ArticleCells2022
The Acid Ceramidase Is a SARS-CoV-2 Host Factor.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- The K247 ubiquitination site of the Newcastle disease virus M protein enhances viral budding to facilitate rapid exploitation of host cell sphingolipid metabolites.Poultry science · 2026Article
- Plasma Ceramides Levels in Severe COVID-19 Disease: Correlations with Survival.Open forum infectious diseases · 2026Article
- Article
- Acid ceramidase regulates CD8+ T-cell exhaustion via type I interferon-mediated upregulation of PD-L1.Frontiers in immunology · 2025Article
- Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants.Viruses · 2024Article
- Ceramide promotes lytic reactivation of Epstein-Barr virus in gastric carcinoma.Journal of virology · 2024Article
- Lipid Metabolism Modulation during SARS-CoV-2 Infection: A Spotlight on Extracellular Vesicles and Therapeutic Prospects.International journal of molecular sciences · 2024Review
- The Sphingolipid-Signaling Pathway as a Modulator of Infection by SARS-CoV-2.Current issues in molecular biology · 2023Review
- Azido-Ceramides, a Tool to Analyse SARS-CoV-2 Replication and Inhibition-SARS-CoV-2 Is Inhibited by Ceramides.International journal of molecular sciences · 2023Article
- Cell Type-Specific Anti-Viral Effects of Novel SARS-CoV-2 Main Protease Inhibitors.International journal of molecular sciences · 2023Article
- Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 - inhibition of SARS-CoV-2 is cell line-specific.Frontiers in cellular and infection microbiology · 2023Article
- Lipid compartments and lipid metabolism as therapeutic targets against coronavirus.Frontiers in immunology · 2023Review
- Causal associations between major depressive disorder and COVID-19.General psychiatry · 2023Article
- Acetylsalicylic Acid and Salicylic Acid Inhibit SARS-CoV-2 Replication in Precision-Cut Lung Slices.Vaccines · 2022Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2 variants such as the delta or omicron variants, with higher transmission rates, accelerated the global COVID-19 pandemic. Thus, novel therapeutic strategies need to be deployed. The inhibition of acid sphingomyelinase (ASM), interfering with viral entry by fluoxetine was reported. Here, we described the acid ceramidase as an additional target of fluoxetine. To discover these effects, we synthesized an ASM-independent fluoxetine derivative, AKS466. High-resolution SARS-CoV-2-RNA FISH and RTqPCR analyses demonstrate that AKS466 down-regulates viral gene expression. It is shown that SARS-CoV-2 deacidifies the lysosomal pH using the ORF3 protein. However, treatment with AKS488 or fluoxetine lowers the lysosomal pH. Our biochemical results show that AKS466 localizes to the endo-lysosomal replication compartments of infected cells, and demonstrate the enrichment of the viral genomic, minus-stranded RNA and mRNAs there. Both fluoxetine and AKS466 inhibit the acid ceramidase activity, cause endo-lysosomal ceramide elevation, and interfere with viral replication. Furthermore, Ceranib-2, a specific acid ceramidase inhibitor, reduces SARS-CoV-2 replication and, most importantly, the exogenous supplementation of C6-ceramide interferes with viral replication. These results support the hypotheses that the acid ceramidase is a SARS-CoV-2 host factor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.