Repurposing antidepressants inhibiting the sphingomyelinase acid/ceramide system against COVID-19: current evidence and potential mechanisms
Nicolas Hoertel, Marina Sánchez-Rico, Céline Cougoule, Erich Gulbins, Johannes Kornhuber, Alexander Carpinteiro, Katrin Anne Becker, Angela M Reiersen, Eric J Lenze, David Seftel, Cédric Lemogne, Frédéric Limosin
Molecular Psychiatry, doi:10.1038/s41380-021-01254-3
Molecular Psychiatry might collectively lead to anti-SARS-COV-2 effects while diminishing coagulopathy and cytokine storm consequences, which are known hallmarks of severe COVID-19. Following these preclinical, observational and clinical converging findings, and as stated by Salles et al. [1] and Stip et al. [2], large-scale double-blind placebo-controlled randomized clinical trials of FIASMA antidepressants for COVID-19 at different stages of the disease, either alone or combined with medications that have shown preliminary evidence of potential efficacy and good tolerability, are urgently needed. Fluoxetine and fluvoxamine, which display high in vitro inhibition effect on ASM, showed potential positive effects at usual antidepressant doses, and are easy to use, including high safety margins, good tolerability, widespread availability and low cost, should be considered compelling treatments to prioritize for phase 3 trials against .
AUTHOR CONTRIBUTIONS Writing-original draft: NH; Writing-review & editing: MS-R, CG, EG, JK, AC, KAB, AMR, EJL, DS, CL, FL.
COMPETING INTERESTS
ADDITIONAL INFORMATION Correspondence and requests for materials should be addressed to N.H. Reprints and permission information is available at http://www.nature.com/ reprints Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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{ 'value': 'NH, MS-R, EG, JK, AC, and FL are inventors on a patent application related to '
'methods of treating COVID-19, filled by Assistance Publique —Hopitaux de Paris '
'in France. NH has received personal fees and nonfinancial support from '
'Lundbeck, outside the submitted work. AMR and EJL are inventors on a patent '
'application related to methods of treating COVID-19, which was filed by '
'Washington University in St. Louis. EJL has received consulting fees from '
'Johnson and Johnson, and Jazz Pharmaceuticals. AMR has received grant or '
'research support from the McDonnell Center for Systems Neuroscience, the '
'McDonnell Center for Cellular and Molecular Neurobiology, and the Taylor Family '
'Institute for Innovative Psychiatric Research. DS is the Chief Medical Officer '
'and CEO of Enable Biosciences, a CLIA certified Federal clinical reference '
'laboratory that performs COVID-19 antibody testing. CL reports personal fees '
'and nonfinancial support from Janssen-Cilag, Lundbeck, Otsuka Pharmaceutical, '
'and Boehringer Ingelheim, outside the submitted work. FL has received speaker '
'and consulting fees from Janssen-Cilag, Euthérapie-Servier, and Lundbeck, '
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