title: Selective inhibition of the West Nile virus methyltransferase by nucleoside analogs.
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.
authors.affiliation: Wadsworth Center, New York State Department of Health, 120 New Scotland Ave., Albany, NY 12208, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Lihui
authors.initials: L
authors.lastname: Liu
authors.forename: Susan A
authors.initials: SA
authors.lastname: Jones
authors.forename: Nilesh
authors.initials: N
authors.lastname: Banavali
authors.forename: Jorden
authors.initials: J
authors.lastname: Kass
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Laura D
authors.initials: LD
authors.lastname: Kramer
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Hongmin
authors.initials: H
authors.lastname: Li
mesh_terms: D015536:Down-Regulation; D006801:Humans; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009705:Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D014901:West Nile Fever / Q000821:virology*; D014902:West Nile virus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000502:physiology
chemical_list: D009705:Nucleosides; D014764:Viral Proteins; D008780:Methyltransferases