A broad-spectrum antiviral molecule, QL47, selectively inhibits eukaryotic translation

Mélissanne De Wispelaere, Margot Carocci, Dominique J. Burri, William J. Neidermyer, Calla M. Olson, Imme Roggenbach, Yanke Liang, Jinhua Wang, Sean P.J. Whelan, Nathanael S. Gray, Priscilla L. Yang

Research output: Contribution to journalArticle

Abstract

Small-molecule inhibitors of translation are critical tools to study the molecular mechanisms of protein synthesis. In this study, we sought to characterize how QL47, a host-targeted, small-molecule antiviral agent, inhibits steady-state viral protein expression. We demonstrate that this small molecule broadly inhibits both viral and host protein synthesis and targets a translation step specific to eukaryotic cells. We show that QL47 inhibits protein neosynthesis initiated by both canonical cap-driven and noncanonical initiation strategies, most likely by targeting an early step in translation elongation. Our findings thus establish QL47 as a new small-molecule inhibitor that can be utilized to probe the eukaryotic translation machinery and that can be further developed as a new therapeutic agent.

Original languageEnglish
Pages (from-to)1694-1703
Number of pages10
JournalJournal of Biological Chemistry
Volume295
Issue number6
DOIs
StatePublished - Jan 1 2020
Externally publishedYes

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  • Cite this

    De Wispelaere, M., Carocci, M., Burri, D. J., Neidermyer, W. J., Olson, C. M., Roggenbach, I., Liang, Y., Wang, J., Whelan, S. P. J., Gray, N. S., & Yang, P. L. (2020). A broad-spectrum antiviral molecule, QL47, selectively inhibits eukaryotic translation. Journal of Biological Chemistry, 295(6), 1694-1703. https://doi.org/10.1074/jbc.RA119.011132