We have previously shown that the acid sphingomyelinase/ceramide system plays an important role in bacterial and viral infections. Pharmacological inhibition of acid sphingomyelinase with amitriptyline, imipramine, fluoxetine, sertraline, escitalopram or maprotiline or genetic down-regulation of the enzyme prevents infection with authentic SARS-CoV-2 or pseudoviral particles expressing pp-VSV-SARS-CoV-2 spike that served as a bona fide system mimicking SARS-CoV-2 infection. Mechanistically, acid sphingomyelinase mediates the formation of ceramide-enriched membrane platforms that serve the infection with pp-VSV-SARS-CoV-2 spike. Neutralization or consumption of surface ceramide reduces infection with pp-VSV-SARS-CoV-2 spike. Treatment of volunteers with a low dose of amitriptyline prevents infection of freshly isolated nasal epithelial cells with pp-VSV-SARS-CoV-2 spike, indicating that amitriptyline can be repurposed to prevent SARS-CoV-2 infection. Our data suggest the use of amitriptyline, a safe drug clinically used for almost 60 years, other antidepressants blocking the acid sphingomyelinase, anti-ceramide antibodies and neutral ceramidase for prophylaxis and treatment of coronavirus disease-19.
Funding: The study was supported by DFG grant Gu-335-35/1 and BMBF, RAPID Consortium, grant 01KI1723D to SP.
Conflict of Interest: The authors declare no competing financial interests.
Ethical Approval: The experiments were approved by the local ethics committee under the number 20-9348-BO.
Carpinteiro, Alexander and Edwards, Michael J. and Hoffmann, Markus and Kochs, Georg and Gripp, Barbara and Weigang, Sebastian and Adams, Constantin and Carpinteiro, Elisa and Gulbins, Anne and Keitsch, Simone and Sehl, Carolin and Soddemann, Matthias and Wilker, Barbara and Kamler, Markus and Bertsch, Thomas and Lang, Karl S. and Patel, Sameer and Wilson, Gregory C. and Walter, Silke and Hengel, Hartmut and Pöhlmann, Stefan and Lang, Philipp and Kornhuber, Johannes and Becker, Katrin Anne and Ahmad, Syed A. and Fassbender, Klaus and Gulbins, Erich, Inhibition of Acid Sphingomyelinase Blocks Infection with SARS-CoV-2. Available at SSRN: https://ssrn.com/abstract=3646562 or http://dx.doi.org/10.2139/ssrn.3646562
This version of the paper has not been formally peer reviewed.
Subscribe to this free journal for more curated articles on this topic
FOLLOWERS
20
PAPERS
9,156
Feedback
Feedback to SSRN
If you need immediate assistance, call 877-SSRNHelp (877 777 6435) in the United States, or +1 212 448 2500 outside of the United States, 8:30AM to 6:00PM U.S. Eastern, Monday - Friday.