New discovery may change how dexamethasone is prescribed for some COVID-19 patients

DOE/ARGONNE NATIONAL LABORATORY

Research has shown that dexamethasone, a widely available steroid, can significantly reduce the chance of death from COVID-19. However, because of the way dexamethasone is transmitted throughout the body, it may be less effective in patients with diabetes, according to new research performed at the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Argonne National Laboratory.

A research team led by scientists at the University of Virginia studied the way a blood protein, called serum albumin, picks up and transports dexamethasone throughout the body. The team used powerful X-rays from the APS to get a full picture of the structure of serum albumin combined with dexamethasone. Their work was published in the Journal of the International Union of Crystallography.

Low levels of albumin may already make it more difficult for some patients to get the benefits of dexamethasone. This research shows that patients with diabetes may experience the same difficulty, since high blood sugar changes the way albumin binds with dexamethasone. These findings, researchers say, may lead to physicians rethinking how they prescribe the drug for certain patients.

The X-ray macromolecular crystallography work was performed at Life Sciences Cooperative Access Team (LS-CAT) beamline 21-ID-F at the APS. The research team made use of remote access technology to control the APS beam without visiting the site.

“Gaining new insight into the mechanisms of this drug will help doctors design more effective treatments,” said Argonne’s Bob Fischetti, life sciences advisor to the APS director. “Since the start of this pandemic, the APS has been a powerful tool for gaining insights into the virus itself, and into methods for combating it.”

This research is the latest of many contributions the APS has made to the battle against COVID-19. Since January the APS has devoted more than 8,000 hours of experimental time across multiple X-ray beamlines to research on the SARS-CoV-2 virus. As of October 2020, more than 70 groups of researchers have used the APS to learn more about the virus, and lay the groundwork for treatments and vaccines.