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COVID-19 and comorbidities: A role for dipeptidyl peptidase 4 (DPP4) in disease severity?

Lookup NU author(s): Emeritus Professor Margaret Bassendine, Dr Simon Bridge



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd. 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.

Publication metadata

Author(s): Bassendine MF, Bridge SH, McCaughan GW, Gorrell MD

Publication type: Review

Publication status: Published

Journal: Journal of Diabetes

Year: 2020

Volume: 12

Issue: 9

Pages: 649-658

Print publication date: 01/09/2020

Online publication date: 11/05/2020

Acceptance date: 08/05/2020

ISSN (print): 1753-0393

ISSN (electronic): 1753-0407

Publisher: John Wiley and Sons Inc.


DOI: 10.1111/1753-0407.13052

PubMed id: 32394639