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All Studies   Meta Analysis    Recent:   

Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants

Thümmler et al., Viruses, doi:10.3390/v16040545
Mar 2024  
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26th treatment shown to reduce risk in November 2021
 
*, now known with p = 0.00014 from 21 studies, recognized in 3 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19early.org
In Vitro study showing that fluoxetine and sertraline potently neutralize the replication of distinct SARS-CoV-2 variants at subtoxic concentrations. Authors demonstrate that fluoxetine and sertraline inhibit infection with pseudotyped virus-like particles and clinical isolates of SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1, and omicron BA.5 in A549 lung cells overexpressing ACE2 and TMPRSS2. Complete inhibition was achieved at 30μM fluoxetine or 10μM sertraline. The inhibitory effects were validated by RT-qPCR quantification of SARS-CoV-2 M- and N-gene RNA levels. No substantial cytotoxicity was observed at the effective concentrations. As fluvoxamine is a closely related, it may also provide similar inhibition.
3 preclinical studies support the efficacy of fluvoxamine for COVID-19:
Thümmler et al., 30 Mar 2024, peer-reviewed, 21 authors. Contact: adalbert.krawczyk@uk-essen.de (corresponding author), laura.thuemmler@uk-essen.de, peer.brass@uk-essen.de, maren.bormann@uk-essen.de, leonie.brochhagen@uk-essen.de, oliver.witzke@uk-essen.de, monika.lindemann@uk-essen.de, peter.horn@uk-essen.de, carolin.sehl@uk-essen.de, matthias.soddemann@uk-essen.de, stephanie.kadow@uk-essen.de, erich.gulbins@uk-essen.de, katrin.becker-flegler@uni-due.de, carina.elsner@uk-essen.de, ulf.dittmer@uk-essen.de, nicolas.hoertel@aphp.fr, celine.cougoule@ipbs.fr, sandra.ciesek@ukffm.de, marek.widera@ukffm.de, markus.kamler@uk-essen.de.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperFluvoxamineAll
Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants
Laura Thümmler, Nadine Beckmann, Carolin Sehl, Matthias Soddemann, Peer Braß, Maren Bormann, Leonie Brochhagen, Carina Elsner, Nicolas Hoertel, Céline Cougoule, Sandra Ciesek, Marek Widera, Ulf Dittmer, Monika Lindemann, Peter A Horn, Oliver Witzke, Stephanie Kadow, Markus Kamler, Erich Gulbins, Katrin Anne Becker, Adalbert Krawczyk
Viruses, doi:10.3390/v16040545
The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus-like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.
spike protein. This is an interesting finding, as fluoxetine and sertraline were described to interfere with SARS-CoV-2 entry, and at least sertraline directly targeted the SARS-CoV-2 spike protein [7] . In addition to targeting the spike protein, fluoxetine and sertraline were described as functional inhibitors of the acid sphingomyelinase (ASM), which plays an important role during SARS-CoV-2 entry into the host cell [38, 39] . ASM is a glycoprotein that catalyzes sphingomyelin degradation to phosphorylcholine and ceramide, which is known to facilitate viral entry into the host cell [40] [41] [42] . SARS-CoV-2 activates the ASM/ceramide system, resulting in the formation of ceramide-enriched membrane domains that cluster ACE2 and thereby facilitate viral entry and infection [39, 40, 43] . Thus, inhibiting ASM represents a SARS-CoV-2 spike mutation-independent mechanism to interfere with viral entry and infection. In the context of other viral infections, our data indicate that FIASMAs are effective not only against, for example, rhinoviruses [44] or ebolaviruses [45] , but also against SARS-CoV-2. In line with prior studies, our findings suggest that fluoxetine and sertraline use in early-stage SARS-CoV-2 infections with recent variants may reduce the risk of a severe course of COVID-19 or death [46] . However, we have demonstrated the antiviral efficacy of fluoxetine and sertraline against the respective SARS-CoV-2 variants in cell culture. Nonetheless, deriving..
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