UC San Diego School of Medicine researchers announced Tuesday that they have discovered a carbohydrate that SARS-CoV-2 virus uses to attach to a cellular molecule in the lungs, which has potential implications for the treatment of COVID-19 patients.
Since January, researchers have known that the new coronavirus primarily uses a molecule known as ACE2 – which sits as a door handle on the outer surfaces of the cells that line the lungs – to enter and infect those cells. Finding a way to lock out the interaction between virus and door handle as a means of treating the infection has become the goal of many research studies.
UCSD researchers recently discovered that the virus cannot seize the ACE2 door handle without a carbohydrate-heparan sulfate, which is also found on lung cell surfaces.
“ACE2 is only part of the story,”
The Esko study, published in the academic journal Cell, introduces a potential new approach to the prevention and treatment of COVID-19.
His team demonstrated two approaches that can reduce the virus’ ability to infect human cells grown in the laboratory by approx. 80% to 90%, either by removing heparan sulfate with enzymes or using heparin as bait to lure and bind coronavirus away from human cells.
Heparin, a form of heparan sulfate, is already a widely used drug for the prevention and treatment of blood clots.
Esko’s team has long studied heparan sulfate and the role it plays in health and disease.
The team discovered that the virus binds to heparin. Once heparin is bound, the virus is able to bind to ACE2. The virus, the researchers found, must bind both heparan sulfate on the cell surface and ACE2 to enter human lung cells grown in a laboratory dish.
With this viral entry mechanism established, the researchers next time went on to try to disrupt it. They found that enzymes that remove heparan sulfate from cell surfaces prevent SARS-CoV-2 from entering cells. Likewise, treatment with heparin also blocked infection. The heparin treatment acted as an antiviral dose that is currently given to patients even when the researchers removed the anticoagulant region of the protein – the part responsible for preventing blood clots.
Esko warned that the results are still far from translating into a COVID-19 treatment for humans. Researchers will need to test heparin and heparan sulfate inhibitors in animal models of SARS-CoV-2 infection. In a related study, researchers from UC San Diego are also investigating the role that human microbiomes, including bacteria that live in and on the body, play in altering heparan sulfate and thus affecting a person’s sensitivity to COVID-19.
“This is one of the most exciting periods of my career – all the things we’ve learned about heparan sulphate and the resources we’ve developed over the years have come together with a number of experts across several institutions who were quick to collaborate and share ideas, ”said Esko.