The coronavirus has been a cunning enemy, with new variants and subvariants evolving to evade vaccines and treatments. Researchers at Boston’s Dana-Farber Cancer Institute are working on an experimental drug that takes on one of the virus’s most damaging characteristics: its ability to mutate. and turns it on itself.
When the coronavirus binds to a receptor expression on the surface of a cell, it extracts its spike protein as prevention and triggers an infection.
The drug is designed to mimic this receptor, functioning as a killer under a disguise. When the coronavirus tries to bind to it than reality, it destroys the design of the spike protein, permanently turning off the mechanism that would stop it, according to a report published Wednesday in the journal Science Advances.
This pushes the coronavirus into a corner: If it adopts a mutation that makes it less effective at binding to the decoy drug, it will also bind less to the human cell.
The virus has discovered tactics to circumvent antibody remedies by appearing new versions of its next-generation protein. But to get around that lure, it would have to seek out and bind to another receptor, a highly unlikely option “involving super-drastic changes” in the virus, said Gordon Freeman, an immunologist at Dana-Farber and Harvard. Medical School and lead author of the study.
We are looking to combat evolution. We are looking to design this drug in such a way that it exploits evolution. James Torchia
“We’re not looking to combat evolution,” added Dr. James Torchia, a clinical researcher at Dana-Farber and Harvard Medical School and leader of the paper. “We seek to design this drug in a way that takes advantage of evolution. “
The receptor in question is called angiotensin-converting enzyme 2, or ACE2, and the drug is a decoy of the ACE2 receptor. Known at this time as DF-COV-01, it has only been tested on animals.
In those experiments, coronavirus-inflamed hamsters that didn’t receive the drug lost about 10 percent of their body weight, a measure of the severity of the infection, in the first five days. Instead, inflamed hamsters that gained the drug lost less weight. and regained weight faster. The treated hamsters also had a large viral decline in their lungs.
Several study groups have pursued a strategy of deploying decoys to disrupt infection with the SARS-CoV-2 virus, said Jun Wang, a professor of medicinal chemistry at Rutgers University. But while “the concept is simple,” he said, “Satan is in the details,” and none have yet materialized as COVID-19 therapy.
Lures cannot be packaged as pills that a patient can use at home, as they are protein and will not escape through the gastrointestinal tract. Instead, they should be given by injection or intravenously.
That said, “this document has made great progress” in advancing clients to employ such treatment, Wang said. The same is true in humans, it may mean that the experimental treatment deserves to be administered each and every day rather than daily.
From the patient’s perspective, “that’s an advantage,” he said.
But it’s still clear whether the innovations seen in hamsters will translate into humans.
“I was excited when I first read the article,” said Dr. Paul Insel, a pharmacologist at UC San Diego, who raised the option of ACE2 lures as possible COVID remedies early in the pandemic. But then he was “put off when I looked at the results. “
Although there is a lot of sublime science in this article, it is not biologically significant. Paul Insel
“Although there is a lot of sublime science in this paper,” he added, “it is not biologically significant. “
The study authors said viral load relief is modest, but noted that its effects are similar to those seen in animal studies of antibodies that have been successful in humans.
This “bodes well for its likelihood of achieving a healing effect in humans, but with the added advantages of sustained efficacy in the context of an ever-evolving virus,” they wrote.
The lure technique’s appeal increased as the coronavirus exploited its tendency to mutation. Throughout the pandemic, the virus has undergone prolific changes, in the design of the spike protein it uses to enter a mobile phone and infect its victims.
But while the virus has changed, the targeting tag it looks for in human cells, the ACE2 receptor, has not. That means the experimental drug works just as well, regardless of how the coronavirus mutates, and the study suggests that’s the case, Wang. Said.
Changes in the form of the virus increase the need for more resistant treatment. The BQ. 1 and BQ. 1. 1 subvariants, which account for nearly two-thirds of coronavirus samples recently circulating in the United States, are resistant to all lately to monoclonal antibody therapies were available. In the early stages of the pandemic, these drugs were important for unvaccinated patients and for immunocompromised patients who do not produce enough antibodies in reaction to vaccines to protect them from serious disease.
Cancer researchers have been very active in creating decoy therapies, said Dr. Timothy J. Cardozo, professor of biochemistry and molecular pharmacology at NYU Grossman School of Medicine. Uncontrolled expansion of malignant cells.
This study has produced a plethora of useful drugs, primarily for relieving inflammation in autoimmune diseases, Cardozo said. He called using virus-blocking lures “fairly new” and said studies on the ACE2 receptor make it a “promising” way to block or restrict an out-of-control infection.
This viral transmission between species. . . It could accumulate over time as the climate changes and land use continues globally. We need to be much more prepared to move forward. Dr. James Torchia
But Cardozo cautioned that since ACE2 receptors appear in many other tissues and perform signaling functions, researchers will need to remain cautious. Influencing blood pressure, a common fear with this type of protein-based medication.
The team is lately running preclinical studies to begin human trials in 2023, Torchia said.
ACE2 is the destination site for many other coronaviruses discovered in humans and especially in non-human mammalian hosts. species, Torchia said.
“This viral transmission between speciesArray. . . It can accumulate over time as climate replaces and land use continues globally,” he said. “We need to be much more prepared to move forward. “
This story made an impression on the Los Angeles Times.
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