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Coronavirus' ability to bind to human cell surface cause severe disease: Report

Scientists find tailor-made pocket feature shared by coronaviruses causing severe disease (AFP)Premium
Scientists find tailor-made pocket feature shared by coronaviruses causing severe disease (AFP)

Scientists have discovered that a tailor-made pocket within the SARS-CoV-2 spike protein, which is capable of binding itself to the human cell surface, is what results in some coronaviruses causing severe disease

Researchers have found that the ability of the SARS-CoV-2 spike protein to bind itself to the surface of human cells is what causes some coronaviruses to cause severe disease.

The spike glycoproteins that all coronaviruses have were examined by an international team of researchers. Researchers discovered during the study that while the feature was present in all lethal coronaviruses, including MERS and Omicron, it was absent in variations that cause mild infection with cold-like symptoms.

The 2002 SARS-CoV outbreak, the current SARS-CoV-2 variant Omicron, and potentially dangerous future variants could all be eliminated with a treatment, according to the study's researchers, who were led by the University of Bristol.

The study's results have been released in the journal "Science Advances."

The team's research indicated that a small molecule called linoleic acid, an essential fatty acid required for many cellular processes, including inflammation and maintaining lung cell membranes for proper breathing in humans, was bound to the pocket.

This pocket could now be used to treat every lethal coronavirus while also making them susceptible to a linoleic acid-based treatment that targets this pocket.

After the SARS-CoV outbreak in 2002 and the MERS-CoV outbreak in 2012, COVID-19, which was brought on by SARS-CoV-2, is the third deadliest coronavirus outbreak.

With successively new variants of concern emerging and Omicron eluding immunisation and immune response, the much more contagious SARS-CoV-2 continues to spread throughout the world, infecting people and destroying communities and economies.

"In our earlier work, we identified the presence of a small molecule, linoleic acid, buried in a tailor-made pocket within the SARS-CoV-2 glycoprotein, known as the 'Spike protein', which binds to the human cell surface, allowing the virus to penetrate the cells and start replicating, causing widespread damage," explained Christiane Schaffitzel from School of Biochemistry, University of Bristol.

"We showed that binding linoleic acid in the pocket could stop virus infectivity, suggesting an anti-viral treatment. This was in the original Wuhan strain that started the pandemic. Since then, a whole range of dangerous SARS-CoV-2 variants have emerged, including Omicron, the currently dominating variant of concern. We scrutinised every new variant of concern and asked whether the pocket function is still present," Schaffitzel added.

Omicron has undergone numerous mutations, making it immune protection provided by vaccination or antibody treatments that lag behind this rapidly evolving virus. The pocket, which is also in Omicron, was virtually unchanged, the researchers discovered, even though everything else may have changed.

"When we realised that the pocket we had discovered remained unchanged, we looked back and asked whether SARS-CoV and MERS-CoV, two other deadly coronaviruses causing previous outbreaks years ago, also contained this linoleic acid binding pocket feature," said Christine Toelzer, lead author of the study.

High-resolution electron cryo-microscopy, cutting-edge computational techniques, and cloud computing were all used by the team. Their findings demonstrated that SARS-CoV and MERS-CoV both possessed the pocket and had a nearly identical mechanism for binding the ligand, linoleic acid.

"In our current study, we provide evidence that the pocket remained the same in all deadly coronaviruses, from the first SARS-CoV outbreak 20 years ago to Omicron today," said Schaffitzel.

"We have shown previously that linoleic acid binding to this pocket induces a locked spike, abrogating viral infectivity. We also show now that linoleic acid supplementation suppresses virus replication inside cells. We anticipate that future variants will also contain the pocket, which we can exploit to defeat the virus," Schaffitzel concluded.

(With inputs from PTI)

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