Evidence map›Paper›PMID 34185680›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Restriction of SARS-CoV-2 replication by targeting programmed -1 ribosomal frameshifting.

Yu Sun, Laura Abriola, Rachel O Niederer, Savannah F Pedersen, Mia M Alfajaro, Valter Silva Monteiro, Craig B Wilen, Ya-Chi Ho, Wendy V Gilbert, Yulia V Surovtseva and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
8.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 121 citations in OpenAlex.

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  11. Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication.Proceedings of the National Academy of Sciences of the United States of America · 2026
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29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Yu SunDepartment of Neuroscience, Yale University School of Medicine, New Haven, CT 06520.ORCID 0000-0003-4191-1786
Laura AbriolaYale Center for Molecular Discovery, Yale University, West Haven, CT 06516.ORCID 0000-0002-7304-6531
Rachel O NiedererDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520.
Savannah F PedersenDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520.ORCID 0000-0002-3091-903X
Mia M AlfajaroDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520.
Valter Silva MonteiroDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520.ORCID 0000-0003-1785-6713
Craig B WilenDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520.ORCID 0000-0003-2495-9403
Ya-Chi HoDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520.
Wendy V GilbertDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520.ORCID 0000-0003-2807-9657
Yulia V SurovtsevaYale Center for Molecular Discovery, Yale University, West Haven, CT 06516.
Brett D LindenbachDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520; brett.lindenbach@yale.edu junjie.guo@yale.edu.
Junjie U GuoDepartment of Neuroscience, Yale University School of Medicine, New Haven, CT 06520; brett.lindenbach@yale.edu junjie.guo@yale.edu.ORCID 0000-0001-8871-0055
Yale University · US

Funding

Molecular determinants of hepatitis C virus assemblyR01AI087925 · NIAID · YALE UNIVERSITY · PI LINDENBACH, BRETT D. · 2010 to 2020
$4.1M
Molecular and cellular determinants of RNA repeat-associated propertiesDP2GM132930 · NIGMS · YALE UNIVERSITY · PI GUO, JUNJIE · 2018 to 2018
$2.5M
Hepatitis C virus genome structure: dynamic roles in replication and infectivityR01AI131518 · NIAID · YALE UNIVERSITY · PI LINDENBACH, BRETT D., PYLE, ANNA MARIE · 2017 to 2020
$2.3M
NIAID NIH HHS R01 AI087925NIAID NIH HHS R01 AI131518NIGMS NIH HHS DP2 GM132930
6 · The paper itself

Abstract

Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a programmed -1 ribosomal frameshift (-1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in -1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a -1 PRF inhibitor for SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on -1 PRF of other betacoronaviruses. Consistent with the essential role of -1 PRF in viral gene expression, merafloxacin impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing proof-of-principle for targeting -1 PRF as a plausible and effective antiviral strategy for SARS-CoV-2 and other coronaviruses.

Indexed as

AnimalsAntiviral AgentsBetacoronavirusChlorocebus aethiopsFluoroquinolonesFrameshifting, RibosomalMutationNucleic Acid ConformationRNA, ViralSARS-CoV-2Vero CellsVirus ReplicationAntiviral AgentsCI 934FluoroquinolonesRNA, Viralcoronavirusmerafloxacinribosomal frameshiftingRNA pseudoknottranslation

Identifiers

PMID34185680
PMCPMC8256030
OpenAlexW3168084797

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.