Possible Therapeutic Potential of Cysteinyl Leukotriene Receptor Antagonist Montelukast in Treatment of SARS-CoV-2-Induced COVID-19.

The coronavirus disease-19 (COVID-19) pandemic is a serious devastating disease and has posed a global health emergency. So far, there is not any specific therapy approved till date to control the clinical symptoms of the disease. Remdesivir has been approved by the FDA as an emergency clinical therapy. But it may not be effective alone to control the disease as it can only control the viral replication in the host. This article summarizes the possible therapeutic potential and benefits of using montelukast, a cysteinyl leukotriene 1 (CysLT1) receptor antagonist, to control COVID-19 pathophysiology. Montelukast has shown anti-inflammatory effects, reduced cytokine production, improvement in post-infection cough production and other lung complications. Key Messages: Recent reports clearly indicate a distinct role of CysLT-regulated cytokines and immunological signaling in COVID-19. Thus, montelukast may have a clinical potential to control lung pathology during COVID-19.

Dey M ，Singh RK 《-》

The Leukotriene Receptor Antagonist Montelukast Reduces Alpha-Synuclein Load and Restores Memory in an Animal Model of Dementia with Lewy Bodies.

Marschallinger J ，Altendorfer B ，Rockenstein E ，Holztrattner M ，Garnweidner-Raith J ，Pillichshammer N ，Leister I ，Hutter-Paier B ，Strempfl K ，Unger MS ，Chishty M ，Felder T ，Johnson M ，Attems J ，Masliah E ，Aigner L ... -  《-》

Montelukast and Coronavirus Disease 2019: A Scoping Review.

Sharifinejad N ，Sharafian S ，Salekmoghadam S ，Tavakol M ，Qorbani M ... -  《-》

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

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.

Almerie MQ ，Kerrigan DD 《-》

As a potential treatment of COVID-19: Montelukast.

It has been hypothesized that Montelukast, a cysteinyl leukotriene (cysLT) receptor antagonist, with effects of anti-inflammatory, suppress oxidative stress and reduce affect cytokine production, may limited progression of the disease on COVID-19 infection.

Fidan C ，Aydoğdu A 《-》