{"DOI":"10.1038/s41598-021-85049-0","PMID":"33723270","abstract":"AbstractTo 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\u00a0\u00b5g/ml significantly in these screenings, and the EC50 was determined with 387\u00a0ng/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.","author":[{"family":"Zimniak","given":"Melissa"},{"family":"Kirschner","given":"Luisa"},{"family":"Hilpert","given":"Helen"},{"family":"Geiger","given":"Nina"},{"family":"Danov","given":"Olga"},{"family":"Oberwinkler","given":"Heike"},{"family":"Steinke","given":"Maria"},{"family":"Sewald","given":"Katherina"},{"family":"Seibel","given":"J\u00fcrgen"},{"family":"Bodem","given":"Jochen"}],"id":"unknown","issue":"1","issued":{"date-parts":[[2021,3,15]]},"language":"en","page-first":"5890","publisher":"Springer Science and Business Media LLC","title":"The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue","type":"article-journal","volume":"11"}