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

Abstract

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).

Graphical abstract

Figure 1

Antagonism of cysteinyl leukotriene receptor 1 by montelukast attenuates the activation of nuclear factor (NF)-κB transcription factor p50-p65, decreasing downstream gene expression and production of proinflammatory mediators, and mitigating cytokine storm syndrome. Abbreviations: 5-LOX, 5-lipoxygenase; Cys-LTs, cysteinyl leukotrienes; LTA4, leukotriene A4; LTB4, leukotriene B4; PLA2, phospholipase A2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.