Scientists across the world are working towards learning more about the invading mechanism of the deadly SARS-CoV-2 coronavirus in order to halt its spread. Also, some patients with pre-existing illnesses are at a larger risk due to COVID-19. A new paper suggests that targeting a particular enzyme in the body could resolve both concerns.

According to a commentary by Dr. Gianluca Iacobellis from the Miller School of Medicine, suppressing an enzyme known as DPP4 could benefit COVID-19 patients suffering from type 2 diabetes. The enzyme has been proven to play an important role in the binding process of other potent coronaviruses that cause Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS).

"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," said Dr. Iacobellis, in a statement.

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What is DPP4?

DPP4 stands for Dipeptidyl peptidase-4, and is found throughout the human body. Its activity, however, is only partially comprehended, although it is known to play an important role in the insulin regulation and inflammatory response of the body.

Drugs known as DPP4-inhibitors or gliptins, are prescribed to increase the levels of essential hormones in individuals afflicted with type 2 diabetes. Some of these hormones include insulin and GLP-1, which regulate blood sugar levels in the body.

Diabetics at a larger risk

As the pandemic has progressed, studies have shown that patients suffering from diabetes form a part of the high-risk population. According to data from Italy and Wuhan — two of the worst affected regions in the world — higher ICU admission rates and mortality have been observed among patients with type 2 diabetes.

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Novel Coronavirus SARS-CoV-2 Wikimedia Commons

Drawing from existing research on older coronaviruses, and a recent study, Dr. Iacobellis surmised that the role of DPP4 in such fatal outcomes is a consequential one where it hinders the body's immune response.

An important role in the inflammatory response

Dr. Iacobellis explained that the body is "overreacting with this inflammatory response" to the coronavirus. Its mediation could be partially attributed to DPP4 according to the endocrinologist.

Drawing attention to the effect of DPP4 activity in other coronavirus infections, he said: "The virus binds to the enzyme and the enzymatic activity of DPP4 overexpresses inflammatory cytokines, exaggerating the inflammatory response. Previous studies, of SARS and MERS, showed that, if you blocked DPP4 activity, there was a reduction in the inflammatory response." Such intervention may enhance the immune response against the virus, he added.

SARS-CoV-2
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A ray of hope?

While Dr. Iacobellis agreed that more data is required for the incorporation of DPP4 inhibitors in the treatment of COVID-19, there is a ray of hope. He pointed out that preliminary evidence suggests that these drugs can reduce inflammation.

According to Dr. Iacobellis, the prospective inclusion of the enzyme in the therapeutic regimen against COVID-19 warrants further study. "Starting with diabetes patients, we should be conducting randomized studies to test whether treating those with mild or moderate symptoms improves outcomes. These drugs are well tolerated and may provide therapeutic benefit," he concluded.