Sebastián-Martín Alba, Sánchez Belén G, Mora-Rodríguez José M, Bort Alicia, Díaz-Laviada Inés
University of Alcalá, School of Medicine and Health Sciences, Department of Systems Biology, Biochemistry and Molecular Biology Unit, 28871 Madrid, Spain.
Department of Comparative Medicine, School of Medicine, Yale University, New Haven, CT 06519, USA.
Biomedicines. 2022 Aug 19;10(8):2026. doi: 10.3390/biomedicines10082026.
DPP4/CD26 is a single-pass transmembrane protein with multiple functions on glycemic control, cell migration and proliferation, and the immune system, among others. It has recently acquired an especial relevance due to the possibility to act as a receptor or co-receptor for SARS-CoV-2, as it has been already demonstrated for other coronaviruses. In this review, we analyze the evidence for the role of DPP4 on COVID-19 risk and clinical outcome, and its contribution to COVID-19 physiopathology. Due to the pathogenetic links between COVID-19 and diabetes mellitus and the hyperinflammatory response, with the hallmark cytokine storm developed very often during the disease, we dive deep into the functions of DPP4 on carbohydrate metabolism and immune system regulation. We show that the broad spectrum of functions regulated by DPP4 is performed both as a protease enzyme, as well as an interacting partner of other molecules on the cell surface. In addition, we provide an update of the DPP4 inhibitors approved by the EMA and/or the FDA, together with the newfangled approval of generic drugs (in 2021 and 2022). This review will also cover the effects of DPP4 inhibitors (i.e., gliptins) on the progression of SARS-CoV-2 infection, showing the role of DPP4 in this disturbing disease.
二肽基肽酶4/CD26（DPP4/CD26）是一种单次跨膜蛋白，在血糖控制、细胞迁移与增殖以及免疫系统等方面具有多种功能。由于它有可能作为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的受体或共受体，最近它受到了特别关注，其他冠状病毒已有相关证明。在这篇综述中，我们分析了DPP4在2019冠状病毒病（COVID-19）风险和临床结局中的作用证据，及其对COVID-19病理生理学的贡献。鉴于COVID-19与糖尿病之间的发病机制联系以及炎症反应过度，且该病期间常出现标志性的细胞因子风暴，我们深入探讨了DPP4在碳水化合物代谢和免疫系统调节中的功能。我们表明，DPP4调节的广泛功能既是作为一种蛋白酶发挥作用，也是作为细胞表面其他分子的相互作用伴侣发挥作用。此外，我们提供了欧洲药品管理局（EMA）和/或美国食品药品监督管理局（FDA）批准的DPP4抑制剂的最新情况，以及仿制药的最新批准情况（2021年和2022年）。这篇综述还将涵盖DPP4抑制剂（即格列汀类药物）对SARS-CoV-2感染进展的影响，展示DPP4在这种令人不安的疾病中的作用。
