1. Academic Validation
  2. A broad-spectrum antiviral molecule, QL47, selectively inhibits eukaryotic translation

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

  • J Biol Chem. 2020 Feb 7;295(6):1694-1703. doi: 10.1074/jbc.RA119.011132.
Mélissanne de Wispelaere 1 Margot Carocci 1 Dominique J Burri 1 William J Neidermyer Jr 1 Calla M Olson 2 Imme Roggenbach 1 Yanke Liang 2 Jinhua Wang 2 Sean P J Whelan 1 Nathanael S Gray 2 Priscilla L Yang 3
Affiliations

Affiliations

  • 1 Department of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115.
  • 2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215.
  • 3 Department of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115. Electronic address: priscilla_yang@hms.harvard.edu.
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.

Keywords

anticancer drug; antiviral agent; inhibition mechanism; small molecule; translation.

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