Evidence map›Paper›PMID 32562705›Full record

ArticleAntiviral research2020

A library of nucleotide analogues terminate RNA synthesis catalyzed by polymerases of coronaviruses that cause SARS and COVID-19.

Steffen Jockusch, Chuanjuan Tao, Xiaoxu Li, Thomas K Anderson, Minchen Chien, Shiv Kumar, James J Russo, Robert N Kirchdoerfer, Jingyue Ju

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antiviral research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
16.5field-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

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.

  1. Pooled it
  2. Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in healthcare workers.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2023
    Trial
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19 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Steffen JockuschCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY, 10027, USA; Department of Chemistry, Columbia University, New York, NY, 10027, USA.
Chuanjuan TaoCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY, 10027, USA; Department of Chemical Engineering, Columbia University, New York, NY, 10027, USA.
Xiaoxu LiCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY, 10027, USA; Department of Chemical Engineering, Columbia University, New York, NY, 10027, USA.
Thomas K AndersonDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA; Institute of Molecular Virology, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Minchen ChienCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY, 10027, USA; Department of Chemical Engineering, Columbia University, New York, NY, 10027, USA.
Shiv KumarCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY, 10027, USA; Department of Chemical Engineering, Columbia University, New York, NY, 10027, USA.
James J RussoCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY, 10027, USA; Department of Chemical Engineering, Columbia University, New York, NY, 10027, USA.
Robert N KirchdoerferDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA; Institute of Molecular Virology, University of Wisconsin-Madison, Madison, WI, 53706, USA. Electronic address: rnkirchdoerf@wisc.edu.
Jingyue JuCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY, 10027, USA; Department of Chemical Engineering, Columbia University, New York, NY, 10027, USA; Department of Pharmacology, Columbia University, New York, NY, 10027, USA. Electronic address: dj222@columbia.edu.
New York Genome Center · USUniversity of Wisconsin–Madison · US

Funding

Structural Studies of the Corona Virus Life CycleR00AI123498 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KIRCHDOERFER, ROBERT N · 2020 to 2021
$719k
NIAID NIH HHS R00 AI123498
6 · The paper itself

Abstract

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 worldwide pandemic. We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine. We report here the evaluation of a library of nucleoside triphosphate analogues with a variety of structural and chemical features as inhibitors of the RdRps of SARS-CoV and SARS-CoV-2. These features include modifications on the sugar (2' or 3' modifications, carbocyclic, acyclic, or dideoxynucleotides) or on the base. The goal is to identify nucleotide analogues that not only terminate RNA synthesis catalyzed by these coronavirus RdRps, but also have the potential to resist the viruses' exonuclease activity. We examined these nucleotide analogues for their ability to be incorporated by the RdRps in the polymerase reaction and to prevent further incorporation. While all 11 molecules tested displayed incorporation, 6 exhibited immediate termination of the polymerase reaction (triphosphates of Carbovir, Ganciclovir, Stavudine and Entecavir; 3'-OMe-UTP and Biotin-16-dUTP), 2 showed delayed termination (Cidofovir diphosphate and 2'-OMe-UTP), and 3 did not terminate the polymerase reaction (2'-F-dUTP, 2'-NH

Indexed as

AbacavirAntiviral AgentsBetacoronavirusCidofovirCoronavirus InfectionsCOVID-19DideoxynucleosidesGanciclovirGuanineNucleotidesPandemicsPneumonia, ViralProdrugsRNA-Dependent RNA PolymeraseRNA, ViralSARS-CoV-2AbacavirAntiviral AgentsCidofovirDideoxynucleosidesentecavirGanciclovirGuanineNucleotidesProdrugsRNA-Dependent RNA PolymeraseRNA, ViralStavudineValganciclovirCOVID-19ExonucleaseNucleotide analoguesRNA-Dependent RNA polymeraseSARS-CoV-2

Identifiers

PMID32562705
PMCPMC7299870
OpenAlexW3036893309

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.