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

  • Solerte, Sebastiano Bruno1
  • Di Sabatino, Antonio2
  • Galli, Massimo3, 4
  • Fiorina, Paolo5, 6, 7
  • 1 University of Pavia, Pavia, Italy , Pavia (Italy)
  • 2 University of Pavia and IRCCS Policlinico San Matteo, Pavia, Italy , Pavia (Italy)
  • 3 University of Milan, Milan, Italy , Milan (Italy)
  • 4 ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy , Milan (Italy)
  • 5 Università Degli Studi di Milano, Milan, Italy , Milan (Italy)
  • 6 ASST Fatebenefratelli-Sacco, Milan, Italy , Milan (Italy)
  • 7 Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA , Boston (United States)
Published Article
Acta Diabetologica
Springer Milan
Publication Date
Jun 06, 2020
DOI: 10.1007/s00592-020-01539-z
Springer Nature


AimsSARS–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.MethodsVirus 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.ResultsThe 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.ConclusionsThe 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.

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