Evidence map›Paper›PMID 34198328›Full record

ArticleThe Biochemical journal2021

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase.

Souradeep Basu, Tiffany Mak, Rachel Ulferts, Mary Wu, Tom Deegan, Ryo Fujisawa, Kang Wei Tan, Chew Theng Lim, Clovis Basier, Berta Canal and 11 more

Open access · hybridAbstract read
In one paragraph

Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.4field-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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. ACS medicinal chemistry letters · 2026
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  15. RSC medicinal chemistry · 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

21 authors at 3 institutions in 1 country.

Souradeep Basu *Cell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Tiffany Mak *Cell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Rachel UlfertsCell Biology of Infection Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Mary WuHigh Throughput Screening, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Tom DeeganThe MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Ryo FujisawaThe MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Kang Wei TanChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Chew Theng LimChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Clovis BasierCell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Berta CanalChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Joseph F CurranCell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Lucy S DruryChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Allison W McClureChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Emma L RobertsCell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Florian WeissmannChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Theresa U ZeisnerCell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Rupert BealeCell Biology of Infection Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Victoria H CowlingCentre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Michael HowellHigh Throughput Screening, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Karim LabibThe MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.ORCID 0000-0001-8861-379X
John F X DiffleyChromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.ORCID 0000-0001-5184-7680
The Francis Crick Institute · GBMRC Protein Phosphorylation and Ubiquitylation Unit · GBUniversity of Dundee · GB

Funding

Cancer Research UK 24558Medical Research Council MC_UU_00018/4Medical Research Council MC_UU_12016/13
6 · The paper itself

Abstract

The COVID-19 pandemic has presented itself as one of the most critical public health challenges of the century, with SARS-CoV-2 being the third member of the Coronaviridae family to cause a fatal disease in humans. There is currently only one antiviral compound, remdesivir, that can be used for the treatment of COVID-19. To identify additional potential therapeutics, we investigated the enzymatic proteins encoded in the SARS-CoV-2 genome. In this study, we focussed on the viral RNA cap methyltransferases, which play key roles in enabling viral protein translation and facilitating viral escape from the immune system. We expressed and purified both the guanine-N7 methyltransferase nsp14, and the nsp16 2'-O-methyltransferase with its activating cofactor, nsp10. We performed an in vitro high-throughput screen for inhibitors of nsp14 using a custom compound library of over 5000 pharmaceutical compounds that have previously been characterised in either clinical or basic research. We identified four compounds as potential inhibitors of nsp14, all of which also showed antiviral capacity in a cell-based model of SARS-CoV-2 infection. Three of the four compounds also exhibited synergistic effects on viral replication with remdesivir.

Indexed as

Drug Evaluation, PreclinicalAdenosine MonophosphateAlanineAnimalsAntiviral AgentsChlorobenzenesChlorocebus aethiopsEnzyme AssaysExoribonucleasesFluorescence Resonance Energy TransferHigh-Throughput Screening AssaysIndazolesIndenesIndolesMethyltransferasesNitriles(3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo(g)indazole-7-carboxylic acidAdenosine MonophosphateAlanineAntiviral AgentsChlorobenzenesExoribonucleasesinauzhinIndazolesIndenesIndoleslomeguatribMethyltransferasesNitrilesNSP14 protein, SARS-CoV-2NSP16 protein, SARS-CoV-2ORF1ab polyprotein, SARS-CoV-2PhenothiazinesPurinesremdesivirRNA CapsSmall Molecule LibrariesTrifluperidolViral Nonstructural ProteinsViral Regulatory and Accessory Proteinscoronaviruscovid-19methyltransferasemRNA cap

Identifiers

PMID34198328
PMCPMC8286817
OpenAlexW3177268895

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.