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

被引:133
作者
Sukhatme, Vikas P. [1 ,2 ]
Reiersen, Angela M. [3 ]
Vayttaden, Sharat J.
Sukhatme, Vidula V. [4 ,5 ]
机构
[1] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA
[2] Emory Univ, Morningside Ctr Innovat & Affordable Med, Sch Med, Atlanta, GA USA
[3] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA
[4] GlobalCures Inc, Newton, MA USA
[5] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA
关键词
SARS-CoV-2; cytokine storm; acute respiratory distress syndrome; interleukins; inflammation; SEROTONIN REUPTAKE INHIBITORS; ENDOPLASMIC-RETICULUM STRESS; PLATELET SEROTONIN; MAST-CELLS; FUNCTIONAL INHIBITORS; THERAPEUTIC TARGET; SIGMA-RECEPTORS; RAT MODEL; VIRUS; ACTIVATION;
D O I
10.3389/fphar.2021.652688
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 1 alpha-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.
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页数:9
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共 113 条
[1]   Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19 [J].
Ackermann, Maximilian ;
Verleden, Stijn E. ;
Kuehnel, Mark ;
Haverich, Axel ;
Welte, Tobias ;
Laenger, Florian ;
Vanstapel, Arno ;
Werlein, Christopher ;
Stark, Helge ;
Tzankov, Alexandar ;
Li, William W. ;
Li, Vincent W. ;
Mentzer, Steven J. ;
Jonigk, Danny .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (02) :120-128
[2]   Emergence of Fluoxetine-Resistant Variants during Treatment of Human Pancreatic Cell Cultures Persistently Infected with Coxsackievirus B4 [J].
Alidjinou, Enagnon Kazali ;
Bertin, Antoine ;
Sane, Famara ;
Caloone, Delphine ;
Engelmann, Ilka ;
Hober, Didier .
VIRUSES-BASEL, 2019, 11 (06)
[3]   Antibody-induced procoagulant platelets in severe COVID-19 infection [J].
Althaus, Karina ;
Marini, Irene ;
Zlamal, Jan ;
Pelzl, Lisann ;
Singh, Anurag ;
Haberle, Helene ;
Mehrlander, Martin ;
Hammer, Stefanie ;
Schulze, Harald ;
Bitzer, Michael ;
Malek, Nisar ;
Rath, Dominik ;
Bosmuller, Hans ;
Nieswandt, Bernard ;
Gawaz, Meinrad ;
Bakchoul, Tamam ;
Rosenberger, Peter .
BLOOD, 2021, 137 (08) :1061-1071
[4]   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].
Armocida, Daniele ;
Palmieri, Mauro ;
Frati, Alessandro ;
Santoro, Antonio ;
Pesce, Alessandro .
JOURNAL OF CLINICAL NEUROSCIENCE, 2020, 79 :231-236
[5]   Immunomodulatory Effect of Sertraline in a Rat Model of Rheumatoid Arthritis [J].
Baharav, Ehud ;
Bar, Meytal ;
Taler, Michal ;
Gil-Ad, Irit ;
Karp, Leon ;
Weinberger, Abraham ;
Weizman, Avraham .
NEUROIMMUNOMODULATION, 2012, 19 (05) :309-318
[6]   Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis, Treatment, and Prevention [J].
Bale, James F., Jr. .
PEDIATRIC NEUROLOGY, 2015, 53 (01) :3-12
[7]   Fluoxetine Inhibits Enterovirus Replication by Targeting the Viral 2C Protein in a Stereospecific Manner [J].
Bauer, Lisa ;
Manganaro, Roberto ;
Zonsics, Birgit ;
Strating, Jeroen R. P. M. ;
El Kazzi, Priscila ;
Lopez, Moira Lorenzo ;
Ulferts, Rachel ;
van Hoey, Clara ;
Mate, Maria J. ;
Langer, Thierry ;
Coutard, Bruno ;
Brancale, Andrea ;
van Kuppeveld, Frank J. M. .
ACS INFECTIOUS DISEASES, 2019, 5 (09) :1609-1623
[8]   The Expanded Biology of Serotonin [J].
Berger, Miles ;
Gray, John A. ;
Roth, Bryan L. .
ANNUAL REVIEW OF MEDICINE, 2009, 60 :355-366
[9]   Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response [J].
Bernales, Sebastian ;
McDonald, Kent L. ;
Walter, Peter .
PLOS BIOLOGY, 2006, 4 (12) :2311-2324
[10]   Emerging mechanisms of drug-induced phospholipidosis [J].
Breiden, Bernadette ;
Sandhoff, Konrad .
BIOLOGICAL CHEMISTRY, 2020, 401 (01) :31-46