Laboratory of Molecular Neurovirology, Faculty of Health Science, University of Brasília, Brasilia, Brazil.
Rev Med Virol. 2021 Mar;31(2):e2157. doi: 10.1002/rmv.2157. Epub 2020 Aug 26.
Understanding Covid-19 pathophysiology is crucial for a better understanding of the disease and development of more effective treatments. Alpha-1-antitrypsin (A1AT) is a constitutive tissue protector with antiviral and anti-inflammatory properties. A1AT inhibits SARS-CoV-2 infection and two of the most important proteases in the pathophysiology of Covid-19: the transmembrane serine protease 2 (TMPRSS2) and the disintegrin and metalloproteinase 17 (ADAM17). It also inhibits the activity of inflammatory molecules, such as IL-8, TNF-α, and neutrophil elastase (NE). TMPRSS2 is essential for SARS-CoV-2-S protein priming and viral infection. ADAM17 mediates ACE2, IL-6R, and TNF-α shedding. ACE2 is the SARS-CoV-2 entry receptor and a key component for the balance of the renin-angiotensin system, inflammation, vascular permeability, and pulmonary homeostasis. In addition, clinical findings indicate that A1AT levels might be important in defining Covid-19 outcomes, potentially partially explaining associations with air pollution and with diabetes. In this review, we focused on the interplay between A1AT with TMPRSS2, ADAM17 and immune molecules, and the role of A1AT in the pathophysiology of Covid-19, opening new avenues for investigating effective treatments.
了解新冠病毒的病理生理学对于更好地理解该疾病和开发更有效的治疗方法至关重要。α-1-抗胰蛋白酶（A1AT）是一种组成性组织保护剂，具有抗病毒和抗炎特性。A1AT 可抑制 SARS-CoV-2 感染以及新冠病毒病理生理学中两种最重要的蛋白酶：跨膜丝氨酸蛋白酶 2（TMPRSS2）和解整合素金属蛋白酶 17（ADAM17）。它还可抑制炎症分子的活性，如 IL-8、TNF-α 和中性粒细胞弹性蛋白酶（NE）。TMPRSS2 是 SARS-CoV-2-S 蛋白引发和病毒感染所必需的。ADAM17 介导 ACE2、IL-6R 和 TNF-α 的脱落。ACE2 是 SARS-CoV-2 的进入受体，也是肾素-血管紧张素系统、炎症、血管通透性和肺内平衡的关键组成部分。此外，临床研究结果表明，A1AT 水平可能对新冠病毒的预后具有重要意义，可能部分解释了其与空气污染和糖尿病之间的关联。在这篇综述中，我们重点探讨了 A1AT 与 TMPRSS2、ADAM17 和免疫分子之间的相互作用，以及 A1AT 在新冠病毒病理生理学中的作用，为研究有效的治疗方法开辟了新的途径。
