Unit of Endocrinology and Diabetes, Department of Medicine, Campus Bio-Medico, University of Rome, Rome, Italy.
Centre for Immunobiology, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
Diabetes Metab Res Rev. 2020 Nov;36(8):e3330. doi: 10.1002/dmrr.3330. Epub 2020 Jun 3.
Dipeptidyl peptidase 4 (DPP4), also known as cluster of differentiation 26 (CD26), is a serine exopeptidase expressed ubiquitously in several tissues, including but not limited to lung, kidney, liver, gut, and immune cells. The question has been raised on whether DPP4 modulation or inhibition may prevent infection and/or progression of the COVID-19. A docked complex model of the SARS-CoV-2 spike glycoprotein and DPP4 has been proposed, showing a large interface between the proteins and proposing close similarity with other coronaviruses using DPP4 as functional receptor. In absence of experimental validation, these data should be interpreted with caution. Nevertheless, this observation may rise the question on whether DPP4 is directly involved in SARS-CoV-2 cell adhesion/virulence, and whether DPP4 inhibition might be a therapeutic strategy for preventing infection. Although a direct involvement of DPP4 in SARS-CoV-2 infection needs to be clarified, there is also evidence suggesting that DPP4 inhibitors modulate inflammation and exert anti-fibrotic activity. These properties may be of potential use for halting progression to the hyperinflammatory state associated with severe COVID-19. Taken together these findings may suggest a potential role for DPP4 inhibition or modulation in one or more steps of COVID-19 immunopathogenesis.
二肽基肽酶 4（DPP4），也被称为分化群 26（CD26），是一种丝氨酸外肽酶，广泛表达于多种组织中，包括但不限于肺、肾、肝、肠道和免疫细胞。人们提出了这样一个问题，即 DPP4 的调节或抑制是否可以预防 COVID-19 的感染和/或进展。已经提出了 SARS-CoV-2 刺突糖蛋白和 DPP4 的对接复合物模型，显示出两种蛋白质之间存在较大的界面，并使用 DPP4 作为功能性受体，提出了与其他冠状病毒的相似性。在缺乏实验验证的情况下，这些数据应谨慎解释。尽管如此，这一观察结果可能引发了一个问题，即 DPP4 是否直接参与 SARS-CoV-2 的细胞黏附和毒力，以及抑制 DPP4 是否可能成为预防感染的一种治疗策略。虽然 DPP4 是否直接参与 SARS-CoV-2 感染仍需澄清，但也有证据表明 DPP4 抑制剂可调节炎症并发挥抗纤维化作用。这些特性可能对阻止与严重 COVID-19 相关的过度炎症状态的进展有用。综上所述，这些发现可能表明 DPP4 的抑制或调节在 COVID-19 的免疫发病机制的一个或多个步骤中可能具有潜在作用。
