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Review
. 2021 Aug 5:904:174196.
doi: 10.1016/j.ejphar.2021.174196. Epub 2021 May 15.

Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity

Hayder M Al-Kuraishy  1 , Ali I Al-Gareeb  2 , Yaaser Q Almulaiky  3 , Natália Cruz-Martins  4 , Gaber El-Saber Batiha  5
Affiliations
Review

Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity

Hayder M Al-Kuraishy et al. Eur J Pharmacol. .

Abstract

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction with angiotensin converting enzyme 2 (ACE2) receptors, highly expressed in lung type II alveolar cells and other tissues, like heart, pancreas, brain, and vascular endothelium. This review aimed to elucidate the potential role of leukotrienes (LTs) in the pathogenesis and clinical presentation of SARS-CoV-2 infection, and to reveal the critical role of LT pathway receptor antagonists and inhibitors in Covid-19 management. A literature search was done in PubMed, Scopus, Web of Science and Google Scholar databases to find the potential role of montelukast and other LT inhibitors in the management of pulmonary and extra-pulmonary manifestations triggered by SARS-CoV-2. Data obtained so far underline that pulmonary and extra-pulmonary manifestations in Covid-19 are attributed to a direct effect of SARS-CoV-2 in expressed ACE2 receptors or indirectly through NF-κB dependent induction of a cytokine storm. Montelukast can ameliorate extra-pulmonary manifestations in Covid-19 either directly through blocking of Cys-LTRs in different organs or indirectly through inhibition of the NF-κB signaling pathway.

Keywords: Extrapulmonary manifestations; Leukotriene; Montelukast; SARS-CoV-2.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Leukotriene pathway. COX: cyclooxygenase, 5-LO: 5-lipoxygenase, 5-HPETE: 5-hydroperoxyeicosatetraenoic acid, LTA4: leukotriene A4, LTB4: leukotriene B4, LTC4: leukotriene C4, LTD4: leukotriene D4, LTE4: leukotriene E4.
Fig. 2
Fig. 2
The interaction between SARS-CoV-2 and leukotriene pathway in Covid-19. AA: Arachidonic acid; ALI: acute lung injury; ARDS: acute respiratory distress syndrome; Cys-LTs: cysteinyl-leukotrienes; Cys-LTR: cysteinyl-leukotriene receptor; LTBR: leukotriene B receptor.
Fig. 3
Fig. 3
Role of the Cys-LTR antagonist montelukast in the mitigation of extrapulmonary manifestations in Covid-19.
See this image and copyright information in PMC

References

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