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Selective inhibition of the West Nile virus methyltransferase by nucleoside analogs. 2013
Hui Chen, and
Lihui Liu, and
Susan A Jones, and
Nilesh Banavali, and
Jorden Kass, and
Zhong Li, and
Jing Zhang, and
Laura D Kramer, and
Arun K Ghosh, and
Hongmin Li
Wadsworth Center, New York State Department of Health, 120 New Scotland Ave., Albany, NY 12208, USA.
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.
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