The fight against COVID seems to have fallen into a ping-ponging rhythm at this point, where every step forward seems undercut by one backward. Vaccines are available, and hospitalization rates have fallen dramatically from previous peaks. But just a sliver of eligible Americans have received the most recent bivalent shot, and the specter of a new, somehow worse variant looms large in our collective psyche. Elsewhere, such as in China, we seem to be losing ground to the virus: a less effective vaccine, paired with low vaccination rates, limited natural immunity, and discontent over a national Zero-COVID policy, may spell disaster in the coming weeks. But amid this impasse, scientists may have found a drug that will decisively shift the battle back toward humanity’s side. And the best part is, people have already been prescribed this drug for over 30 years.
Though they can be highly effective, our current methods of preventing and treating COVID-19 infections all suffer from a fatal flaw, said Teresa Brevini, a U.K. biologist who recently completed her PhD at Cambridge University.
“Vaccines, monoclonal antibodies, and antivirals all act on the virus, and unfortunately, as we’ve seen, this virus is quite smart and it can mutate,” Brevini told The Daily Beast. She is the first author of a new study into ursodeoxycholic acid, or UDCA, to prevent COVID. Crucially, instead of acting on the virus, UDCA modifies human cells to block the virus from infecting them. “If we just shut the door on the virus, it really cannot do anything,” Brevini said.
Brevini and her colleagues’ research was published in the journal Nature on Monday.
UDCA “shuts 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 by a twist of fate, it also makes for the perfect docking station for the SARS-CoV-2 spike protein. When the virus infects the cells in a person’s respiratory tract, it uses ACE2 receptors like doorways.
“If we just shut the door on the virus, it really cannot do anything.”
— Teresa Brevini
In the early months of the pandemic, Brevini and her 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, ‘Hang on—ACE2, the door 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 that the next scientific hypothesis came logically to her and her team: “If we have a way to increase how much receptor is present on the cell—so how susceptible the cells can be to the virus—maybe we can use the same mechanism to reduce the amount of the receptor.”
She and her co-authors started pulling on this thread, testing UDCA on cultured clusters of gallbladder, lung, and intestinal cells and determining that it lowered ACE2 levels in all three cell types. Subsequently infecting these masses of cells with SARS-CoV-2 significantly decreased the amount of viral genetic material compared to clumps that had not been given the drug. They repeated this experiment in mice and hamsters before moving onto a pair of human lungs on a mechanical ventilator. This part, Brevini said, was “like Frankenstein.”
“You see the lungs outside the body, and there is a ventilator, and you see them inflating and deflating. 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 in the treated lung had cells with fewer ACE2 receptors than in the untreated lung, and these regions were then less susceptible to viral infection.
Most experimental therapies take years of clinical study before they ever make it into a living human, but UDCA is already widely…
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