Home Health Pocket feature shared by deadly coronaviruses could lead to pan-coronavirus antiviral treatment

Pocket feature shared by deadly coronaviruses could lead to pan-coronavirus antiviral treatment

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Spike glycoprotein structure of SARS-CoV, the coronavirus that caused the 2002 outbreak. When linoleic acid binds, the structure is fixed in a non-infectious form. Cryo-EM densities calculated by cloud computing are shown (left) along with the protein structure (middle). Linoleic acid molecules are colored orange. A close-up of the pocket (boxed) stored in all deadly coronaviruses is shown.Credit: Christine Schaffitzel and Christine Toelzer, University of Bristol

Scientists have discovered why some coronaviruses are more likely to cause severe illness, which until now has remained a mystery. scientific progress Today (November 23), their findings pave the way for the development of a pan-coronavirus treatment to defeat all coronaviruses, from the 2002 SARS-CoV outbreak to the current variant of SARS-CoV-2, Omicron. said it could lead to that may appear in the future.

In this new study, an international team led by Professor Christiane Schaffitzel of Bristol has scrutinized the spike glycoprotein that adorns all coronaviruses. They reveal that the tailor-made pocket function of the SARS-CoV-2 spike protein, first discovered in 2020, is present in all deadly coronaviruses, including MERS and Omicron. In addition, the pocket function is absent in coronaviruses, which cause mild infections with cold-like symptoms.

The team found that the pocket that binds small molecules linoleic acid— An essential fatty acid that is essential for many cell functions, including inflammation, and maintains cell membranes in the lungs so they can breathe properly — Currently available to treat all deadly coronaviruses, while they vulnerable to linoleic acid-based therapies.We are targeting this pocket.

Caused by SARS-CoV-2, COVID-19 is the third coronavirus outbreak after SARS-CoV in 2002 and MERS-CoV in 2012. The much more contagious SARS-CoV-2 continues to infect people and damage communities and economies around the world. New variants of interest continue to emerge to evade vaccination and immune responses.

“Previous research has identified the presence of linoleic acid, a small molecule buried in a tailor-made pocket within the SARS-Cov-2 glycoprotein, known as the ‘spike protein,'” said Professor Schaffitzel of the Bristol School of Biochemistry. Did. , which binds to the cell surface in humans, allowing the virus to enter the cell and begin replicating, causing widespread damage.

“It has been shown that binding linoleic acid to the pocket can stop the virus from becoming infective, suggesting an antiviral treatment. It was in the original Wuhan strain that caused the pandemic. It has since been , a full range of dangerous SARS-CoV-2 variants has emerged, including the now dominant Omicron Mutant I’m curious. We’ve scoured every new variant of concern and asked if the pocket functionality still exists. “

Omicron has undergone many mutations, allowing it to evade the immune protection provided by vaccination and antibody therapy that lags behind this rapidly evolving virus. Interestingly, while everything else may have changed, the researchers found that the omicron pocket remained virtually unchanged.

Christine Toelzer, Research Associate in the Department of Biochemistry and lead author of the study, added: A previous outbreak many years ago also contained this linoleic acid-binding pocket function. ”

The team applied high-resolution electron cryomicroscopy, state-of-the-art computational approaches, and cloud computing. Their results showed that SARS-CoV and MERS-CoV also have pockets and can bind their ligand, linoleic acid, by virtually identical mechanisms.

Professor Schaffitzer said, “In our current study, from the first SARS-CoV outbreak 20 years ago, Omicron today. We have previously shown that binding of linoleic acid to this pocket induces a locked spike and abolishes viral infectivity.It also shows that linoleic acid supplementation is suppressed viral replication intracellular. Future variants include pocket, which can be exploited to defeat viruses. ”

For more information:
Christine Toelzer et al, The Free Fatty Acid-Binding Pocket is a Conserved Hallmark in Pathogenic β-Coronavirus Spike Proteins from SARS-CoV to Omicron, scientific progress (2022). DOI: 10.1126/sciadv.adc9179. www.science.org/doi/10.1126/sciadv.adc9179

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Bristol University

Quote: Pocket Capabilities Shared by Deadly Coronavirus May Lead to Pan-Coronavirus Antiviral Treatments (23 November 2022) November 23, 2022 at https://phys.org/news Retrieved from /2022-11-pocket-feature-deadly-coronaviruses-pan- coronaviruses.html

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