Researchers at UC San Diego School of Medicine announced Tuesday that they have discovered a carbohydrate that the SARS-CoV-2 virus uses to bind to a lung cell molecule, which has potential implications for the treatment of patients with COVID-19.
Since January, researchers have known that the new coronavirus primarily uses a molecule known as ACE2, which is found as a gate knob on the outer surfaces of the cells lining the lungs, to enter and infect those cells. . Finding a way to block this interaction between the virus and the door knob as a means of treating infection has become the goal of many research studies.
Recently, UCSD researchers discovered that the virus cannot be caught in the ACE2 gate knob without a carbohydrate heparan sulfate, which is also found on the surfaces of lung cells.
“ACE2 is just one part of the story,” said Jeffrey Esko, professor of cellular and molecular medicine at UCSD and co-director of the Center for Research and Training in Glycobiology. “It̵7;s not the whole picture.”
Esko’s study, published in the academic journal Cell, introduces a potential new approach to preventing and treating COVID-19.
His team demonstrated two approaches that can reduce the ability of the virus to infect human cells grown in the laboratory by 80% to 90%, either by removing heparan sulfate with enzymes or by using heparin as bait for attract and bind the coronavirus away from human cells. .
Heparin, a form of heparan sulfate, is already a widely used drug to prevent and treat blood clots.
The Esko team has long studied heparan sulfate and its role in health and disease.
The team discovered that the virus binds to heparin. When heparin is bound, the virus can bind to ACE2. The researchers found that the virus must bind both heparan sulfate to the cell surface and ACE2 in order to enter human lung cells cultured in a laboratory dish.
With this viral entry mechanism established, researchers began trying to disrupt it. They found that enzymes that remove heparan sulfate from cell surfaces prevent SARS-CoV-2 from entering cells. Similarly, heparin treatment also blocks infection. Heparin treatment functioned as an antiviral at the doses currently administered to patients, even when the researchers removed the anticoagulant region from the protein, the part responsible for preventing blood clots.
Esko warned that the findings are still far from translating into a COVID-19 treatment for people. Researchers will need to test heparin and heparan sulfate inhibitors in animal models of SARS-CoV-2 infection. In a related study, scientists at UC San Diego are also exploring the role of human microbiomes, including bacteria that live in the body and in the body, in altering heparan sulfate and thus influencing susceptibility. of a person in COVID-19.
“This is one of the most exciting periods of my career: all the things we’ve learned about heparan sulfate and the resources we’ve developed over the years have come together with a wide variety of experts at various institutions that go be quick to collaborate and share ideas, ”Esko said.