Further evidence that ribavirin interacts with eIF4E

Abstract

This commentary discusses the recent reports in RNA by Yan and colleagues and Westman and colleagues of the apparent failure of ribavirin to bind to recombinant eIF4E and inhibit 7-methyl guanosine cap-dependent exogenous mRNA translation of cell extracts in vitro. Measuring binding by using affinity chromatography of matrix-immobilized proteins and by using protein emission fluorescence spectroscopy in the presence of nucleotide ligands, as well as limitations of using cell extracts for the assessment of mechanisms of mRNA translation are discussed. Possible reasons for the discordant findings of Yan and colleagues and Westman and colleagues are suggested, and direct observation of the specific binding of ribavirin to eIF4E by using mass spectrometry is presented.

Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy

“…142 The antiviral drug ribavirin can block the binding of eIF4E to mRNA. [143][144] The effects of this compound were examined in some patients with relapsed M4/M5 AML who were no longer eligible for chemotherapy. Although the number of patients in this preliminary trial were low (n ¼ 11), one complete and two partial responders were observed.…”

Targeting the translational apparatus to improve leukemia therapy: roles of the PI3K/PTEN/Akt/mTOR pathway

“…149 The antiviral drug ribavirin can block the binding of eIF4E to mRNA. 150,151 Thus, the effects of this compound were examined in some patients with relapsed M4/M5 AML who were no longer eligible for chemotherapy. Although the number of patients in this preliminary trial were low (n ¼ 11), one complete and two partial responders were observed.…”

Controlling Gene Expression through RNA Regulons: The Role of the Eukaryotic Translation Initiation Factor eIF4E

“…Ribavirin directly binds eIF4E as observed by NMR and mass spectrometry experiments. 31,34 Further, ribavirin impedes both eIF4E's function in 4E-SE mRNA export and in translation of eIF4E sensitive transcripts. 31 Consistent with its biochemical activity, ribavirin inhibits the growth promoting activities of eIF4E.…”

“…38 Ribavirin provides an alternative strategy to target eIF4E activity as it directly targets eIF4E via its mimicry of the m 7 G cap. 31,34 Thus, it is positioned to efficiently shut down the eIF4E regulon. However, only future clinical studies will determine its value in cancer therapies.…”