Selective inhibition of the West Nile virus methyltransferase by nucleoside analogs

Hui Chen, Lihui Liu, Susan A. Jones, Nilesh Banavali, Jorden Kass, Zhong Li, Jing Zhang, Laura D. Kramer, Arun K. Ghosh, Hongmin Li

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The flavivirus methyltransferase (MTase) sequentially methylates the N-7 and 2'-O positions of the viral RNA cap (GpppA-RNA→m7GpppA-RNA→m7GpppAm-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.

Original languageEnglish (US)
Pages (from-to)232-239
Number of pages8
JournalAntiviral Research
Volume97
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

Keywords

  • Antiviral development
  • Flavivirus NS5
  • Methyltransferase
  • RNA cap methylation
  • West Nile virus

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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