A pocket feature shared by deadly coronaviruses may lead to a pan-antiviral cure – ScienceDaily


Scientists have discovered why some coronaviruses may cause serious disease, which has remained a mystery until now. The University of Bristol-led study researchers published in Science advances today [23 November]He says their findings could lead to the development of a universal coronavirus treatment to defeat all coronaviruses — from the 2002 SARS outbreak to Omicron, the current variant of SARS-CoV-2, as well as dangerous variants that may emerge in the future.

In this new study, an international team led by Bristol Professor Christian ChaffetzlAnd the Examination of the elevated glycoproteins that decorate all coronaviruses. They revealed that a specially designed pocket feature in the SARS-CoV-2 spike protein, first Discover In 2020, it is present in all deadly coronaviruses, including MERS and Omicron. In stark contrast, there is no sinus feature in coronaviruses that cause mild infections with cold-like symptoms.

The team says their findings indicate that sinus, which binds a small molecule, linoleic acid — an essential fatty acid that is indispensable for many cellular functions including inflammation and maintaining cell membranes in the lungs so we can breathe properly — can now exploiting it to treat all deadly coronaviruses, simultaneously making them vulnerable to a linoleic acid-based treatment that targets this sinus.

COVID-19, caused by SARS-CoV-2, is the third deadliest coronavirus outbreak after SARS in 2002 and MERS-CoV in 2012. The most infectious virus, SARS-CoV-2, continues to infect people and harm societies and economies around the world. Over the world, with the emergence of new worrisome variants in succession, the Omicron and the evasion of vaccination and the immune response.

Professor Chaffetzl of Bristol School of BiochemistryHe explained: “In our previous work, we identified the presence of a small molecule, linoleic acid, buried in a specially designed pocket within the SARS-Cov-2 glycoprotein, known as the ‘spike protein’, which binds to the human cell surface, allowing the virus to penetrate cells and begin to infect.” Reproducing, causing massive damage.

We showed that binding of linoleic acid to the pocket could stop virus infection, suggesting an antiviral therapy. This was in the original Wuhan dynasty that started the epidemic. Since then, a whole host of dangerous variants of SARS-CoV-2 have emerged, including Omicron, the currently dominant variant of anxiety. We checked each new variable of concern and asked if the sine function was still present.”

Omicron has undergone many mutations, enabling it to escape the immune protection afforded by vaccination or antibody therapies that lag behind this rapidly evolving virus. Interestingly, while everything else changed, the researchers found that the pocket remained almost unchanged, also in Omicron.

Christine Tolzera research associate in the School of Biochemistry and the study’s lead author, added: “When we realized the pocket we had detected hadn’t changed, we looked back and asked if SARS-CoV and MERS-CoV, two other deadly viruses that previously caused outbreaks years ago, contained it.” also on the pocket feature associated with linoleic acid.”

The team applied high-resolution electron microscopy, advanced computational methods and cloud computing. Their findings showed that SARS-CoV and MERS-CoV also possess the pocket, and can bind the ligand linoleic acid by an almost identical mechanism.

Professor Schaffetzel concluded: “In our current study, we provide evidence that the pocket has remained the same in all killer coronaviruses, from the first outbreak of SARS-CoV 20 years ago to Omicron today. We have previously shown that binding of linoleic acid to this pocket leads to a closed spike “.

Hello TherapeuticsProfessor Schaffetzel, who recently co-founded the University of Bristol, is using these findings to develop antivirals for pocket-binding pan-coronaviruses.

The team included experts from Bristol Uncover GroupAnd the Max Planck Bristol Center for Minimalist BiologyIncidental University of Bristol Hello Therapeutics Ltd, and collaborators in Sweden and France. The studies were supported by funding from Max Planck GesellschaftAnd the Wellcome Trust And the European Research CouncilWith additional support from Oracle Research for high-performance cloud computing resources.



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