London: Scientists have discovered that a custom-made pocket within the SARS-CoV-2 spike protein, which can attach itself to the human cell surface, has some consequences. coronaviruses causes severe illness.
An international research team has studied the spike glycoproteins that adorn all coronaviruses. During the study, the researchers found that although personalized pocket is present in all deadly coronaviruses, including MERS and Omicron, the feature is absent in variants that cause mild infection with cold-like symptoms.
Researchers of the University of Bristol-led study said their findings could lead to the development of a treatment that would defeat all coronaviruses, from the 2002 SARS-CoV outbreak to Omicron, the current variant of SARS-CoV-2. variants that may arise in the future.
The findings of the study were published in a journal called ‘Science Advances’.
The team said their findings suggest that the pocket binds to a small molecule, linoleic acid; it is an essential fatty acid essential for many cellular functions, including inflammation and protecting cell membranes in the lungs so humans can breathe properly.
This pocket can now be used to treat all deadly coronaviruses, while also making them vulnerable to a linoleic acid-based therapy that targets this pocket.
COVID-19, caused by SARS-CoV-2, is the third deadliest coronavirus outbreak after SARS-CoV in 2002 and MERS-CoV in 2012.
The much more contagious SARS-CoV-2 continues to infect people worldwide and wreak havoc on communities and economies, with successive new variants of concern and Omicron evade the vaccination and immune response.
“In our previous work, we identified the presence of a small molecule, linoleic acid, embedded in a specially crafted pocket within the SARS-CoV-2 glycoprotein known as the ‘Spike protein’ that binds to the human cell surface. and causing widespread damage, allowing it to begin to proliferate,” he said.
“We showed that the pocket-binding linoleic acid can stop virus transmission, suggesting it is an anti-viral treatment. It was in the original Wuhan strain that started the pandemic.
«Since then, a number of dangerous variants of SARS-CoV-2 have emerged, including Omicron, which is now of concern. We examined each new strain of concern and asked if pocket function was still present,» said Schaffitzel.
Omicron has undergone many mutations that allow it to evade the immune protection offered by vaccination or antibody treatments that lagged behind this rapidly evolving virus. According to the study, while everything else had changed, the researchers found that the pocket remained virtually unchanged in the Omicron as well.
«When we realized that the pocket we discovered had not changed, we looked back and asked whether SARS-CoV and MERS-CoV, the other two deadly coronaviruses that caused previous outbreaks years ago, also contained this linoleic acid-binding pocket feature,» said Christine Toelzer. , lead author of the study.
The team applied high-resolution electron cryo-microscopy, cutting-edge computational approaches, and cloud computing.
Their results showed that SARS-CoV and MERS-CoV also have pockets and can bind the ligand, linoleic acid, by almost the same mechanism.
«In our current study, we provide evidence that the pocket remains the same across all deadly coronaviruses, from the first SARS-CoV outbreak 20 years ago to the Omicron today,» said Schaffitzel.
“We have previously shown that linoleic acid attached to this pocket creates a locked spike that abolishes viral infectivity. We now also show that linoleic acid supplementation suppresses virus replication within cells.
«We anticipate that future variants will also include the pocket that we can use to defeat the virus,» said Schaffitzel.
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