TY - JOUR
T1 - A broad-spectrum antiviral molecule, QL47, selectively inhibits eukaryotic translation
AU - De Wispelaere, Mélissanne
AU - Carocci, Margot
AU - Burri, Dominique J.
AU - Neidermyer, William J.
AU - Olson, Calla M.
AU - Roggenbach, Imme
AU - Liang, Yanke
AU - Wang, Jinhua
AU - Whelan, Sean P.J.
AU - Gray, Nathanael S.
AU - Yang, Priscilla L.
N1 - Funding Information:
This work was partially supported by National Institutes of Health Grants U54AI057159 NERP018 (to M. d. W., M. C., D. J. B., C. M. O., I. R., Y. L., J. W., N. S. G., and P. L. Y.), R01AI076442 (to M. d. W., M. C., D. J. B., I. R., and P. L. Y.), and R37 AI059371 (to W. J. N. and S. P. J. W.). N. S. G. is a founder, science advisory board member, and equity holder in Gatekeeper, Syros, Petra, C4, B2S, and Soltego. The Gray laboratory receives or has received research funding from Novartis, Takeda, Astellas, Taiho, Janssen, Kinogen, Voronoi, Her2llc, Deerfield, and Sanofi. The content is solely the responsi-bility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85079105494&partnerID=8YFLogxK
U2 - 10.1074/jbc.RA119.011132
DO - 10.1074/jbc.RA119.011132
M3 - Article
C2 - 31914414
AN - SCOPUS:85079105494
SN - 0021-9258
VL - 295
SP - 1694
EP - 1703
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -