Evidence map›Paper›PMID 36644320›Full record

ArticleiScience2023

Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform.

Denisa Bojkova, Philipp Reus, Leona Panosch, Marco Bechtel, Tamara Rothenburger, Joshua D Kandler, Annika Pfeiffer, Julian U G Wagner, Mariana Shumliakivska, Stefanie Dimmeler and 15 more

Abstract read
In one paragraph

Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. CMGC Kinases in Viral Infection and Human Disease.Pathogens (Basel, Switzerland) · 2026
    Review
  2. Article
  3. Article
  4. EfficientAntimicrobial agents and chemotherapy · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. 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

25 authors.

Denisa BojkovaInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Philipp ReusInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Leona PanoschInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Marco BechtelInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Tamara RothenburgerInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Joshua D KandlerInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Annika PfeifferInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Julian U G WagnerInstitute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
Mariana ShumliakivskaInstitute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
Stefanie DimmelerInstitute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
Ruth OlmerLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Ulrich MartinLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Florian W R VondranDepartment for General, Visceral and Transplant Surgery, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Tuna ToptanInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Florian RothweilerInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Richard ZehnerInstitute for Forensic Medicine, University Hospital, Goethe-University, Kennedyallee 104, 60596 Frankfurt am Main, Germany.
Holger F RabenauInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Karen L OsmanUK Health Safety Agency, National Infection Service, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
Steven T PullanUK Health Safety Agency, National Infection Service, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
Miles W CarrollWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, Oxford University, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
Richard StackSchool of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
Sandra CiesekInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
Mark N WassSchool of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
Martin MichaelisSchool of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
Jindrich CinatlInstitute of Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a readout for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in numerous cell culture models, independently of cytopathogenic effect formation. Compared to other models, the Caco-2 subline Caco-2-F03 displayed superior performance. It possesses a stable SARS-CoV-2 susceptibility phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1,796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of phosphoglycerate dehydrogenase (PHGDH), CDC like kinase 1 (CLK-1), and colony stimulating factor 1 receptor (CSF1R). The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the hexokinase II (HK2) inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2-F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false-positive hits.

Indexed as

DrugsScreening in health technologyVirology

Identifiers

PMID36644320
PMCPMC9822553

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.