Evidence map›Paper›PMID 34426697›Full record

ArticleNature structural & molecular biology2021

Cryo-EM and antisense targeting of the 28-kDa frameshift stimulation element from the SARS-CoV-2 RNA genome.

Kaiming Zhang, Ivan N Zheludev, Rachel J Hagey, Raphael Haslecker, Yixuan J Hou, Rachael Kretsch, Grigore D Pintilie, Ramya Rangan, Wipapat Kladwang, Shanshan Li and 9 more

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

121 citing papers in PubMed, 1 synthesis or guideline pooled it.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Kaiming Zhang *Departments of Bioengineering, James H. Clark Center, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0414-4776
Ivan N Zheludev *Department of Biochemistry Stanford University, Stanford, CA, USA.
Rachel J Hagey *Departments of Medicine (Division of Gastroenterology and Hepatology) and Microbiology & Immunology, Stanford School of Medicine, Stanford, CA, USA.
Raphael HasleckerDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8001-9534
Yixuan J HouDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rachael KretschBiophysics Program, Stanford University, Stanford, CA, USA.
Grigore D PintilieDepartments of Bioengineering, James H. Clark Center, Stanford University, Stanford, CA, USA.
Ramya RanganBiophysics Program, Stanford University, Stanford, CA, USA.
Wipapat KladwangDepartment of Biochemistry Stanford University, Stanford, CA, USA.
Shanshan LiDepartments of Bioengineering, James H. Clark Center, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7041-5960
Marie Teng-Pei WuDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4972-6809
Edward A PhamDepartments of Medicine (Division of Gastroenterology and Hepatology) and Microbiology & Immunology, Stanford School of Medicine, Stanford, CA, USA.
Claire Bernardin-SouibguiDepartments of Medicine (Division of Gastroenterology and Hepatology) and Microbiology & Immunology, Stanford School of Medicine, Stanford, CA, USA.
Ralph S BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-6827-8701
Timothy P SheahanDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Victoria D'SouzaDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Jeffrey S GlennDepartments of Medicine (Division of Gastroenterology and Hepatology) and Microbiology & Immunology, Stanford School of Medicine, Stanford, CA, USA. jeffrey.glenn@stanford.edu.
Wah ChiuDepartments of Bioengineering, James H. Clark Center, Stanford University, Stanford, CA, USA. wahc@stanford.edu.ORCID http://orcid.org/0000-0002-8910-3078
Rhiju DasDepartment of Biochemistry Stanford University, Stanford, CA, USA. rhiju@stanford.edu.ORCID http://orcid.org/0000-0001-7497-0972

Funding

The Stanford-SLAC CryoEM Center supplementU24GM129541 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH, HEDMAN, BRITT · 2018 to 2023
$54.8M
Virology BSL4 CoreP01AI120943 · NIAID · WASHINGTON UNIVERSITY · PI Gaya K. Amarasinghe · 2016 to 2026
$30.2M
3 D ELECTRON MICROSCOPY OF MACROMOLECULES (5P41RR002250-27)P41GM103832 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH · 2012 to 2019
$15.1M
Unified Data Resource for Large Complexes Determined by Cryo-Electron MicroscopyR01GM079429 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH · 2007 to 2021
$11.6M
Next-generation computational/chemical methods for complex RNA structuresR35GM122579 · NIGMS · STANFORD UNIVERSITY · PI Rhiju Das · 2017 to 2026
$7.2M
TRAINING GRANT IN ACADEMIC GASTROENTEROLOGYT32DK007056 · NIDDK · STANFORD UNIVERSITY · PI Natalie J. Torok · 1986 to 2026
$6.5M
Molecular Interactions of HIV-1 with the Nuclear Pore ComplexR01AI148382 · NIAID · EMORY UNIVERSITY · PI MELIKIAN, GREGORY B, SARAFIANOS, STEFAN G · 2019 to 2022
$5.5M
Acquisition of a 300 kV Electron Microscope for Structural BiologyS10OD021600 · OD · STANFORD UNIVERSITY · PI CHIU, WAH · 2016 to 2016
$2.0M
Electron transfer activity of mitoNEET and regulation of energy metabolism in mitochondriaR15GM129564 · NIGMS · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI DING, HUANGEN · 2018 to 2018
$433k
NIAID NIH HHS 1R01AI13219101NIAID NIH HHS P01 AI120943NIAID NIH HHS R01 AI148382NIDDK NIH HHS T32 DK007056NIGMS NIH HHS P41 GM103832NIGMS NIH HHS R01 GM079429NIGMS NIH HHS R15 GM129564NIGMS NIH HHS R35 GM122579NIGMS NIH HHS U24 GM129541NIH HHS S10 OD021600
6 · The paper itself

Abstract

Drug discovery campaigns against COVID-19 are beginning to target the SARS-CoV-2 RNA genome. The highly conserved frameshift stimulation element (FSE), required for balanced expression of viral proteins, is a particularly attractive SARS-CoV-2 RNA target. Here we present a 6.9 Å resolution cryo-EM structure of the FSE (88 nucleotides, ~28 kDa), validated through an RNA nanostructure tagging method. The tertiary structure presents a topologically complex fold in which the 5' end is threaded through a ring formed inside a three-stem pseudoknot. Guided by this structure, we develop antisense oligonucleotides that impair FSE function in frameshifting assays and knock down SARS-CoV-2 virus replication in A549-ACE2 cells at 100 nM concentration.

Indexed as

A549 CellsAnimalsBase SequenceCell Line, TumorChlorocebus aethiopsCOVID-19Cryoelectron MicroscopyFrameshift MutationGenome, ViralHumansModels, MolecularNucleic Acid ConformationOligonucleotides, AntisenseResponse ElementsRNA, ViralSARS-CoV-2Oligonucleotides, AntisenseRNA, Viral

Identifiers

PMID34426697
PMCPMC8848339

What OpenQuestion holds

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Registered trials

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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.