TY  - JOUR
A1  - Zimniak, Melissa
A1  - Kirschner, Luisa
A1  - Hilpert, Helen
A1  - Geiger, Nina
A1  - Danov, Olga
A1  - Oberwinkler, Heike
A1  - Steinke, Maria
A1  - Sewald, Katherina
A1  - Seibel, Jürgen
A1  - Bodem, Jochen
T1  - The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue
JF  - Scientific Reports
N2  - 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 mu g/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.
KW  - SARS-CoV-2
KW  - viral epidemiology
KW  - viral infection
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259820
VL  - 11
ER  - 
TY  - JOUR
A1  - Batool, Farwa
A1  - Saeed, Muhammad
A1  - Saleem, Hafiza Nosheen
A1  - Kirschner, Luisa
A1  - Bodem, Jochen
T1  - Facile synthesis and in vitro activity of N-substituted 1,2-benzisothiazol-3(2H)-ones against dengue virus NS2BNS3 protease
JF  - Pathogens
N2  - Several new N-substituted 1,2-benzisothiazol-3(2H)-ones (BITs) were synthesised through a facile synthetic route for testing their anti-dengue protease inhibition. Contrary to the conventional multistep synthesis, we achieved structurally diverse BITs with excellent yields using a two-step, one-pot reaction strategy. All the synthesised compounds were prescreened for drug-like properties using the online Swiss Absorption, Distribution, Metabolism and Elimination (SwissADME) model, indicating their favourable pharmaceutical properties. Thus, the synthesised BITs were tested for inhibitory activity against the recombinant dengue virus serotype-2 (DENV-2) NS2BNS3 protease. Dose–response experiments and computational docking analyses revealed that several BITs bind to the protease in the vicinity of the catalytic triad with IC\(_{50}\) values in the micromolar range. The DENV2 infection assay showed that two BITs, 2-(2-chlorophenyl)benzo[d]isothiazol-3(2H)-one and 2-(2,6-dichlorophenyl)benzo[d]isothiazol-3(2H)-one, could suppress DENV replication and virus infectivity. These results indicate the potential of BITs for developing new anti-dengue therapeutics.
KW  - dengue virus
KW  - direct-acting antivirals
KW  - 1,2-benzisothiazolinone
KW  - drug discovery
KW  - infectivity assays
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236605
SN  - 2076-0817
VL  - 10
IS  - 4
ER  -