Abstract
The flavivirus methyltransferase (MTase) sequentially methylates the N-7 and 2'-O positions of the viral RNA cap (GpppA-RNA→m(7)GpppA-RNA→m(7)GpppAm-RNA), using S-adenosyl-l-methionine (SAM) as a methyl donor. We report here the synthesis and biological evaluation of a series of novel nucleoside analogs. Two of these compounds can effectively and competitively inhibit the WNV MTase with IC50 values in micromolar range and, more importantly, do not inhibit human MTase. The compounds can also suppress the WNV replication in cell culture.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Down-Regulation
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Humans
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Methyltransferases / antagonists & inhibitors*
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Methyltransferases / genetics
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Methyltransferases / metabolism
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Nucleosides / chemical synthesis
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Nucleosides / pharmacology*
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Viral Proteins / antagonists & inhibitors*
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Viral Proteins / genetics
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Viral Proteins / metabolism
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Virus Replication / drug effects
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West Nile Fever / virology*
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West Nile virus / drug effects
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West Nile virus / enzymology*
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West Nile virus / genetics
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West Nile virus / physiology
Substances
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Nucleosides
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Viral Proteins
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Methyltransferases