Selective inhibition of the West Nile virus methyltransferase by nucleoside analogs

被引：47

作者：

Chen, Hui ^{[1
]}

Liu, Lihui ^{[1
]}

Jones, Susan A. ^{[1
]}

Banavali, Nilesh ^{[1
,2
]}

Kass, Jorden ^{[3
]}

Li, Zhong ^{[1
]}

Zhang, Jing ^{[1
]}

Kramer, Laura D. ^{[1
,2
]}

Ghosh, Arun K. ^{[3
]}

Li, Hongmin ^{[1
,2
]}

机构：

[1] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA

[2] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12201 USA

[3] Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA

来源：

ANTIVIRAL RESEARCH | 2013年 / 97卷 / 03期

关键词：

Flavivirus NS5; RNA cap methylation; West Nile virus; Methyltransferase; Antiviral development; RNA CAP; CRYSTAL-STRUCTURE; NS5; DOMAIN; METHYLATIONS; MOLECULES; CHARMM;

D O I：

10.1016/j.antiviral.2012.12.012

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：232 / 239

页数：8

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