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Repurposing antidepressants inhibiting the sphingomyelinase acid/ceramide system against COVID-19: current evidence and potential mechanisms

Hoertel et al., Molecular Psychiatry, doi:10.1038/s41380-021-01254-3
Aug 2021  
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Review of the mechanisms of action and clinical studies for the treatment of COVID-19 with FIASMA antidepressants such as fluoxetine, fluvoxamine, paroxetine, escitalopram, or amitriptyline.
Hoertel et al., 12 Aug 2021, peer-reviewed, 12 authors.
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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 reprints Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Schloer, Brunotte, Goretzko, Mecate-Zambrano, Korthals et al., Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine, Emerg Microbes Infect
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