The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue

• Published in: Scientific reports Vol. 11; no. 1; pp. 5890 - 5
• Main Authors: Zimniak, Melissa, Kirschner, Luisa, Hilpert, Helen, Geiger, Nina, Danov, Olga, Oberwinkler, Heike, Steinke, Maria, Sewald, Katherina, Seibel, Jürgen, Bodem, Jochen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/596/2562; 631/326/596/4130; 692/699/255/2514; Animals; Antidepressants; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Cell Line; Cells, Cultured; Clinical trials; COVID-19; COVID-19 - drug therapy; COVID-19 - virology; Cytokines; Fluoxetine; Fluoxetine - pharmacology; Fluoxetine - therapeutic use; Gene expression; Herpes simplex; Humanities and Social Sciences; Humans; Infectivity; Isomers; Lung - drug effects; Lung - pathology; Lung - virology; Lyssavirus; multidisciplinary; Rabies; Respiratory syncytial virus; Risk groups; SARS-CoV-2 - drug effects; Science; Science (multidisciplinary); Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - pharmacology; Serotonin Uptake Inhibitors - therapeutic use; Severe acute respiratory syndrome coronavirus 2; Stereoisomers; Virus Replication - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-85049-0

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. Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8 µg/ml significantly in these screenings, and the EC50 was determined with 387 ng/ml. Furthermore, Fluoxetine reduced viral infectivity in precision-cut human lung slices showing its activity in relevant human tissue targeted in severe infections. Fluoxetine treatment resulted in a decrease in viral protein expression. 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, indicating that the R-form might specifically be used for SARS-CoV-2 treatment. 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. Moreover, since it is known that Fluoxetine inhibits cytokine release, we see the role of Fluoxetine in the treatment of SARS-CoV-2 infected patients of risk groups.