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 《-》

Taming the cytokine storm: repurposing montelukast for the attenuation and prophylaxis of severe COVID-19 symptoms.

As a result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, a clinical complication can arise that is characterized by a hyperinflammatory cytokine profile, often termed a 'cytokine storm'. A protein complex (nuclear factor kappa-light-chain-enhancer of activated B cells; NF-κB) is intricately involved in regulating inflammation and the immune response following viral infections, with a reduction in cytokine production often observed following a decrease in NF-κB activity. An approved asthma drug, montelukast, has been found to modulate the activity of NF-κB, and result in a corresponding decrease in proinflammatory mediators. Herein, we hypothesize that repurposing montelukast to suppress NF-κB activation will result in an attenuation of proinflammatory mediators and a decrease in cytokine production, thereby leading to a reduction in symptom severity and to improved clinical outcomes in patients with Coronavirus 2019 (COVID-19).

Sanghai N ，Tranmer GK 《-》

Purposing Saikosaponins for the treatment of COVID-19.

Bahbah EI ，Negida A ，Nabet MS 《-》

In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection.

Martorana A ，Gentile C ，Lauria A 《Viruses-Basel》