UC San Diego research offers potential new treatments for COVID by revealing how virus enters cells

Study shows virus uses a key sugar to hijack cells
Posted at 5:34 PM, Oct 06, 2020

SAN DIEGO (KGTV) — The National Institutes of Health highlighted research Tuesday out of UC San Diego that could unlock a new way to treat COVID-19.

The research reveals new insight into how the coronavirus hijacks cells, and how doctors might be able to set traps or decoys to combat the virus. The findings were published in the journal Cell last month.

“It does open up another avenue for a potential treatment,” said UC San Diego distinguished professor Dr. Jeffrey Esko. “It’s not a cure. It would be something that would tamp down infection potentially.”

Since January, scientists around the world have understood that SARS-Co-V2, the official name of the new coronavirus, enters cells by latching onto a specific receptor on the cell’s surface, called ACE2.

The UCSD team, led by Dr. Esko and visiting scholar Dr. Thomas Clausen, discovered that this entry mechanism is actually a two-step process, and the virus must also attach to a long chain of sugars called heparan sulfate.

“We’ve shown this is fundamental to the infectious mechanism, so it needs to be part of every study from now on,” said Clausen.

All cells are coated with a complex layer of sugars, or carbohydrates, called glycans. Heparan sulfate is one type of glycan that is known to play a key role in the infection process in several viruses, including herpes and other coronaviruses.

It’s a complicated process to picture so the researchers offer an analogy: imagine a bird, soaring over trees, hunting a worm on the forest floor. The bird is the coronavirus and the trees are the thick layer of glycans that coat the surface of the cell.

To reach the worm, which in this case is the receptor ACE2, the bird must navigate its way through the trees, specifically through heparan sulfate.

The UCSD found that by removing the heparan sulfate trees with an enzyme, they were able to prevent the virus from infecting cells. In laboratory testing, they also found a second technique worked to foil the virus: introducing more trees as bait.

The team found that heparin, an FDA-approved drug that is similar in structure to heparan sulfate, successfully acted as decoy. Heparin is a widely used drug designed to treat blood clots. Since blood clots and strokes are common complications with COVID-19, many doctors already administer heparin to patients.

The UCSD team demonstrated that the two approaches can block infection in lab-grown cells about 80 to 90 percent of the time.

“Certainly in the laboratory you can demonstrate that it works, but to deploy it and use it as a therapeutic has not been demonstrated,” Esko said.

The NIH noted that more studies are planned to explore whether heparin, heparan sulfate, or drugs that target heparan sulfate might yield a viable COVID-19 treatment.

Dr. Esko said he’s already been in talks with companies that plan to use their study as a rationale for a clinical trial.

“It is very humbling when you realize we’re working on a pandemic right now, and maybe what we’ve done can contribute to a treatment for the disease,” he said.