PDF(Pubmed)
Abstract：
Proteases are produced and released in the mucosal cells of the respiratory tract and have important physiological functions, for example, maintaining airway humidification to allow proper gas exchange. The infectious mechanism of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), takes advantage of host proteases in two ways: to change the spatial conformation of the spike (S) protein via endoproteolysis (e.g., transmembrane serine protease type 2 (TMPRSS2)) and as a target to anchor to epithelial cells (e.g., angiotensin-converting enzyme 2 (ACE2)). This infectious process leads to an imbalance in the mucosa between the release and action of proteases versus regulation by anti-proteases, which contributes to the exacerbation of the inflammatory and prothrombotic response in COVID-19. In this article, we describe the most important proteases that are affected in COVID-19, and how their overactivation affects the three main physiological systems in which they participate: the complement system and the kinin-kallikrein system (KKS), which both form part of the contact system of innate immunity, and the renin-angiotensin-aldosterone system (RAAS). We aim to elucidate the pathophysiological bases of COVID-19 in the context of the imbalance between the action of proteases and anti-proteases to understand the mechanism of aprotinin action (a panprotease inhibitor). In a second-part review, titled \"Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions\", we explain in depth the pharmacodynamics, pharmacokinetics, toxicity, and use of aprotinin as an antiviral drug.
摘要：
蛋白酶在呼吸道粘膜细胞中产生和释放，具有重要的生理功能，例如,保持气道加湿以允许适当的气体交换。严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的感染机制,导致2019年冠状病毒病（COVID-19），以两种方式利用宿主蛋白酶：通过内蛋白水解改变刺突（S）蛋白的空间构象（例如，跨膜丝氨酸蛋白酶2型（TMPRSS2）），并作为锚定到上皮细胞的靶标（例如，血管紧张素转换酶2（ACE2）。这种感染过程导致粘膜在蛋白酶的释放和作用与抗蛋白酶的调节之间的不平衡。这有助于COVID-19炎症和血栓前反应的恶化。在这篇文章中,我们描述了在COVID-19中受影响的最重要的蛋白酶，以及它们的过度激活如何影响它们参与的三个主要生理系统：补体系统和激肽-激肽释放酶系统（KKS），两者都是先天免疫接触系统的一部分，和肾素-血管紧张素-醛固酮系统（RAAS）。我们的目的是在蛋白酶和抗蛋白酶作用不平衡的背景下阐明COVID-19的病理生理基础，以了解抑肽酶（一种全蛋白酶抑制剂）的作用机制。在第二部分审查中，题为“抑肽酶（II）：治疗COVID-19和其他病毒疾病的吸入给药”，我们深入解释药效学，药代动力学，毒性,使用抑肽酶作为抗病毒药物。
