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Updated: Dec 23, 2025

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SARS-CoV-2 and DPP4 inhibition: Is it time to pray for Janus Bifrons?

Dario Pitocco1, Linda Tartaglione1, Luca Viti1

  • 1Diabetes Care Unit, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.

Diabetes Research and Clinical Practice
|April 27, 2020
PubMed

Insights

DPP4 inhibition is not a viable strategy for mitigating COVID-19 severity. Research indicates a lack of SARS-CoV-2 binding to DPP4 and potential protective roles, making it an implausible therapeutic target.

Area of Science:

  • Virology
  • Endocrinology
  • Infectious Diseases

Background:

  • Diabetes is a known risk factor for severe COVID-19 outcomes.
  • Dipeptidyl peptidase-4 (DPP4) inhibitors are used to treat type 2 diabetes.
  • DPP4 inhibition was hypothesized as a potential therapeutic strategy for COVID-19 complications.

Purpose of the Study:

  • To evaluate the plausibility of DPP4 inhibition as a therapeutic approach for COVID-19.
  • To analyze the interaction between SARS-CoV-2 and DPP4.
  • To assess the role of DPP4 in coronavirus infections.

Main Methods:

  • Literature review and analysis of existing research on DPP4 and coronaviruses.
  • Examination of evidence regarding SARS-CoV-2 binding to DPP4.
  • Evaluation of the role of soluble DPP4 (sDPP4) in MERS-CoV infection.

Main Results:

  • No clear demonstration of SARS-CoV-2 binding to DPP4 was found.
  • Evidence suggests a possible protective role for sDPP4 in Middle East Respiratory Syndrome (MERS-CoV).
  • DPP4 is known to be inhibited and downregulated by other viruses like HIV-1 and MERS-CoV.

Conclusions:

  • DPP4 inhibition is not currently considered a plausible approach to mitigate COVID-19.
  • The complex role of DPP4 in viral infections and lack of direct SARS-CoV-2 interaction support this conclusion.
  • Further research is needed to understand DPP4's role in coronavirus tropism.
Keywords:
ACE 2COVID 19DPP4Diabetes

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