New research suggests that the DPP4 enzyme could be a drug target for COVID-19 and DPP4 inhibitors could therefore treat the coronavirus.
In a newly published commentary, University of Miami Miller School of Medicine professor and endocrinologist Dr Gianluca Iacobellis, suggests the DPP4 enzyme, also known as CD26 (cluster of differentiation 26), presents an interesting target for research and DPP4 inhibitors could help some COVID-19 patients.
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DPP4 is found throughout the body, but its activity is only partially understood. The enzyme plays significant roles in inflammatory responses and insulin regulation. DPP4 inhibitors increase insulin and GLP-1 secretion and are commonly prescribed for people suffering from type 2 diabetes.
Data from Wuhan and Italy have shown that type 2 diabetes patients have higher mortality and higher intensive care unit (ICU) admission rates. Building on previous research, conducted on earlier coronaviruses, Iacobellis explains why he believes the enzyme may play a significant role in these outcomes by interfering with the immune response.
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“The body is overreacting with this inflammatory response to the virus,” said Iacobellis. “This could be partially mediated by DPP4. The virus binds to the enzyme and the enzymatic activity of DPP4 overexpresses inflammatory cytokines, exaggerating the inflammatory response. Previous studies, of severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS), showed that, if you blocked DPP4 activity, there was a reduction in the inflammatory response. This could ameliorate the immune response to the virus.”
Iacobellis notes that clinicians will need more data before embracing DPP4 inhibitors to treat COVID-19 patients. However, he also highlights that early evidence reveals these drugs reduce inflammation.
How the DPP4 enzyme and COVID-19 interact [credit: Dr Gianluca Iacobellis].
“Starting with diabetes patients, we should be conducting randomised studies to test whether treating those with mild or moderate symptoms improves outcomes,” said Iacobellis. “These drugs are well tolerated and may provide therapeutic benefit.”
Iacobellis concluded: “We potentially have a mechanism for how the virus is getting into the body… We potentially have a way we can partially inhibit that mechanism. We should consider clinical trials for DPP4 for patients who have mild or moderate COVID-19 with type 2 diabetes.”
The results were published in Diabetes Research and Clinical Practice.