Our next best COVID drug has been hidden in plain sight


The fight against COVID appears to have fallen into a ping-pong pace at this point, where every step forward seems thwarted by one backward. Vaccines are available and hospitalization rates have dropped dramatically from previous peaks. But only a sliver of eligible Americans has received the most recent dual blow, and the specter of a new, somewhat worse variant hangs in our collective psyche. Elsewhere, like in China, we appear to be losing ground to the virus: A less effective vaccine, coupled with low vaccination rates, limited natural immunity, and discontent with a national zero-COVID policy could spell disaster in the coming weeks. But amid this impasse, scientists may have found a drug that will decisively bring the battle back to humanity’s side. And the best part is, people have already been prescribed this drug for over 30 years.

While they may be highly effective, our current methods of preventing and treating COVID-19 infections all suffer from a fatal flaw, said Teresa Brevini, a British biologist who recently completed her PhD. at the University of Cambridge.

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“Vaccines, monoclonal antibodies and antivirals all act on the virus and unfortunately, as we have seen, this virus is quite intelligent and can mutate,” Brevini told The Daily Beast. She is the first author of a new study using ursodeoxycholic acid, or UDCA, to prevent COVID. Basically, instead of acting on the virus, UDCA modifies human cells to prevent the virus from infecting them. “If we just close the door on the virus, it can’t really do anything,” Brevini said.

The research by Brevini and his colleagues has been published in the journal Nature on Monday.

UDCA “closes the door” on COVID by decreasing the amount of a receptor called ACE2 on the surface of cells. ACE2 normally controls blood pressure and limits organ damage, but in a twist of fate, it also forms the perfect docking station for the SARS-CoV-2 spike protein. When the virus infects cells in a person’s respiratory tract, it uses ACE2 receptors as gates.

In the early months of the pandemic, Brevini and his lab were working remotely during lockdown when they noticed a quirk in some of their liver cells.

“We were all at home, checking some of our data on the computer, and we said, ‘Wait, ACE2, the gateway that the virus uses, is expressed in our cells,'” Brevini said. Not only that, the researchers had unintentionally increased the number of ACE2 receptors in some of their liver cells. Brevini said the next scientific hypothesis came logically to her and her team: ‘If we have a way to increase the amount of receptors present on the cell, so how susceptible cells can be to the virus, perhaps we can use the same mechanism to reduce the amount of the receptor.”

She and her coauthors began pulling on this thread, testing UDCA on cultured groups of cells from the gallbladder, lung and intestines and determining that it lowered ACE2 levels in all three cell types. Subsequently, the infection of these cell masses with SARS-CoV-2 significantly reduced the amount of viral genetic material compared to the clumps that had not been given the drug. They repeated this experiment on mice and hamsters before switching to a pair of human lungs on a mechanical ventilator. This part, Brevini said, was “like Frankenstein”.

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“You see the lungs outside the body, and there’s a ventilator, and you see them inflate and deflate. My mind was blown seeing this experiment,” she said.

The researchers split the lungs in two and gave one lung UDCA while using the other as a control. After six hours, three areas of the treated lung had cells with fewer ACE2 receptors than untreated lung, and these regions were therefore less susceptible to viral infection.

Most experimental therapies require years of clinical trials before they can make it into a living human, but UDCA is already widely prescribed for the treatment of cholestatic liver disease. By comparing COVID-19 infection data from patients with chronic liver disease who took and didn’t take UDCA, Brevini and his colleagues were able to analyze the results of a natural experiment. They found that UDCA patients had a 46% reduced chance of contracting COVID-19; when they caught the virus, they were less likely to show moderate, severe, or critical forms of the disease than patients with liver disease who weren’t taking the drug.

Eventually, eight healthy volunteers agreed to take UDCA in pill form for five days. The researchers measured ACE2 levels in the nose with daily nasopharyngeal swabs, finding reduced levels of the receptors even within a few days. Brevini said this finding gives her hope that the pill could one day be used as a way to reduce the risk of getting an infection, with or without exposure.

“Let’s say you have lunch with your colleague one day, and then they text you the next day saying, ‘I’m so sorry, I’ve developed COVID,'” Brevini said. “If you’ve gotten the vaccine, you’re protected in that respect, but is there anything else you can do? We think you might want to take it preventatively to reduce the chances of this particular virus infecting your cells.

“It’s remarkable that a drug that’s safe and available” could be able to prevent COVID-19 infections, Stuart Lipton, a molecular medicine researcher at the Scripps Research Institute, told The Daily Beast in an email. been involved in the study. “The drug certainly deserves further testing” in a forward-looking, randomized human clinical trial, he added.

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Even so, Lipton cautioned that UDCA can have undesirable side effects on blood pressure and kidney function in humans, which can occur when the number of ACE2 receptors on a cell decreases.

“I am concerned that widespread use of the drug could reveal serious and unwanted side effects, especially in elderly and vulnerable populations who are most in need of drug treatment,” he said.

Other research groups are working on ways to downregulate ACE2 receptors only in cells vulnerable to SARS-CoV-2 infection, in the respiratory tract and lungs. Lipton conducted a study which was published in Chemical biology of nature in September and found that a targeted method of blocking ACE2 reduced the virus’s ability to infect human and hamster cells.

What these methods have in common is a promising tactic for fighting this virus that we’ve always had in our arsenal: slamming the doors on our cells and preventing infection in the first place.

Read more at The Daily Beast.

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