Publication: Inhibition of dengue virus replication by mycophenolic acid and ribavirin
Issued Date
2006-07-01
Resource Type
ISSN
00221317
Other identifier(s)
2-s2.0-33745596104
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of General Virology. Vol.87, No.7 (2006), 1947-1952
Suggested Citation
Ratree Takhampunya, Sukathida Ubol, Huo Shu Houng, Craig E. Cameron, Radhakrishnan Padmanabhan Inhibition of dengue virus replication by mycophenolic acid and ribavirin. Journal of General Virology. Vol.87, No.7 (2006), 1947-1952. doi:10.1099/vir.0.81655-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/23320
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Title
Inhibition of dengue virus replication by mycophenolic acid and ribavirin
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. © 2006 SGM.