Tury. A total of 92,977,768 confirmed cases of COVID-19 and 1,991,289 deaths were reported globally up to January 14, 2021. COVID-19 also affects people’s mental well being and high-quality of life. At present, there is no productive therapeutic method for the management of this illness. Thus, in the absence of a particular vaccine or curative remedy, it truly is an urgent will need to identify safe, powerful and globally offered drugs for decreasing COVID-19 morbidity and fatalities. Within this overview, we concentrate on selective serotonin reuptake inhibitors (SSRIs: a class of antidepressant drugs with widespread MMP-13 list availability and an optimal tolerability profile) which will potentially be repurposed for COVID-19 and are presently becoming tested in clinical trials. We also summarize the PKCĪµ medchemexpress current literature on what’s recognized about the link in between serotonin (5-HT) plus the immune system. From the evidence reviewed here, we propose fluoxetine as an adjuvant therapeutic agent for COVID-19 primarily based on its recognized immunomodulatory, anti-inflammatory and antiviral properties. Fluoxetine may perhaps potentially reduce proinflammatory chemokine/cytokines levels (such as CCL-2, IL-6, and TNF-a) in COVID-19 sufferers. Moreover, fluoxetine could enable to attenuate neurological complications of COVID-19. 2021 Elsevier Ltd. All rights reserved.Post history: Received 14 January 2021 Accepted 11 MarchKeywords: COVID-19 SARS-CoV-2 Drug repurposing Antidepressant drugs Selective serotonin reuptake inhibitors (SSRIs) Anti-inflammatory1. Introduction The novel coronavirus disease 2019 (COVID-19), a systemic infection potentially targeting many organs and functions, is at present leading to a international pandemic. The mortality rate of COVID-19 appears to become inside the array of three.four.five , which can be considerably larger than that for seasonal flu caused by the influenza virus (1 ) [1]. In the time of writing the write-up (14 January 2021), humanity is struggling together with the serious acute respiratoryAbbreviations: ACE-2, Angiotensin converting enzyme II; ARDS, Acute respiratory distress syndrome; ALI, Acute lung injury; APOE e4, Apolipoprotein E4; AUC, Location below the curve; Cmax, Maximum plasma concentration; COVID-2019, Coronavirus illness 2019; CS, Cytokine storm; CLpro, Chemotrypsin-like protease; CYP, Cytochrome P450; CV-B3, Coxsackievirus B3; CCR5, C-C chemokine receptor form five; DENV, Dengue virus; EV, Enteroviruses; EBOV, Ebola virus; 5-HT, 5Hydroxytryptamine; HCV, Hepatitis C virus; HIV, Human immunodeficiency virus; IL-1b, Interleukin-1beta; IFN-c, Interferon-gamma; NK, Natural Killer; NF-jB, Nuclear aspect kappa B; PK, Pharmacokinetic; PD, Pharmacodynamic; Panc-1, Pancreatic cells; PLpro, Papain-like protease; RdRp, RNA-dependent RNA polymerase; SERT, Serotonin reuptake transporter; S1R, Sigma-1 receptor; SSRIs, Selective serotonin reuptake inhibitors; SARS-CoV-2, Serious acute respiratory syndrome coronavirus two; SS, Serotonin syndrome; TNF-a, Tumor necrosis factoralpha; TGF-b1, Transforming development factor beta 1; VD, Volume of distribution. E-mail address: [email protected] https://doi.org/10.1016/j.jocn.2021.03.010 0967-5868/2021 Elsevier Ltd. All rights reserved.syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, which has already infected greater than 90.9 million people today and brought on more than 1.9 million deaths worldwide [2]. This rapid and unprecedented pandemic has caused serious psychological troubles, for example anxiousness (panic attacks and post-traumatic anxiety) and depression [3]. St.