The Acid Ceramidase Is a SARS-CoV-2 Host Factor

Geiger, Nina; Kersting, Louise; Schlegel, Jan; Stelz, Linda; Fähr, Sofie; Diesendorf, Viktoria; Roll, Valeria; Sostmann, Marie; König, Eva-Maria; Reinhard, Sebastian; Brenner, Daniela; Schneider‐Schaulies, Sibylle; Sauer, Markus; Seibel, Jürgen; Bodem, Jochen

doi:10.3390/cells11162532

Cited by 15 publications

(21 citation statements)

References 39 publications

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“…A previously described, patient-derived, and completely sequenced SARS-CoV-2 isolate was used for infection experiments [ 5 , 8 , 16 ]. Vero, Huh-7, and A549-ACE2 cells were cultured in DMEM medium (Life Technologies, Darmstadt, Germany) supplemented with 10% foetal calf serum (Merck-Sigma Aldrich, Taufkirchen, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Acetylsalicylic Acid and Salicylic Acid Inhibit SARS-CoV-2 Replication in Precision-Cut Lung Slices

et al. 2022

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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.

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Section: Methodsmentioning

confidence: 99%

“…However, compounds analysed on human PCLS, such as fluoxetine, were beneficial in clinical studies. Moreover, the analyses of the antiviral mechanisms of these compounds led to the identification of new side activities of these drugs, such as the inhibition of the acidic ceramidase by fluoxetine [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Acetylsalicylic Acid and Salicylic Acid Inhibit SARS-CoV-2 Replication in Precision-Cut Lung Slices

et al. 2022

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“…Vero and Huh-7 cells were incubated with the compounds, and the cell growth rate was compared to untreated cells. In addition, we performed viability assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) on these cell lines and Calu-3 cells, as described previously [ 14 , 15 , 16 , 17 ]. Concentrations reducing cell growth or catabolism by 15% or more were excluded from further analyses ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Cell Type-Specific Anti-Viral Effects of Novel SARS-CoV-2 Main Protease Inhibitors

Geiger

Diesendorf

Roll

et al. 2023

IJMS

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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.

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“…Recently we have shown that inhibition of the ceramidase raised ceramide concentration and inhibited SARS-CoV-2 replication, similar to treatment with short-chain C6-ceramide [ 29 ]. However, the subcellular location of the C6-ceramide in SARS-CoV-2 permissive cells was not determined.…”

Section: Resultsmentioning

confidence: 99%

Azido-Ceramides, a Tool to Analyse SARS-CoV-2 Replication and Inhibition—SARS-CoV-2 Is Inhibited by Ceramides

Brenner

Geiger

Schlegel

et al. 2023

IJMS

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Recently, we have shown that C6-ceramides efficiently suppress viral replication by trapping the virus in lysosomes. Here, we use antiviral assays to evaluate a synthetic ceramide derivative α-NH2-ω-N3-C6-ceramide (AKS461) and to confirm the biological activity of C6-ceramides inhibiting SARS-CoV-2. Click-labeling with a fluorophore demonstrated that AKS461 accumulates in lysosomes. Previously, it has been shown that suppression of SARS-CoV-2 replication can be cell-type specific. Thus, AKS461 inhibited SARS-CoV-2 replication in Huh-7, Vero, and Calu-3 cells up to 2.5 orders of magnitude. The results were confirmed by CoronaFISH, indicating that AKS461 acts comparable to the unmodified C6-ceramide. Thus, AKS461 serves as a tool to study ceramide-associated cellular and viral pathways, such as SARS-CoV-2 infections, and it helped to identify lysosomes as the central organelle of C6-ceramides to inhibit viral replication.

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The Acid Ceramidase Is a SARS-CoV-2 Host Factor

Cited by 15 publications

References 39 publications

Acetylsalicylic Acid and Salicylic Acid Inhibit SARS-CoV-2 Replication in Precision-Cut Lung Slices

Acetylsalicylic Acid and Salicylic Acid Inhibit SARS-CoV-2 Replication in Precision-Cut Lung Slices

Cell Type-Specific Anti-Viral Effects of Novel SARS-CoV-2 Main Protease Inhibitors

Azido-Ceramides, a Tool to Analyse SARS-CoV-2 Replication and Inhibition—SARS-CoV-2 Is Inhibited by Ceramides

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