The association between obesity and poor outcome after COVID-19 indicates a potential therapeutic role for montelukast

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved..

It is widely believed that infection with the SARS-CoV-2 virus triggers a disproportionate immune response which causes a devastating systemic injury, particularly in individuals with obesity, itself a chronic, multi-organ inflammatory disease. Immune cells accumulate in visceral adipose tissue and together with paracrine adipocytes release a wide range of biologically active cytokines (including IL-1β, IL5, IL6 and IL8) that can result in both local, pulmonary and systemic inflammation. A more intense 'cytokine storm' is postulated as the mechanism behind the extreme immune response seen in severe COVID-19. It is striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality. Furthermore, patients from a BAME background appear to have increased mortality after SARS-CoV-2 infection; they also have a higher prevalence of central obesity and its metabolic complications. In the absence of an effective vaccine, the therapeutic potential of immune-modulating drugs is a priority, but the development of new drugs is expensive and time-consuming. A more pragmatic solution would be to seek to repurpose existing drugs, particularly those that might suppress the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19. Montelukast is a cysteinyl leukotriene receptor antagonist licensed to treat asthma and allergic rhinitis. It has been shown to diminish pulmonary response to antigen, tissue eosinophilia and IL-5 expression in inflammatory cells. It has also been shown to decrease elevated levels of IL-1β and IL8 in humans with viral upper respiratory tract infections compared with placebo-treated patients. In addition, in silico studies have demonstrated a high binding affinity of the montelukast molecule to the terminal site of the virus's main protease enzyme which is needed for virus RNA synthesis and replication. Montelukast, which is cheap, safe and widely available would appear to have the potential to be an ideal candidate drug for clinical trials, particularly in early stage disease before irreparable tissue damage has already occurred. HYPOTHESIS: Through a direct anti-viral effect, or by suppression of heightened cytokine release in response to SARS-CoV-2, montelukast will reduce the severity of immune-mediated multiorgan damage resulting from COVID-19, particularly in patients with central obesity and metabolic syndrome.

Media Type:

Electronic Article

Year of Publication:

2020

Contained In:

Medical hypotheses - Vol. 143 (2020), p. 109883

Language:

English

Contributors:

Almerie, Muhammad Qutayba
Kerrigan, David Daniel

Links:

Volltext

Keywords:

*Betacoronavirus
3C-like proteinase, Coronavirus
Acetates
Antiviral Agents
Coronavirus Infections
Cysteine Endopeptidases
Cytokine Release Syndrome
Drug Repositioning
EC 3.4.22.-
Humans
Immunologic Factors
Inflammation
Journal Article
Leukotriene Antagonists
MHM278SD3E
Montelukast
Obesity
Pandemics
Pneumonia, Viral
Quinolines
Viral Nonstructural Proteins

Notes:

Date Completed 13.10.2020

Date Revised 13.10.2020

published: Print-Electronic

Citation Status MEDLINE

Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Physical Description:

Online-Ressource

doi:

10.1016/j.mehy.2020.109883

PMID:

32492562

PPN (Catalogue-ID):

NLM311615899