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. 2021 Apr 20:12:652688.
doi: 10.3389/fphar.2021.652688. eCollection 2021.

Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19

Vikas P Sukhatme  1 , Angela M Reiersen  2 , Sharat J Vayttaden  3 , Vidula V Sukhatme  4   5
Affiliations

Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19

Vikas P Sukhatme et al. Front Pharmacol. .

Abstract

Fluvoxamine is a well-tolerated, widely available, inexpensive selective serotonin reuptake inhibitor that has been shown in a small, double-blind, placebo-controlled, randomized study to prevent clinical deterioration of patients with mild coronavirus disease 2019 (COVID-19). Fluvoxamine is also an agonist for the sigma-1 receptor, through which it controls inflammation. We review here a body of literature that shows important mechanisms of action of fluvoxamine and other SSRIs that could play a role in COVID-19 treatment. These effects include: reduction in platelet aggregation, decreased mast cell degranulation, interference with endolysosomal viral trafficking, regulation of inositol-requiring enzyme 1α-driven inflammation and increased melatonin levels, which collectively have a direct antiviral effect, regulate coagulopathy or mitigate cytokine storm, which are known hallmarks of severe COVID-19.

Keywords: SARS-CoV-2; acute respiratory distress syndrome; cytokine storm; inflammation; interleukins.

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Conflict of interest statement

Author VVS was employed by the company GlobalCures, Inc. Author AR has received research support for clinical trials of fluvoxamine for COVID-19 from the Taylor Family Institute for Innovative Psychiatric Treatment at Washington University, Fast Grants, and the COVID-19 Early Treatment Fund, and she is an inventor on a patent application filed by Washington University in St. Louis, which is relevant to methods of treating COVID-19, including fluvoxamine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Potential anti-COVID-19 mechanisms of action of fluvoxamine. Figure created using Biorender.
See this image and copyright information in PMC

References

    1. Ackermann M., Verleden S. E., Kuehnel M., Haverich A., Welte T., Laenger F., et al. (2020). Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid-19. N. Engl. J. Med. 383 (2), 120–128. 10.1056/nejmoa2015432 - DOI - PMC - PubMed
    1. Alidjinou E. K., Bertin A., Sane F., Caloone D., Engelmann I., Hober D. (2019). Emergence of fluoxetine-resistant variants during treatment of human pancreatic cell cultures persistently infected with coxsackievirus B4. Viruses 11 (6), 486. 10.3390/v11060486 - DOI - PMC - PubMed
    1. Althaus K., Marini I., Zlamal J., Pelzl L., Singh A., Häberle H., et al. (2020). Antibody-induced procoagulant platelets in severe COVID-19 infection. Blood 137 (8), 1061–1071. 10.1182/blood.2020008762 - DOI - PMC - PubMed
    1. Armocida D., Palmieri M., Frati A., Santoro A., Pesce A. (2020). How SARS-Cov-2 can involve the central nervous system. A systematic analysis of literature of the department of human neurosciences of Sapienza University, Italy. J. Clin. Neurosci. 79, 231–236. 10.1016/j.jocn.2020.07.007 - DOI - PMC - PubMed
    1. Baharav E., Bar M., Taler M., Gil-Ad I., Karp L., Weinberger A., et al. (2012). Immunomodulatory effect of sertraline in a rat model of rheumatoid arthritis. Neuroimmunomodulation 19 (5), 309–318. 10.1159/000339109 - DOI - PubMed

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