Biotech Updates

Researchers Discover SARS-CoV-2 Uses Heparan Sulfate to Get Inside Cells

September 16, 2020

SARS-CoV-2’s spike protein must bind both the ACE2 receptor and heparan sulfate to gain entry into human cells. Photo Source: UC San Diego Health

At the onset of COVID-19, researchers have known that SARS-CoV-2 primarily uses the molecule ACE2 to enter the cells that line the lungs and establish respiratory infections. Finding a way to block this interaction between the virus and lung cells has become the goal of many research studies. Researchers at the University of California San Diego School of Medicine have discovered that SARS-CoV-2 cannot grab onto ACE2 without a carbohydrate called heparan sulfate, which is also found on lung cell surfaces and acts as a co-receptor for viral entry.

A study led by Dr. Jeffrey Esko, Distinguished Professor of Cellular and Molecular Medicine at UC San Diego School of Medicine and co-director of the Glycobiology Research and Training Center found the role that heparan sulfate plays in health and disease. They discovered that the SARS-CoV-2 spike protein binds to heparin, a form of heparan sulfate. The team also uncovered the exact part of the SARS-CoV-2 spike protein that interacts with heparin — the receptor binding domain. When heparin is bound, the receptor binding domain opens up and increases binding to ACE2. The virus, they found, must bind both heparan sulfate on the cell surface and ACE2 in order to get inside human lung cells grown in a laboratory dish.

The team introduces a potential new approach to preventing and treating COVID-19. They showed two approaches that can reduce the ability of SARS-CoV-2 to infect human cells cultured in the lab by approximately 80 to 90 percent. The first approach involves removing heparan sulfate with enzymes, while the second one uses heparin as bait to lure and bind the coronavirus away from human cells. Heparin is already a widely used medication to prevent and treat blood clots. The team found that enzymes that remove heparan sulfate from cell surfaces prevent SARS-CoV-2 from gaining entry into cells. Likewise, treatment with heparin also blocked infection.

For more details, read the article on UC San Diego Health.

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