Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil.
Division of Nephrology, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
Front Cell Infect Microbiol. 2020 Dec 8;10:589505. doi: 10.3389/fcimb.2020.589505. eCollection 2020.
The coronavirus disease 2019 (COVID-19) pandemics is a challenge without precedent for the modern science. Acute Respiratory Discomfort Syndrome (ARDS) is the most common immunopathological event in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. Fast lung deterioration results of cytokine storm determined by a robust immunological response leading to ARDS and multiple organ failure. Here, we show cysteine protease Cathepsin L (CatL) involvement with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 from different points of view. CatL is a lysosomal enzyme that participates in numerous physiological processes, including apoptosis, antigen processing, and extracellular matrix remodeling. CatL is implicated in pathological conditions like invasion and metastasis of tumors, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, viral infection, and other diseases. CatL expression is up-regulated during chronic inflammation and is involved in degrading extracellular matrix, an important process for SARS-CoV-2 to enter host cells. In addition, CatL is probably involved in processing SARS-CoV-2 spike protein. As its inhibition is detrimental to SARS-CoV-2 infection and possibly exit from cells during late stages of infection, CatL could have been considered a valuable therapeutic target. Therefore, we describe here some drugs already in the market with potential CatL inhibiting capacity that could be used to treat COVID-19 patients. In addition, we discuss the possible role of host genetics in the etiology and spreading of the disease.
2019 年冠状病毒病（COVID-19）大流行是现代科学前所未有的挑战。急性呼吸窘迫综合征（ARDS）是 SARS-CoV-2、SARS-CoV 和 MERS-CoV 感染中最常见的免疫病理学事件。快速的肺部恶化是由强大的免疫反应引起的细胞因子风暴导致的 ARDS 和多器官衰竭的结果。在这里，我们从不同的角度展示半胱氨酸蛋白酶组织蛋白酶 L（CatL）与严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）和 COVID-19 的关系。CatL 是一种溶酶体酶，参与许多生理过程，包括细胞凋亡、抗原加工和细胞外基质重塑。CatL 参与肿瘤的侵袭和转移、炎症状态、动脉粥样硬化、肾脏疾病、糖尿病、骨疾病、病毒感染和其他疾病等病理状况。CatL 在慢性炎症期间表达上调，并参与降解细胞外基质，这是 SARS-CoV-2 进入宿主细胞的重要过程。此外，CatL 可能参与 SARS-CoV-2 刺突蛋白的加工。由于其抑制作用对 SARS-CoV-2 感染有害，并且可能在感染后期从细胞中逸出，因此 CatL 可能被认为是一个有价值的治疗靶点。因此，我们在这里描述了一些已经上市的具有潜在 CatL 抑制能力的药物，这些药物可用于治疗 COVID-19 患者。此外，我们还讨论了宿主遗传因素在疾病病因和传播中的可能作用。
