The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2
Open accessPreprint — published as 10.1038/s41598-021-85049-0
Abstract
To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications “off-label” against SARS-CoV-2. In these screenings, Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8µg/ml significantly, and the EC50 was determined with 387ng/ml. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus. Fluoxetine treatment resulted in a decrease in viral protein expression. Furthermore, Fluoxetine inhibited neither Rabies virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex virus type 1 gene expression, indicating that it acts virus-specific. We see the role of Fluoxetine in the early treatment of SARS-CoV-2 infected patients of risk groups.
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The SSRI fluoxetine may have in-vitro antiviral effects on SARS-CoV-2, although this effect was not observed for paroxetine and escitalopram.
“A recent in-vitro study [12] also supports antiviral effects of the SSRI fluoxetine on SARS-CoV-2, although this effect was not observed for other SSRIs, including paroxetine and escitalopram.”
From Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study (2021) · cites this paper as [12]
Certain antidepressants, such as fluoxetine, may have antiviral effects on SARS-CoV-2.
“Finally, certain antidepressants may exert antiviral effects on SARS-CoV-2, such as fluoxetine [12].”
From Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study (2021) · cites this paper as [12]
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“Preclinical evidence has also demonstrated the in vitro efficacy of several SSRIs against various variants of SARS-CoV-2, both in human and nonhuman host cells [9].”
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“The inclusion criteria consisted of (1) age of 16 to 65 years old, (2) dominant to the Persian language, (3) hospitalized patients with COVID19 infection with positive PCR results or typical lung CT scan findings, (4) no history of MDD and other acute psychiatric disorders and no consumption of psychotropic drugs duri…”
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“The assumed mechanism consists of inhibition of acid sphingomyelinase activity [149], prevention of epithelial cell infection [150], controlling cytokine storm via acting as S1R agonist [151,152], lowering inflammatory mediators [145,146], and some antiviral effects [153].”
BackgroundSSRIs and SNRIs and Risk of Death or Intubation in COVID-19: Results from an Observational StudyPreprint
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Diversity of mechanism of action of psychotropic drugs in their anti-COVID-19 properties
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Repurposing Selective Serotonin Reuptake Inhibitors for COVID-19: Rationale and Concerns
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Prescription of selective serotonin reuptake inhibitors in COVID-19 infection needs caution
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“Tests for homogeneity: overall, Q(4) = 18.”
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A Multi-Dimensional Psychiatric Perspective on the Impact of the COVID-19 Pandemic
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- Authors
- Zimniak, M., Kirschner, L., Hilpert, H., Seibel, J., & Bodem, J.
- Affiliations
- University of Würzburg (DE)
- Corresponding author
- Bodem, Jochen
- Venue
- Scientific Reports
- Publisher
- openRxiv
- Published
- 2020-06-14
- Volume
- 11
- Issue
- 1
- Pages
- 5890-5890
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7961020
- OpenAlex
- W3135929914
- Cited by
- 139
- References
- 6
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 13 · 2023: 22 · 2022: 38 · 2021: 45 · 2020: 8
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion, other-oa)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Funders
- Julius-Maximilians-Universität Würzburg
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- fluoxetine, SARS-CoV-2, COVID-19 pandemic, antiviral drug repurposing, precision-cut lung slices, viral replication inhibition, stereoisomers, cytokine inhibition, viral gene expression
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Animals, Antiviral Agents, Cell Line, Cells, Cultured, Fluoxetine, Humans, Lung, Virus Replication, Selective Serotonin Reuptake Inhibitors
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