A Broad-Spectrum Antiviral Molecule, QL47, Selectively Inhibits Eukaryotic Translation

Authors

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

Publication Date

2-7-2020

Journal

Journal of Biological Chemistry

DOI

10.1074/jbc.RA119.011132

PMID

31914414

PMCID

PMC7008383

PubMedCentral® Posted Date

12-30-2019

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Antiviral Agents, Cell Line, HEK293 Cells, Humans, Protein Biosynthesis, Proteins, Small Molecule Libraries, Viral Proteins, Virus Diseases, Viruses, translation, small molecule, inhibition mechanism, antiviral agent, anticancer drug

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.

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