Pan-coronavirus Antiviral Treatment

Pan coronavirus Antiviral Treatment
Pan coronavirus Antiviral Therapy - Spike glycoprotein structure of the coronavirus responsible for the 2002 epidemic SARS-CoV. The structure is kept non-infectious when linoleic acid is added. Protein structure and cryo-EM density predicted using cloud computing are displayed (left) (middle). Orange colored linoleic acid molecules are visible. This image shows a zoom of the pocket (boxed) found in all deadly coronaviruses. Credits: Christiane Schaffitzel and Christine Toelzer of the University of Bristol

Pan-coronavirus antiviral treatment may be possible due to the common pocket feature of deadly coronaviruses. The mystery of why some coronaviruses are more prone to causing serious illness has been solved by scientists. The findings of the study, conducted by the University of Bristol and published today [November 23, 2022] in Science Advances, will be effective against all coronaviruses, including the Omicron that caused the 2002 SARS-CoV epidemic, the current SARS-CoV-2 variant, and potentially harmful variants that may emerge in the future. could help develop a pan-coronavirus drug.

The spike glycoproteins that grace each coronavirus have been studied by an international team led by Professor Christiane Schaffitzel from Bristol. They showed that all deadly coronaviruses, including MERS and Omicron, feature a custom-made pocket in the SARS-CoV-2 spike protein first found in 2020. In contrast, coronaviruses, which cause mild illness with cold-like symptoms, lack the pocket feature.

The pocket that binds a small molecule called linoleic acid can now be used to treat all deadly coronaviruses, while simultaneously sensitizing them to a linoleic acid-based treatment that targets this pocket, according to the research team. Linoleic acid is an essential fatty acid required for many cellular functions, including inflammation and the maintenance of cell membranes in the lungs so that we can breathe properly.

After MERS-CoV in 2012 and SARS-CoV in 2002, the third worst coronavirus outbreak is COVID-2, caused by SARS-CoV-19. With more and more new variations emerging as Omicron circumvents immunization and the immune response, the much more contagious SARS-CoV-2 continues to infect humans and wreak havoc on communities and economies around the world.

Professor Schaffitzel, from the University of Bristol's School of Biochemistry, said in a previous study: “We detected the presence of linoleic acid, a small molecule hidden in a specially designed pocket inside the SARS-Cov-2 glycoprotein.

Known as the "spike protein," this molecule binds to the surface of human cells, allowing the virus to enter the cells and begin to multiply, causing great harm.

“We pointed to a potential antiviral remedy by showing that pocketing linoleic acid can prevent viral infectivity. The original Wuhan strain of the pandemic contained it. Since then, a wide variety of dangerous variants of SARS-CoV-2 have emerged, including the now predominant form of concern Omicron. Every new variation of concern was reviewed and we checked to see if the pocket functionality was still available.”

The fact that Omicron has undergone a large number of mutations makes it possible for this rapidly developing virus to evade the immune defense provided by vaccination or antibody treatments that lag behind. Interestingly, the researchers discovered that the pocket remained essentially unchanged in the Omicron, despite the possibility that everything else might have changed.

"When we realized that the pocket we found remained unchanged, we looked back and saw whether SARS-CoV and MERS-CoV, the other two deadly coronaviruses that caused epidemics years ago, also contained this linoleic acid binding pocket feature," said Christine Toelzer, Research Fellow in the School of Biochemistry and lead author of the study. we asked,” he said.

The group used cloud computing, cutting-edge computational methods and high-resolution electron cryo-microscopy. Their findings showed that SARS-CoV and MERS-CoV both have this pocket and can bind linoleic acid in almost the same way.

Finally, Professor Schaffitzel said: “In this study, we show that the pocket is constant in all deadly coronaviruses, from the first SARS-CoV outbreak 20 years ago to the Omicron today.

As we showed earlier, when linoleic acid binds to this site, it causes a locked-in increase that prevents viral infectivity. We also showed that linoleic acid supplementation inhibited viral replication within cells.

Future iterations are also expected to have pockets that we can use to our advantage to stop the infection.”

source: bristol.ac.uk/news

Günceleme: 25/11/2022 12:17

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