Evidence map›Paper›PMID 34198323›Full record

ArticleThe Biochemical journal2021

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp12/7/8 RNA-dependent RNA polymerase.

Agustina P Bertolin, Florian Weissmann, Jingkun Zeng, Viktor Posse, Jennifer C Milligan, Berta Canal, Rachel Ulferts, Mary Wu, Lucy S Drury, Michael Howell and 2 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 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Interference of small compounds and MgScientific reports · 2024
    Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. The origins of COVID-19 pandemic: A brief overview.Transboundary and emerging diseases · 2022
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. An all-out assault on SARS-CoV-2 replication.The Biochemical journal · 2021
    Article
  16. Article
  17. Article
  18. Article
  19. Article
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

12 authors at 1 institution in 1 country.

Agustina P Bertolin *Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Florian Weissmann *Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Jingkun Zeng *Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.
Viktor PosseChromosome 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.
Berta CanalChromosome Replication 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.
Lucy S DruryChromosome Replication 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.
Rupert BealeCell Biology of Infection Laboratory, 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
The Francis Crick Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The coronavirus disease 2019 (COVID-19) global pandemic has turned into the largest public health and economic crisis in recent history impacting virtually all sectors of society. There is a need for effective therapeutics to battle the ongoing pandemic. Repurposing existing drugs with known pharmacological safety profiles is a fast and cost-effective approach to identify novel treatments. The COVID-19 etiologic agent is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded positive-sense RNA virus. Coronaviruses rely on the enzymatic activity of the replication-transcription complex (RTC) to multiply inside host cells. The RTC core catalytic component is the RNA-dependent RNA polymerase (RdRp) holoenzyme. The RdRp is one of the key druggable targets for CoVs due to its essential role in viral replication, high degree of sequence and structural conservation and the lack of homologues in human cells. Here, we have expressed, purified and biochemically characterised active SARS-CoV-2 RdRp complexes. We developed a novel fluorescence resonance energy transfer-based strand displacement assay for monitoring SARS-CoV-2 RdRp activity suitable for a high-throughput format. As part of a larger research project to identify inhibitors for all the enzymatic activities encoded by SARS-CoV-2, we used this assay to screen a custom chemical library of over 5000 approved and investigational compounds for novel SARS-CoV-2 RdRp inhibitors. We identified three novel compounds (GSK-650394, C646 and BH3I-1) and confirmed suramin and suramin-like compounds as in vitro SARS-CoV-2 RdRp activity inhibitors. We also characterised the antiviral efficacy of these drugs in cell-based assays that we developed to monitor SARS-CoV-2 growth.

Indexed as

Drug Evaluation, PreclinicalAnimalsAntiviral AgentsBenzoatesBridged Bicyclo Compounds, HeterocyclicChlorocebus aethiopsCoronavirus RNA-Dependent RNA PolymeraseEnzyme AssaysFluorescence Resonance Energy TransferHigh-Throughput Screening AssaysHoloenzymesReproducibility of ResultsSARS-CoV-2Small Molecule LibrariesSuraminVero Cells2-cyclopentyl-4-(5-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl)-benzoic acidAntiviral AgentsBenzoatesBridged Bicyclo Compounds, HeterocyclicCoronavirus RNA-Dependent RNA PolymeraseHoloenzymesNS8 protein, SARS-CoV-2NSP12 protein, SARS-CoV-2ORF1ab polyprotein, SARS-CoV-2Small Molecule LibrariesSuraminViral Nonstructural ProteinscoronavirusCOVID-19nsp12RNA-dependent RNA polymerase

Identifiers

PMID34198323
PMCPMC8286815
OpenAlexW3174137905

What OpenQuestion 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 OpenQuestion graph.