Evidence map›Paper›PMID 33963053›Full record

ArticleJournal of virology2021

Targeting the Conserved Stem Loop 2 Motif in the SARS-CoV-2 Genome.

Valeria Lulla, Michal P Wandel, Katarzyna J Bandyra, Rachel Ulferts, Mary Wu, Tom Dendooven, Xiaofei Yang, Nicole Doyle, Stephanie Oerum, Rupert Beale and 8 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.6field-weighted citation impact, top 5% 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

50 citing papers in PubMed, 62 citations in OpenAlex.

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  13. Tertiary folds of the SL5 RNA from the 5' proximal region of SARS-CoV-2 and related coronaviruses.Proceedings of the National Academy of Sciences of the United States of America · 2024
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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

18 authors at 7 institutions in 3 countries.

Valeria Lulla *Department of Pathology, Division of Virology, University of Cambridge, Cambridge, United Kingdom.
Michal P Wandel *MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Katarzyna J Bandyra *Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Rachel Ulferts *The Francis Crick Institute, London, United Kingdom.
Mary Wu *The Francis Crick Institute, London, United Kingdom.
Tom Dendooven *Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Xiaofei Yang *Department of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich, United Kingdom.
Nicole DoylePirbright Institute, Pirbright, Woking, United Kingdom.
Stephanie OerumCNRS-Université Paris Diderot, Institut de Biologie Physico-Chimique, Paris, France.
Rupert BealeThe Francis Crick Institute, London, United Kingdom.
Sara M O'RourkeUniversity of California at Santa Cruz, Santa Cruz, California, USA.
Felix RandowMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Helena J MaierPirbright Institute, Pirbright, Woking, United Kingdom.
William ScottUniversity of California at Santa Cruz, Santa Cruz, California, USA.
Yiliang DingDepartment of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich, United Kingdom.
Andrew E FirthDepartment of Pathology, Division of Virology, University of Cambridge, Cambridge, United Kingdom.
Kotryna BloznelyteDepartment of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Ben F LuisiDepartment of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
University of Cambridge · GBThe Francis Crick Institute · GBJohn Innes Centre · GBMRC Laboratory of Molecular Biology · GBThe Pirbright Institute · GBUniversity of California, Santa Cruz · USCentre National de la Recherche Scientifique · FR

Funding

Biotechnology and Biological Sciences Research Council BBS/E/I/00007034Biotechnology and Biological Sciences Research Council BBS/E/I/00007038Biotechnology and Biological Sciences Research Council BBS/E/I/COV07001Biotechnology and Biological Sciences Research Council BBS/E/J/000PR9788Medical Research Council MC_U105170648Wellcome Trust
6 · The paper itself

Abstract

RNA structural elements occur in numerous single-stranded positive-sense RNA viruses. The stem-loop 2 motif (s2m) is one such element with an unusually high degree of sequence conservation, being found in the 3' untranslated region (UTR) in the genomes of many astroviruses, some picornaviruses and noroviruses, and a variety of coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. The evolutionary conservation and its occurrence in all viral subgenomic transcripts imply a key role for s2m in the viral infection cycle. Our findings indicate that the element, while stably folded, can nonetheless be invaded and remodeled spontaneously by antisense oligonucleotides (ASOs) that initiate pairing in exposed loops and trigger efficient sequence-specific RNA cleavage in reporter assays. ASOs also act to inhibit replication in an astrovirus replicon model system in a sequence-specific, dose-dependent manner and inhibit SARS-CoV-2 replication in cell culture. Our results thus permit us to suggest that the s2m element is readily targeted by ASOs, which show promise as antiviral agents.

Indexed as

COVID-19Genome, ViralNucleotide MotifsRNA FoldingRNA, ViralVirus ReplicationAnimalsChlorocebus aethiopsHEK293 CellsHumansSARS-CoV-2Vero CellsRNA, ViralastroviruscoronavirusgapmerLNAplus-strand RNA viruss2mSARS-CoV-2therapeutic oligonucleotides

Identifiers

PMID33963053
PMCPMC8223950
OpenAlexW3158180440

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.