Research into the interaction of DPP4 and coronavirus may be a step toward a cure.
DPP4, also known as CD26, is a “serine exopeptidase expressed ubiquitously in several tissues,” one of those tissues being that of the immune cells (Strollo and Pozzilli 2). There is some research indicating that DPP4 is directly involved in the cell adhesion and virulence of SARS-CoV-2 (the virus causing COVID-19) and MERS-CoV (a similar virus that also targets similar DPP4 binding sites). Based on these facts, inhibition of DPP4 may help treat this novel coronavirus. DPP4 might also play a role in inflammation, which is associated with severe cases of COVID-19. So, inhibition of DPP4 could benefit in the treatment of this disease two-fold.
A research team at the University of Waterloo in Canada may be on the verge of developing a COVID-19 cure based on some of the above information. Preliminary studies that are not yet published are showing the use of dipeptidyl peptidase 4 (DPP4) inhibitor medications may inhibit the replication of the Coronavirus in human cells by binding directly to the virus.
Using computer software to observe the known structure of the COVID-19 virus, these researchers were able to see that known and enhanced versions of the DPP4 inhibitor structure may be able to stop the replication of the virus once it enters the body. This could potentially help cure patients with diabetes if they contract COVID-19, and eventually, an enhanced version could help cure those without diabetes as well. This research is currently limited to computer analysis, but they are working on moving to cultures and animal test subjects as quickly as possible.
These researchers have been looking into drug repurposing rather than creating a new treatment option because there are some significant benefits. Because it can take so long for a new drug to be approved and for mass production of the drug to occur, they are hoping this repurposing of DPP4 inhibitors proves a viable option to save time in this fight against the novel coronavirus. This streamlined production could also save millions in research and production since the treatment is already approved and available on the market.
Preliminary studies utilizing the above-mentioned SARS-CoV-2 and MERS-CoV viruses found they do not seem to bind to the same pocket utilized by current DPP4 inhibitors. Research on a humanized anti-CD26 monoclonal antibody, which is currently in phase one trials as an anti-tumor agent, did show significant suppression of MERS-CoV infection and did not seem to alter other immune-functions. These findings further enforce that the utilization of enhanced DPP4 inhibitors may benefit us in treating patients with COVID-19.
Researchers have just begun to scratch the surface of this medication class as a treatment option. However, based on the information we have thus far, it may at least prove a viable treatment option in some patient populations. Only time will tell as researchers continue to the next steps in this process.
As far as the treatment of patients with diabetes who have contracted COVID-19, there is no data to show if DPP4 inhibitors benefited them in recovery. Research in this area would likely be beneficial in that it would at least give us a possible option to treat these patients already at higher risk for a more severe reaction to the virus. A study could look at how patients with diabetes who are already taking a DPP4 inhibitor and contract COVID-19 compare in recovery/hospitalization time to those on other diabetic treatment options. Hopefully, this research continues to move quickly, and we see positive results soon to stop the spread of this pandemic.
- DPP4 inhibitors and enhanced versions of these medications may help cure the novel coronavirus that has caused this worldwide pandemic.
- Some research has shown that humanized CD26 (DPP4) monoclonal antibodies have stopped MERS-CoV (a similar virus to COVID-19) infections in human trials.
- Further research is needed in vivo and in vitro to tell if this medication will help stop the spread of the coronavirus once it has entered the body.
Malicdem, Darwin. “Certain Diabetes Drugs Could Hamper Spread Of Coronavirus In Diabetes Patients.” Medical Daily, May 25, 2020, https://www.medicaldaily.com/certain-diabetes-drugs-could-hamper-spread-coronavirus-diabetes-patients-novel-453209.
Strollo, Rocky, and Paolo Pozzilli. “DPP4 Inhibition: Preventing SARS‐CoV ‐2 Infection and/or Progression of COVID ‐19?” Diabetes/Metabolism Research and Reviews, 2020, doi:10.1002/dmrr.3330.
Jacob Roberts, PharmD Candidate 2021 of University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences