A new discovery of how the frame carries dexamethasone, a drug that can increase the chances of survival in patients with severe COVID-19, suggests that diabetes and other points would possibly reduce its potentially important efficacy.
Based on their findings, researchers say doctors may want to reconsider how they administer the drug to certain patient teams.
The team of scientists, founded at the University of Virginia School of Medicine, the University of South Carolina and Poland, has decided how a protein in our blood called serum albumin captures dexamethasone and takes it where it’s needed.
Low serum albumin levels are already a major threat to severe COVID-19, as is diabetes.
New studies suggest that diabetes or low albumin levels may make it difficult for patients to discharge the benefits of dexamethasone, a corticosteroid that soothes the overactive immune reaction that can lead to death in severe cases of COVID-19.
Diabetes is linked to the upper level of blood sugar, causing a replacement in albumin that can adjust the binding site of dexamethasone. Other drugs would possibly also compete with dexamethasone for a limited area in serum albumin reserves. Albumin’s carrying capacity is also naturally reduced when there is a low point of albumin in the blood.
At this stage, we do not have a more available remedy than dexamethasone for severe cases of COVID-19, but, like COVID-19 itself, its efficacy is somewhat unpredictable. To give a complete picture, this study was conducted in collaboration with structural biologists, computer scientists and clinicians. Therefore, each of the authors of this article had to think outdoors to mix medical knowledge with the effects of structural biology in order to recommend imaginable adjustments to the remedy that could potentially save more human lives. . “
Researcher Ivan Shabalin, PhD, first in a new paper describing the results, added, “Working on this interdisciplinary team and seeing how our fundamental science studies can save lives in the existing pandemic seemed incredibly rewarding to us. “
For the first time, Minor and her colleagues demonstrated precisely how serum albumin joins dexamethasone so that the drug can be distributed in our bodies.
Serum albumin joins dexamethasone in the same way that it joins the hormone testosterone, suggesting that the two may compete with the other, the researchers report. More men die from COVID-19 than women, and low testosterone levels have already been linked to worse results.
The study authors hypothesized that maximum levels of dexamethasone can only send testosterone by competing for the same drug site in albumin.
Serum albumin also uses the same binding base to recover several non-unusual nonsteroidal anti-inflammatory drugs, so doctors may want the future of the festival to make a decision on COVID-19 remedy plans, studies suggest.
However, it is as undeniable as expanding the dose of dexamethasone for patients with diabetes or low serum albumin levels. Too much dexamethasone can be destructive or have unwanted side effects.
More studies are needed to determine the most productive dose in various patient populations, especially for others with diabetes or low albumin levels, according to researchers.
To better perceive the role of serum albumin in COVID-19, researchers analyzed the knowledge of 373 patients at a hospital in Wuhan, China, who treated many severe cases of the disease. Scientists found that deceased patients had lower grades of albumin than those who survived.
Those who died also had high blood sugar levels, which is consistent with researchers’ conclusion that the upper blood sugar level may be just the ability of serum albumin to carry their load.
“To provide an immediate reaction to emerging demanding biomedical situations and threats like COVID-19, we want to analyze medical knowledge in the context of other in vitro and in vivo outcomes,” Minor said. “Five years ago, I wrote in Expert Opinion at Drug Discovery that, ‘The use of recent advances in biochemical, spectroscopic and bioinformatics strategies can revolutionize drug discovery, but only when that knowledge is combined and analyzed with effective knowledge control systems. “This assessment remains valid and obviously little progress has been made, as it is not misidentified as a major challenge for biomedical sciences. “
“Until a vaccine or new drugs become widely available, we want to make the most productive use of drugs we know can fight COVID-19,” added team member Dariusz Brzezinski, PhD.
University of Virginia Health System
Shabalin, I. G. , et al. (2020) Molecular determinants of vascular transport of dexamethasone in COVID-19 IUCrJ. doi. org/10. 1107/S2052252520012944.
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