Evidence map›Paper›PMID 32571880›Full record

ArticleThe Journal of biological chemistry2020

Structural and functional conservation of the programmed -1 ribosomal frameshift signal of SARS coronavirus 2 (SARS-CoV-2).

Jamie A Kelly, Alexandra N Olson, Krishna Neupane, Sneha Munshi, Josue San Emeterio, Lois Pollack, Michael T Woodside, Jonathan D Dinman

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed
14.8field-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

155 citing papers in PubMed, 234 citations in OpenAlex.

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95 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Jamie A KellyDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA.ORCID 0000-0003-2416-2496
Alexandra N OlsonDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA.
Krishna NeupaneDepartment of Physics, University of Alberta, Edmonton, Alberta, Canada.
Sneha MunshiDepartment of Physics, University of Alberta, Edmonton, Alberta, Canada.
Josue San EmeterioSchool of Applied and Engineering Physics, Cornell University, Ithaca, New York, USA.
Lois PollackSchool of Applied and Engineering Physics, Cornell University, Ithaca, New York, USA lp26@cornell.edu mwoodsid@ualberta.ca dinman@umd.edu.ORCID 0000-0002-9366-4396
Michael T WoodsideDepartment of Physics, University of Alberta, Edmonton, Alberta, Canada lp26@cornell.edu mwoodsid@ualberta.ca dinman@umd.edu.
Jonathan D DinmanDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA lp26@cornell.edu mwoodsid@ualberta.ca dinman@umd.edu.ORCID 0000-0002-2402-9698
Cornell University · USUniversity of Alberta · CAUniversity of Maryland, College Park · US

Funding

X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Sean McSweeney · 2019 to 2026
$38.6M
Mechanisms of Virus Replication and Gene ExpressionT32AI051967 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI SIMON, ANNE ELIZABETH · 2002 to 2013
$1.8M
Graduate Training in VirologyT32AI125186 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI SIMON, ANNE ELIZABETH · 2016 to 2020
$1.3M
Regulation of programmed -1 ribosomal frameshifting by micro-RNAsR01GM117177 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI DINMAN, JONATHAN D · 2015 to 2018
$1.2M
A Simultaneous SAXS/WAXS Detector System for Solving Biological StructuresS10OD012331 · OD · STATE UNIVERSITY NEW YORK STONY BROOK · PI ALLAIRE, MARC · 2012 to 2012
$1.1M
NIAID NIH HHS T32 AI051967NIAID NIH HHS T32 AI125186NIGMS NIH HHS P30 GM133893NIGMS NIH HHS R01 GM117177NIH HHS S10 OD012331
6 · The paper itself

Abstract

Approximately 17 years after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, the world is currently facing the COVID-19 pandemic caused by SARS corona virus 2 (SARS-CoV-2). According to the most optimistic projections, it will take more than a year to develop a vaccine, so the best short-term strategy may lie in identifying virus-specific targets for small molecule-based interventions. All coronaviruses utilize a molecular mechanism called programmed -1 ribosomal frameshift (-1 PRF) to control the relative expression of their proteins. Previous analyses of SARS-CoV have revealed that it employs a structurally unique three-stemmed mRNA pseudoknot that stimulates high -1 PRF rates and that it also harbors a -1 PRF attenuation element. Altering -1 PRF activity impairs virus replication, suggesting that this activity may be therapeutically targeted. Here, we comparatively analyzed the SARS-CoV and SARS-CoV-2 frameshift signals. Structural and functional analyses revealed that both elements promote similar -1 PRF rates and that silent coding mutations in the slippery sites and in all three stems of the pseudoknot strongly ablate -1 PRF activity. We noted that the upstream attenuator hairpin activity is also functionally retained in both viruses, despite differences in the primary sequence in this region. Small-angle X-ray scattering analyses indicated that the pseudoknots in SARS-CoV and SARS-CoV-2 have the same conformation. Finally, a small molecule previously shown to bind the SARS-CoV pseudoknot and inhibit -1 PRF was similarly effective against -1 PRF in SARS-CoV-2, suggesting that such frameshift inhibitors may be promising lead compounds to combat the current COVID-19 pandemic.

Indexed as

Drug DesignBetacoronavirusCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentFrameshifting, RibosomalGene Expression Regulation, ViralHumansPandemicsPneumonia, ViralRNA, ViralSARS-CoV-2Virus ReplicationRNA, Viralcoronaviruscoronavirus disease 2019 (COVID-19)inhibitormRNA pseudoknotprogrammed −1 ribosomal frameshifting (−1 PRF)RNARNA structuresmall molecule inhibitor(+) ssRNAtranslationvirus

Identifiers

PMID32571880
PMCPMC7397099
OpenAlexW3036482641

What OpenQuestion holds

Textmetadata
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.