Home > Research Diseases > Coronavirus
Centenary Institute - Medical Research
Centenary Institute - Medical Research

Human enzyme DPP4 does not enable COVID-19 infection

Research from the Centenary Institute has found that the human enzyme dipeptidyl peptidase (DPP4) does not bind to the spike protein of the SARS-CoV-2 virus and so cannot enable COVID-19 infection in our bodies.

DPP4, which is known to be the key receptor for the MERS-coronavirus (Middle East respiratory syndrome), had been identified as a potential binding target of the SARS-CoV-2 spike protein. The spike protein forms the spikes of the ‘crown’ after which coronaviruses are named. If DPP4 had been able to bind, it would have suggested an alternate port of entry for SARS-CoV-2 into human cells, thus exacerbating COVID-19.

“We already know that SARS-CoV-2 cell entry depends on the interaction between the virus’ spike and the human enzyme ACE2. We needed to find out if DPP4 was also acting as a gateway for COVID-19,” said senior author on the paper, Professor Mark Gorrell, Head of the Liver Enzymes in Metabolism and Inflammation Program at the Centenary Institute.

“Our findings however put to rest the suggestion that DPP4 could be a co-receptor or alternate receptor for SARS-CoV-2 entry. There was no binding detected between the two molecules in our study and so we can be reassured that ACE2 is the sole method for SARS infection.”

The publication, which is in pre-print, is accessible online: A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2.

Further Information on the Centenary Institute’s coronavirus activity can be found here.

COVID-19 research targets human enzymes

Centenary Institute researchers have examined the critical role of human enzymes and the coronavirus in a newly published scientific review article that explores potential strategies for COVID-19 disease treatment and management.

The review article published in the prestigious ‘Journal of Diabetes’, seeks to explain how the human enzyme dipeptidyl peptidase (DPP4), which is a driver of diabetes severity, could be exacerbating COVID-19.

“COVID-19 is more severe in people who have type 2 diabetes, obesity and related chronic diseases,” says Professor Mark Gorrell (Head of the Centenary Institute Liver Enzymes in Metabolism and Inflammation Program) and senior author of the review article.

“We also see more DPP4 made in people with diabetes, obesity and related chronic diseases. Drugs that target DPP4 enzyme activity are regularly taken by many people for type 2 diabetes. Such drugs may have immune system and cardioprotective effects that could be beneficial in COVID-19 cases,” he says.

The review article notes that DPP4, which is known to be the key receptor for the MERS-coronavirus (Middle East respiratory syndrome) might also be an additional or alternate port of entry for SARS-CoV-2 into human cells.

“COVID-19 is caused by the SARS-CoV-2 coronavirus, which is similar to SARS-CoV and MERS-CoV. Each of these viruses attach to and enter human cells by binding to specific human enzymes,” says Professor Gorrell.

“Recent research suggests that SARS-CoV-2 can bind to both DPP4 and the ACE2 enzyme and so have two ways to infect our lungs and gut. Once we fully understand this process, we may be able to develop a drug that can help disrupt this viral activity,” he says.

Professor Gorrell, an expert in human proteases (enzymes that break down proteins) has recently launched a new research program in response to the growing COVID-19 pandemic.

“TMPRSS2 (Transmembrane protease, serine 2) is essential for SARS-CoV and SARS-CoV-2 infection. This protease activates the viral protein on the coronavirus necessary for virus cell entry at the start of viral infection in the human body,” he says.

“We are looking to develop a selective TMPRSS2 inhibitor that is both effective and very safe using our expertise and a unique drug screening approach. The successful development of such an inhibitor could be utilised as a novel therapy for both past and current, and possibly future, SARS-CoV coronaviruses.”

“I’m optimistic that our research will contribute meaningfully to the global COVID-19 health response,” he says.

Read the full media release here.

Further Information on the Centenary Institute’s coronavirus activity can be found here.