IRES-targeting small molecule inhibits enterovirus 71 replication via allosteric stabilization of a ternary complex

Jesse Davila-Calderon; Neeraj N. Patwardhan; Liang-Yuan Chiu; Andrew Sugarman; Zhengguo Cai; Srinivasa R. Penutmutchu; Mei-Ling Li; Gary Brewer; Amanda E. Hargrove; Blanton S. Tolbert

doi:10.1038/s41467-020-18594-3

Nature Communications (Sep 2020)

IRES-targeting small molecule inhibits enterovirus 71 replication via allosteric stabilization of a ternary complex

Jesse Davila-Calderon,
Neeraj N. Patwardhan,
Liang-Yuan Chiu,
Andrew Sugarman,
Zhengguo Cai,
Srinivasa R. Penutmutchu,
Mei-Ling Li,
Gary Brewer,
Amanda E. Hargrove,
Blanton S. Tolbert

Affiliations

Jesse Davila-Calderon: Department of Chemistry, Case Western Reserve University
Neeraj N. Patwardhan: Department of Chemistry, Duke University
Liang-Yuan Chiu: Department of Chemistry, Case Western Reserve University
Andrew Sugarman: Department of Chemistry, Case Western Reserve University
Zhengguo Cai: Department of Chemistry, Duke University
Srinivasa R. Penutmutchu: Department of Chemistry, Case Western Reserve University
Mei-Ling Li: Department of Biochemistry and Molecular Biology, Rutgers Robert Wood Johnson Medical School
Gary Brewer: Department of Biochemistry and Molecular Biology, Rutgers Robert Wood Johnson Medical School
Amanda E. Hargrove: Department of Chemistry, Duke University
Blanton S. Tolbert: Department of Chemistry, Case Western Reserve University

DOI: https://doi.org/10.1038/s41467-020-18594-3
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 13

Abstract

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Human enterovirus 71 (EV71) contains an internal ribosome entry site (IRES) that promotes translation of viral RNA. Here the authors show that an antiviral small molecule DMA-135 binds to the EV71 IRES RNA, inducing conformational change and stabilizing a ternary complex to repress translation.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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