Abstract
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.
Highlights
The rampant new clinical infectious disease that emerged in late 2019 and rapidly became a world pandemic is caused by a novel betacoronavirus; the disease is called COVID-19 (Coronavirus Disease 2019)
This review focuses on dipeptidyl peptidase 4 (DPP4) as its expression may be a factor in determining the balance between virus and host in COVID-19 and can potentially be linked to some of the known comorbidities
type 2 diabetes mellitus (T2DM) has itself been called a pandemic with around 415 million adults living with the disease
Summary
The rampant new clinical infectious disease that emerged in late 2019 and rapidly became a world pandemic is caused by a novel betacoronavirus; the disease is called COVID-19 (Coronavirus Disease 2019). Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2; recent modeling of the structure of SARS-CoV-2 spike glycoprotein, which mediates viral-host-cell entry, predicts interactions with dipeptidyl peptidase 4 (DPP4) in addition to angiotensin-converting enzyme 2.
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