Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19

Abstract

Aims SARS-CoV-2 causes severe respiratory syndrome (COVID-19) with high mortality due to a direct cytotoxic viral effect and a severe systemic inflammation. We are herein discussing a possible novel therapeutic tool for COVID-19. Methods Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS-CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS-Co-V, namely the DPP4/CD26 receptor. The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar. Results The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. Conclusions The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.

Circulating levels of soluble Dipeptidylpeptidase-4 are reduced in human subjects hospitalized for severe COVID-19 infections

“…The results from the functional assays showing that ACE2 but not DPP-4 is the important membrane bound protein for virus internalization might question these hypotheses. However, several researchers (see [16] for a summary) have speculated about the role of DPP-4 as an important co-receptor of COVID-19. The fact (1) that the S1 domain of COVID-19 spike glycoprotein is able to interact with DPP-4, (2) that sDPP-4 is reduced in COVID-19 patients as in MERS-CoV infected subjects and (3) that obesity and type 2 diabetes are major risk factor for a severe course of COVID-19, from our point of view represent enough scientific evidence for further research into the potential role of circulating sDPP-4 in COVID-19 acute and long-term metabolic complications.…”

COVID-19: molecular targets, drug repurposing and new avenues for drug discovery

“…(152,153,155,156) In principle, these inhibitors could be beneficial for type 2 diabetes patients (or even without diabetes) with COVID-19 since it could potentially block virus cell entry/replication, as well suppress inflammatory response. (152,155) However, there is not enough evidence yet to prove this hypothesis. (152,153,156) Repositioning studies in progress for the treatment of COVID-19…”

Efficacy and safety of DPP-4 inhibitor in the treatment of patients with COVID-19 combined with diabetes mellitus

“…to inhibit the activity of DPP4/CD26 may be an effective weapon to block the host CD26 receptor, thereby blocking SARS CoV- 2 Enter T cells to prevent infection of COVID-19. [ 9 ] Furthermore, as a class of oral hypoglycemic agents, DPP-4 inhibitors can effectively reduce glycosylated hemoglobin. Therefore, the researches of DPP-4 inhibitors have exciting potential for diabetic patients infected with COVID-19.…”