TY  - JOUR
A1  - Geiger, Nina
A1  - König, Eva-Maria
A1  - Oberwinkler, Heike
A1  - Roll, Valeria
A1  - Diesendorf, Viktoria
A1  - Fähr, Sofie
A1  - Obernolte, Helena
A1  - Sewald, Katherina
A1  - Wronski, Sabine
A1  - Steinke, Maria
A1  - Bodem, Jochen
T1  - Acetylsalicylic acid and salicylic acid inhibit SARS-CoV-2 replication in precision-cut lung slices
JF  - Vaccines
N2  - Aspirin, with its active compound acetylsalicylic acid (ASA), shows antiviral activity against rhino- and influenza viruses at high concentrations. We sought to investigate whether ASA and its metabolite salicylic acid (SA) inhibit SARS-CoV-2 since it might use similar pathways to influenza viruses. The compound-treated cells were infected with SARS-CoV-2. Viral replication was analysed by RTqPCR. The compounds suppressed SARS-CoV-2 replication in cell culture cells and a patient-near replication system using human precision-cut lung slices by two orders of magnitude. While the compounds did not interfere with viral entry, it led to lower viral RNA expression after 24 h, indicating that post-entry pathways were inhibited by the compounds.
KW  - acetylsalicylic acid
KW  - salicylic acid
KW  - antiviral activity
KW  - aspirin
KW  - SARS-CoV-2
KW  - precision-cut lung slices
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-289885
SN  - 2076-393X
VL  - 10
IS  - 10
ER  - 
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  - Geiger, Nina
A1  - Diesendorf, Viktoria
A1  - Roll, Valeria
A1  - König, Eva-Maria
A1  - Obernolte, Helena
A1  - Sewald, Katherina
A1  - Breidenbach, Julian
A1  - Pillaiyar, Thanigaimalai
A1  - Gütschow, Michael
A1  - Müller, Christa E.
A1  - Bodem, Jochen
T1  - Cell type-specific anti-viral effects of novel SARS-CoV-2 main protease inhibitors
JF  - International Journal of Molecular Sciences
N2  - Recently, we have described novel pyridyl indole esters and peptidomimetics as potent inhibitors of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) main protease. Here, we analysed the impact of these compounds on viral replication. It has been shown that some antivirals against SARS-CoV-2 act in a cell line-specific way. Thus, the compounds were tested in Vero, Huh-7, and Calu-3 cells. We showed that the protease inhibitors at 30 µM suppress viral replication by up to 5 orders of magnitude in Huh-7 cells, while in Calu-3 cells, suppression by 2 orders of magnitude was achieved. Three pyridin-3-yl indole-carboxylates inhibited viral replication in all cell lines, indicating that they might repress viral replication in human tissue as well. Thus, we investigated three compounds in human precision-cut lung slices and observed donor-dependent antiviral activity in this patient-near system. Our results provide evidence that even direct-acting antivirals may act in a cell line-specific manner.
KW  - SARS-CoV-2
KW  - protease inhibitors
KW  - cell line specificity pyridyl indole carboxylates
KW  - azapeptide nitriles
KW  - peptidomimetics
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304034
SN  - 1422-0067
VL  - 24
IS  - 4
ER  -