Wadsworth Center, New York State Department of Health, 120 New Scotland Ave., Albany, NY 12208, USA.
Antiviral Res. 2013 Mar;97(3):232-9. doi: 10.1016/j.antiviral.2012.12.012. Epub 2012 Dec 22.
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.
黄病毒甲基转移酶（MTase）依次对病毒 RNA 帽的 N-7 和 2'-O 位进行甲基化（GpppA-RNA→m(7)GpppA-RNA→m(7)GpppAm-RNA），使用 S-腺苷甲硫氨酸（SAM）作为甲基供体。我们在此报告了一系列新型核苷类似物的合成和生物学评价。其中两种化合物可以有效且竞争性地抑制 WNV MTase，IC50 值为微摩尔级，更重要的是，它们不抑制人 MTase。这些化合物还可以抑制细胞培养中的 WNV 复制。
