Evidence map›Paper›PMID 34198326›Full record

ArticleThe Biochemical journal2021

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp14/nsp10 exoribonuclease.

Berta Canal, Allison W McClure, Joseph F Curran, Mary Wu, Rachel Ulferts, Florian Weissmann, Jingkun Zeng, Agustina P Bertolin, Jennifer C Milligan, Souradeep Basu and 9 more

Abstract 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 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
–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

36 citing papers in PubMed.

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  7. Au(I)-based compounds inhibit nsp14/nsp10 and nsp13 (helicase) to exert anti-SARS-CoV-2 properties.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2025
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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

19 authors.

Berta Canal *Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Allison W McClure *Chromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Joseph F Curran *Cell Cycle 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.
Rachel UlfertsCell Biology of Infection 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.
Jingkun ZengChromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Agustina P BertolinChromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Jennifer C MilliganChromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Souradeep BasuCell 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.
Tom D 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.
Emma L RobertsCell Cycle 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.
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
Rupert BealeCell Biology of Infection Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Michael HowellHigh Throughput Screening, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
John F X DiffleyChromosome Replication Laboratory, the Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.ORCID 0000-0001-5184-7680

Funding

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

Abstract

SARS-CoV-2 is a coronavirus that emerged in 2019 and rapidly spread across the world causing a deadly pandemic with tremendous social and economic costs. Healthcare systems worldwide are under great pressure, and there is an urgent need for effective antiviral treatments. The only currently approved antiviral treatment for COVID-19 is remdesivir, an inhibitor of viral genome replication. SARS-CoV-2 proliferation relies on the enzymatic activities of the non-structural proteins (nsp), which makes them interesting targets for the development of new antiviral treatments. With the aim to identify novel SARS-CoV-2 antivirals, we have purified the exoribonuclease/methyltransferase (nsp14) and its cofactor (nsp10) and developed biochemical assays compatible with high-throughput approaches to screen for exoribonuclease inhibitors. We have screened a library of over 5000 commercial compounds and identified patulin and aurintricarboxylic acid (ATA) as inhibitors of nsp14 exoribonuclease in vitro. We found that patulin and ATA inhibit replication of SARS-CoV-2 in a VERO E6 cell-culture model. These two new antiviral compounds will be valuable tools for further coronavirus research as well as potentially contributing to new therapeutic opportunities for COVID-19.

Indexed as

Drug Evaluation, PreclinicalAnimalsAntiviral AgentsAurintricarboxylic AcidChlorocebus aethiopsEnzyme AssaysExoribonucleasesFluorescenceHigh-Throughput Screening AssaysPatulinReproducibility of ResultsSARS-CoV-2Small Molecule LibrariesVero CellsViral Nonstructural ProteinsViral Regulatory and Accessory ProteinsAntiviral AgentsAurintricarboxylic AcidExoribonucleasesNSP14 protein, SARS-CoV-2ORF1ab polyprotein, SARS-CoV-2PatulinSmall Molecule LibrariesViral Nonstructural ProteinsViral Regulatory and Accessory Proteins

Identifiers

PMID34198326
PMCPMC8286829

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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.