PT - JOURNAL ARTICLE AU - Zimniak, Melissa AU - Kirschner, Luisa AU - Hilpert, Helen AU - Seibel, Jürgen AU - Bodem, Jochen TI - The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 AID - 10.1101/2020.06.14.150490 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.06.14.150490 4099 - http://biorxiv.org/content/early/2020/06/17/2020.06.14.150490.short 4100 - http://biorxiv.org/content/early/2020/06/17/2020.06.14.150490.full AB - 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.Competing Interest StatementThe authors have declared no competing interest.