Evidence map›Paper›PMID 34433083›Full record

ArticleCell reports2021

The nucleotide addition cycle of the SARS-CoV-2 polymerase.

Subhas Chandra Bera, Mona Seifert, Robert N Kirchdoerfer, Pauline van Nies, Yibulayin Wubulikasimu, Salina Quack, Flávia S Papini, Jamie J Arnold, Bruno Canard, Craig E Cameron and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

27 citing papers in PubMed, 34 citations in OpenAlex.

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  11. Nanopore tweezers show fractional-nucleotide translocation in sequence-dependent pausing by RNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 4 countries.

Subhas Chandra BeraJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.
Mona SeifertJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.
Robert N KirchdoerferDepartment of Biochemistry and Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Pauline van NiesJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.
Yibulayin WubulikasimuJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.
Salina QuackJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.
Flávia S PapiniJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.
Jamie J ArnoldDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Bruno CanardArchitecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, Polytech Case 925, 13009 Marseille, France.
Craig E CameronDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Martin DepkenDepartment of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, the Netherlands. Electronic address: s.m.depken@tudelft.nl.
David DulinJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany; Department of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1081, 1081 HV, Amsterdam, the Netherlands. Electronic address: d.dulin@vu.nl.
Friedrich-Alexander-Universität Erlangen-Nürnberg · DEUniversity of North Carolina at Chapel Hill · USArchitecture et Fonction des Macromolécules Biologiques · FRDelft University of Technology · NLUniversity of Wisconsin–Madison · USVrije Universiteit Amsterdam · NL

Funding

RNA DEPENDENT RNA POLYMERASE MECHANISMR01AI045818 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ARNOLD, JAMIE JON, CAMERON, CRAIG E. · 1999 to 2025
$7.5M
Coronavirus Genome ReplicationR01AI161841 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jamie Jon Arnold, CRAIG E. CAMERON · 2021 to 2026
$3.4M
Coronavirus RNA synthesis by multicomponent protein machinesR01AI158463 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KIRCHDOERFER, ROBERT N · 2020 to 2025
$2.1M
Structural Studies of the Corona Virus Life CycleR00AI123498 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KIRCHDOERFER, ROBERT N · 2020 to 2021
$719k
Structural Studies of the Coronavirus Life CycleK99AI123498 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI KIRCHDOERFER, ROBERT N · 2017 to 2018
$207k
NIAID NIH HHS K99 AI123498NIAID NIH HHS R00 AI123498NIAID NIH HHS R01 AI045818NIAID NIH HHS R01 AI158463NIAID NIH HHS R01 AI161841
6 · The paper itself

Abstract

Coronaviruses have evolved elaborate multisubunit machines to replicate and transcribe their genomes. Central to these machines are the RNA-dependent RNA polymerase subunit (nsp12) and its intimately associated cofactors (nsp7 and nsp8). We use a high-throughput magnetic-tweezers approach to develop a mechanochemical description of this core polymerase. The core polymerase exists in at least three catalytically distinct conformations, one being kinetically consistent with incorporation of incorrect nucleotides. We provide evidence that the RNA-dependent RNA polymerase (RdRp) uses a thermal ratchet instead of a power stroke to transition from the pre- to post-translocated state. Ultra-stable magnetic tweezers enable the direct observation of coronavirus polymerase deep and long-lived backtracking that is strongly stimulated by secondary structures in the template. The framework we present here elucidates one of the most important structure-dynamics-function relationships in human health today and will form the grounds for understanding the regulation of this complex.

Indexed as

Coronavirus RNA-Dependent RNA PolymeraseCOVID-19High-Throughput Screening AssaysHumansModels, MolecularMolecular ConformationNucleotidesRNA, ViralSARS-CoV-2Single Molecule ImagingViral Nonstructural ProteinsCoronavirus RNA-Dependent RNA PolymeraseNS8 protein, SARS-CoV-2NSP12 protein, SARS-CoV-2NucleotidesORF1ab polyprotein, SARS-CoV-2RNA, ViralViral Nonstructural Proteinsbacktrackinghigh-throughput/ultra-stable magnetic tweezersnucleotide addition cyclepolymerase mechanochemistrySARS-CoV-2 polymerasesingle-molecule biophysics

Identifiers

PMID34433083
PMCPMC8367775
OpenAlexW3194028163

What OpenQuestion holds

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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.