Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China.
Department of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, China.
Br J Pharmacol. 2023 Oct;180(19):2455-2481. doi: 10.1111/bph.16187. Epub 2023 Aug 4.
Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. The COVID-19 pandemic began in March 2020 and has wrought havoc on health and economic systems worldwide. Efficacious treatment for COVID-19 is lacking: Only preventive measures as well as symptomatic and supportive care are available. Preclinical and clinical studies have indicated that lysosomal cathepsins might contribute to the pathogenesis and disease outcome of COVID-19. Here, we discuss cutting-edge evidence on the pathological roles of cathepsins in SARS-CoV-2 infection, host immune dysregulations, and the possible underlying mechanisms. Cathepsins are attractive drug targets because of their defined substrate-binding pockets, which can be exploited as binding sites for pharmaceutical enzyme inhibitors. Accordingly, the potential modulatory strategies of cathepsin activity are discussed. These insights could shed light on the development of cathepsin-based interventions for COVID-19.
新型冠状病毒病（COVID-19）是由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）感染引起的。COVID-19 大流行始于 2020 年 3 月，给全球的卫生和经济系统带来了严重破坏。目前还缺乏有效的 COVID-19 治疗方法：仅能提供预防措施以及对症和支持性护理。临床前和临床研究表明，溶酶体组织蛋白酶可能有助于 COVID-19 的发病机制和疾病结局。在这里，我们讨论了有关组织蛋白酶在 SARS-CoV-2 感染、宿主免疫失调以及可能的潜在机制中的病理作用的最新证据。由于其具有明确的底物结合口袋，组织蛋白酶是有吸引力的药物靶点，可将其用作药物酶抑制剂的结合位点。因此，讨论了组织蛋白酶活性的潜在调节策略。这些见解可以为基于组织蛋白酶的 COVID-19 干预措施的开发提供参考。
