JOUR
T1 - Inhibition of dengue virus replication by mycophenolic acid and ribavirin
AU - Takhampunya, Ratree
AU - Ubol, Sukathida
AU - Houng, Huo Shu
AU - Cameron, Craig E.
AU - Padmanabhan, Radhakrishnan
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
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U2 - 10.1099/vir.0.81655-0
DO - 10.1099/vir.0.81655-0
M3 - Article
C2 - 16760396
AN - SCOPUS:33745596104
VL - 87
SP - 1947
EP - 1952
JO - Journal of General Virology
JF - Journal of General Virology
SN - 0022-1317
IS - 7
ER -