The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome (MERS-CoV), which cause acute respiratory distress syndrome and case fatalities. COVID-19 disease severity is worse in older obese patients with comorbidities such as diabetes, hypertension, cardiovascular disease, and chronic lung disease. Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS-CoV binds to the metalloprotease angiotensin-converting enzyme 2 (ACE2), MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. DPP4 is a ubiquitous membrane-bound aminopeptidase that circulates in plasma; it is multifunctional with roles in nutrition, metabolism, and immune and endocrine systems. DPP4 activity differentially regulates glucose homeostasis and inflammation via its enzymatic activity and nonenzymatic immunomodulatory effects. The importance of DPP4 for the medical community has been highlighted by the approval of DPP4 inhibitors, or gliptins, for the treatment of type 2 diabetes mellitus. This review discusses the dysregulation of DPP4 in COVID-19 comorbid conditions; DPP4 activity is higher in older individuals and increased plasma DPP4 is a predictor of the onset of metabolic syndrome. DPP4 upregulation may be a determinant of COVID-19 disease severity, which creates interest regarding the use of gliptins in management of COVID-19. Also, knowledge of the chemistry and biology of DPP4 could be utilized to develop novel therapies to block viral entry of some betacoronaviruses, potentially including SARS-CoV-2.
摘要: 2019年新冠肺炎冠状病毒大流行是由一种新型β新冠状病毒-严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的, 类似于SARS-CoV和中东呼吸综合征(MERS-CoV), 可引起急性呼吸窘迫综合征和死亡。新冠肺炎病的严重程度在患有糖尿病, 高血压, 心血管疾病和慢性肺部疾病的老年肥胖患者中更严重。β冠状病毒结合并进入细胞是通过它们的表面刺状糖蛋白；SARS-CoV是与金属蛋白酶血管紧张素转换酶2(ACE2)结合, 而MERS-CoV利用二肽肽酶4(DPP4)进入细胞。最近对SARS-CoV-2刺激性糖蛋白结构的模拟, 预测除了ACE2之外, 它还可以与人DPP4相互作用。DPP4是一种无处不在的膜结合型氨基肽酶, 在血浆中循环, 具有多种功能, 在营养, 代谢, 免疫和内分泌系统中发挥作用。DPP4通过其酶活性和非酶免疫调节作用, 调节葡萄糖稳态和炎症。DPP4抑制剂或格列普汀被批准用于治疗2型糖尿病, 这突显了DPP4对医学界的重要性。本文就新冠肺炎合并疾病时DPP4的异常调节进行综述。老年人DPP4活性较高, 血浆DPP4升高是代谢综合征发病的预测因子。DPP4上调可能是新冠肺炎疾病严重程度的决定因素, 这引起了人们对格列普汀在新冠肺炎治疗中使用的兴趣。此外, DPP4的化学和生物学知识可以用来开发新的疗法, 阻止一些β冠状病毒如SARS-CoV-2等入侵体内。.
Keywords: COVID-19; SARS-CoV-2; case fatality; dipeptidyl-peptidase IV inhibitors; metabolic syndrome; 严重急性呼吸综合征冠状病毒2型; 二肽基肽酶IV抑制剂; 代谢综合征; 新冠肺炎; 病例死亡.
© 2020 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.