Evidence map›Paper›PMID 34328734›Full record

ArticleACS chemical biology2021

The SARS-CoV-2 Programmed -1 Ribosomal Frameshifting Element Crystal Structure Solved to 2.09 Å Using Chaperone-Assisted RNA Crystallography.

Christina Roman, Anna Lewicka, Deepak Koirala, Nan-Sheng Li, Joseph A Piccirilli

Open access · hybridAbstract read
In one paragraph

Article in ACS chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
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  11. Identifying the interactions conferring functional mechanical rigidity on RNase-resistant RNA from Zika virus.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
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  15. Heterogeneous and multiple conformational transition pathways between pseudoknots of the SARS-CoV-2 frameshift element.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
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  20. Novel Inhibitors of SARS-CoV-2 RNA Identified through Virtual Screening.Journal of chemical information and modeling · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Christina RomanDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, United States.
Anna LewickaDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, United States.
Deepak KoiralaDepartment of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), Baltimore, Maryland 21250, United States.ORCID 0000-0001-6424-3173
Nan-Sheng LiDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, United States.ORCID 0000-0002-1185-3688
Joseph A PiccirilliDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, United States.ORCID 0000-0002-0541-6270
University of Chicago · USUniversity of Maryland, Baltimore County · US

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI MALCOLM S. CAPEL · 2018 to 2026
$34.2M
Predoctoral Training Program in Chemistry & BiologyT32GM008720 · NIGMS · UNIVERSITY OF CHICAGO · PI PICCIRILLI, JOSEPH ANTHONY · 1999 to 2020
$4.7M
CHAPERONE-ASSISTED RNA CRYSTALLOGRAPHY - Resubmission 01R01GM102489 · NIGMS · UNIVERSITY OF CHICAGO · PI PICCIRILLI, JOSEPH ANTHONY · 2013 to 2021
$2.9M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Pixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8M
NCRR NIH HHS S10 RR029205NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM102489NIGMS NIH HHS T32 GM008720NIH HHS S10 OD021527
6 · The paper itself

Abstract

The programmed -1 ribosomal frameshifting element (PFSE) of SARS-CoV-2 is a well conserved structured RNA found in all coronaviruses' genomes. By adopting a pseudoknot structure in the presence of the ribosome, the PFSE promotes a ribosomal frameshifting event near the stop codon of the first open reading frame Orf1a during translation of the polyprotein pp1a. Frameshifting results in continuation of pp1a via a new open reading frame, Orf1b, that produces the longer pp1ab polyprotein. Polyproteins pp1a and pp1ab produce nonstructural proteins NSPs 1-10 and NSPs 1-16, respectively, which contribute vital functions during the viral life cycle and must be present in the proper stoichiometry. Both drugs and sequence alterations that affect the stability of the -1 programmed ribosomal frameshifting element disrupt the stoichiometry of the NSPs produced, which compromise viral replication. For this reason, the -1 programmed frameshifting element is considered a promising drug target. Using chaperone assisted RNA crystallography, we successfully crystallized and solved the three-dimensional structure of the PFSE. We observe a three-stem H-type pseudoknot structure with the three stems stacked in a vertical orientation stabilized by two triple base pairs at the stem 1/stem 2 and stem 1/stem 3 junctions. This structure provides a new conformation of PFSE distinct from the bent conformations inferred from midresolution cryo-EM models and provides a high-resolution framework for mechanistic investigations and structure-based drug design.

Indexed as

Molecular ChaperonesCrystallographyFrameshifting, RibosomalHumansModels, MolecularNucleic Acid ConformationRibosomesRNA, ViralSARS-CoV-2Viral ProteinsVirus ReplicationMolecular ChaperonesRNA, ViralViral Proteins

Identifiers

PMID34328734
PMCPMC8353986
OpenAlexW3183183657

What OpenQuestion holds

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LicenceCC BY
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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.