Evidence map›Paper›PMID 34575474›Full record

ArticlePharmaceutics2021

Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro.

Linda Brunotte, Shuyu Zheng, Angeles Mecate-Zambrano, Jing Tang, Stephan Ludwig, Ursula Rescher, Sebastian Schloer

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2023
    Pooled it
  2. Extracellular vesicles in viral disease management.Current research in microbial sciences · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
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  11. Evaluation of a series of nucleoside analogs as effective anticoronaviral-2 drugs against the Omicron-B.1.1.529/BA.2 subvariant: A repurposing research study.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2023
    Article
  12. Article
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  14. Article
  15. 3DEmerging microbes & infections · 2022
    Article
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  20. Review
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

7 authors at 2 institutions in 2 countries.

Linda BrunotteInstitute of Virology, Center for Molecular Biology of Inflammation, and "Cells in Motion" Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.
Shuyu ZhengResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, 00029 Helsinki, Finland.
Angeles Mecate-ZambranoInstitute of Virology, Center for Molecular Biology of Inflammation, and "Cells in Motion" Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.
Jing TangResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, 00029 Helsinki, Finland.ORCID 0000-0001-7480-7710
Stephan LudwigInstitute of Virology, Center for Molecular Biology of Inflammation, and "Cells in Motion" Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.ORCID 0000-0003-4490-3052
Ursula RescherInstitut-Associated Research Group Regulatory Mechanisms of Inflammation, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, and "Cells in Motion" Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.ORCID 0000-0001-8892-319X
Sebastian SchloerInstitut-Associated Research Group Regulatory Mechanisms of Inflammation, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, and "Cells in Motion" Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.
Institute of Molecular Biology · DEUniversity of Helsinki · FI

Funding

Academy of Finland No. 317680Bundesministerium für Bildung und Forschung grant number 01KI20218 (CoIMMUNE) and NUM-COVID-19, Organo-Strat 01KX2021 (to L.B. and S.L.)Deutsche Forschungsgemeinschaft CRC1009 "Breaking Barriers", Project A06 (to U.R.) and B02 (to S.L.)Deutsche Forschungsgemeinschaft CRC 1348 "Dynamic Cellular Interfaces", Project A11 (to U.R.)Deutsche Forschungsgemeinschaft KFO342 TP6, Br5189/3-1 (to L.B.), Lu477/30-1 (to S.L.)European Research Council No. 716063Interdisciplinary Center for Clinical Research Univerisity of Muenster Re2/022/20Interdisciplinary Center for Clinical Research University of Muenster Bru2/015/19the Innovative Medizinische Forschung (IMF) of the Münster Medical School SC121912 (to S.S.) and from BR111502 (to L.B.)
6 · The paper itself

Abstract

The ongoing SARS-CoV-2 pandemic requires efficient and safe antiviral treatment strategies. Drug repurposing represents a fast and low-cost approach to the development of new medical treatment options. The direct antiviral agent remdesivir has been reported to exert antiviral activity against SARS-CoV-2. Whereas remdesivir only has a very short half-life time and a bioactivation, which relies on pro-drug activating enzymes, its plasma metabolite GS-441524 can be activated through various kinases including the adenosine kinase (ADK) that is moderately expressed in all tissues. The pharmacokinetics of GS-441524 argue for a suitable antiviral drug that can be given to patients with COVID-19. Here, we analyzed the antiviral property of a combined treatment with the remdesivir metabolite GS-441524 and the antidepressant fluoxetine in a polarized Calu-3 cell culture model against SARS-CoV-2. The combined treatment with GS-441524 and fluoxetine were well-tolerated and displayed synergistic antiviral effects against three circulating SARS-CoV-2 variants in vitro in the commonly used reference models for drug interaction. Thus, combinatory treatment with the virus-targeting GS-441524 and the host-directed drug fluoxetine might offer a suitable therapeutic treatment option for SARS-CoV-2 infections.

Indexed as

combination therapyfluoxetinenucleoside GS-441524SARS-CoV-2synergy

Identifiers

PMID34575474
PMCPMC8466181
OpenAlexW3198788991

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.