Aigner Ludwig, Pietrantonio Frank, Bessa de Sousa Diana Marisa, Michael Johanna, Schuster Daniela, Reitsamer Herbert Anton, Zerbe Horst, Studnicka Michael
Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria.
Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, Salzburg, Austria.
Front Mol Biosci. 2020 Dec 17;7:610132. doi: 10.3389/fmolb.2020.610132. eCollection 2020.
The emergence and global impact of COVID-19 has focused the scientific and medical community on the pivotal influential role of respiratory viruses as causes of severe pneumonia, on the understanding of the underlying pathomechanisms, and on potential treatment for COVID-19. The latter concentrates on different strategies: (i) antiviral treatments to limit the entry of the virus into the cell and its propagation, (ii) anti-inflammatory treatment to reduce the impact of COVID-19 associated inflammation and cytokine storm, (iii) treatment using cardiovascular medication to reduce COVID-19 associated thrombosis and vascular damage, and (iv) treatment to reduce the COVID-19 associated lung injury. Ideally, effective COVID-19 treatment should target as many of these mechanisms as possible arguing for the search of common denominators as potential drug targets. Leukotrienes and their receptors qualify as such targets: they are lipid mediators of inflammation and tissue damage and well-established targets in respiratory diseases like asthma. Besides their role in inflammation, they are involved in various other aspects of lung pathologies like vascular damage, thrombosis, and fibrotic response, in brain and retinal damages, and in cardiovascular disease. In consequence, leukotriene receptor antagonists might be potential candidates for COVID-19 therapeutics. This review summarizes the current knowledge on the potential involvement of leukotrienes in COVID-19, and the rational for the use of the leukotriene receptor antagonist montelukast as a COVID-19 therapeutic.
新型冠状病毒肺炎(COVID-19)的出现及其全球影响,使科学界和医学界聚焦于呼吸道病毒作为重症肺炎病因的关键影响作用、对潜在发病机制的理解以及针对COVID-19的潜在治疗方法。后者集中在不同策略上:(i)抗病毒治疗以限制病毒进入细胞及其增殖;(ii)抗炎治疗以减轻与COVID-19相关的炎症和细胞因子风暴的影响;(iii)使用心血管药物治疗以减少与COVID-19相关的血栓形成和血管损伤;(iv)治疗以减轻与COVID-19相关的肺损伤。理想情况下,有效的COVID-19治疗应针对尽可能多的这些机制,这支持寻找作为潜在药物靶点的共同特征。白三烯及其受体符合此类靶点:它们是炎症和组织损伤的脂质介质,也是哮喘等呼吸道疾病中已确立的靶点。除了在炎症中的作用外,它们还参与肺部病理的其他各个方面,如血管损伤、血栓形成和纤维化反应、脑和视网膜损伤以及心血管疾病。因此,白三烯受体拮抗剂可能是COVID-19治疗的潜在候选药物。本综述总结了目前关于白三烯在COVID-19中潜在作用的知识,以及使用白三烯受体拮抗剂孟鲁司特作为COVID-19治疗药物的理论依据。