Los Angeles: Scientists have identified a key carbohydrate molecule, called heparan sulphate, which the novel coronavirus uses to infect human cells, an advance that may provide a potential new approach for preventing and treating COVID-19. The molecule ACE2 sits like a doorknob on the outer surfaces of the cells that line the lungs, and researchers know that SARS-CoV-2 virus primarily uses it to enter these cells and establish respiratory infections. The study, published in the journal Cell, found that SARS-CoV-2 can''t grab onto ACE2 without heparan sulphate, which is also found on lung cell surfaces and acts as a co-receptor for viral entry. "ACE2 is only part of the story.
It isn''t the whole picture," said Jeffrey Esko, a professor at the University of California San Diego School of Medicine in the US. The team demonstrated two approaches that can reduce the ability of SARS-CoV-2 to infect human cells cultured in the lab by approximately 80 to 90 per cent. The first approach works by removing heparan sulphate with enzymes, and the second uses heparin as bait to lure and bind the coronavirus away from human cells, according to the researchers. Heparin, a form of heparan sulphate, is already a widely used medication to prevent and treat blood clots, suggesting that an approved drug might be repurposed to reduce virus infection, they said.
The team uncovered the exact part of the SARS-CoV-2 spike protein that interacts with heparin -- the receptor binding domain. The researchers found that when heparin is bound, the receptor binding domain opens up and increases binding to ACE2. The virus must bind both heparan sulphate on the cell surface and ACE2 in order to get inside human lung cells grown in a laboratory dish, they said. With this viral entry mechanism established, the researchers next set about trying to disrupt it. They found that enzymes that remove heparin sulphate from cell surfaces prevent SARS-CoV-2 from gaining entry into cells. Similarly, treatment with heparin also blocked infection, according to the researchers.
The heparin treatment worked as an anti-viral at doses currently given to patients, even when the researchers removed the anticoagulant region of the protein -- the part responsible for preventing blood clots, they said.
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