[Cell Journal] New breakthrough in anti-epidemic! Using yeast screening method-identification of new coronavirus S protein escape mutants

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Author: Daisy Introduction: If human cells are compared to a strong defense city, then the S protein is the "siege hammer" for the new crown virus to invade this city
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Recently, researchers have used yeast screening to identify mutations in the new coronavirus S protein that prevent antibodies from functioning, which will help accelerate the development of a universal vaccine for all viruses
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Researchers at the University of Colorado Boulder have developed a platform that can quickly identify common mutations in the SARS-COV-2 virus
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The "One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening" study published by researchers recently on Cell Reports marks an important step towards the successful development of a universal vaccine , This vaccine is not only suitable for the new coronavirus, but may also target influenza, HIV and other deadly global viruses
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Timothy Whitehead, the lead author of the study and associate professor of chemical and biological engineering, said: "We have developed a predictive tool that can tell you in advance which antibodies are effective against virus strains
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But the significance of this technology is more far-reaching: if you can predict In a certain season, you can be vaccinated to match the sequence that will occur and shorten this seasonal change
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"So what is the "secret recipe" of the research team? ——"Bakery Yeast"
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As we all know, the spike protein (S protein) is an important marker protein on the surface of the virus.
It is a homotrimer of three identical subunits combined by non-covalent bonds; at the same time, the S protein has multiple N-glycosylation sites.
Point, glycosyls are connected to proteins by covalent bonds to form glycoproteins, and the presence of a large number of glycosyls can change the spatial structure of protein molecules through glycosylation to block or destroy epitopes, thereby inhibiting the body’s immune response to viruses.
Play a protective role
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Researchers have developed a genetically modified version of this harmless substance, expressing some SARS-CoV-2 virus spike proteins on the surface of yeast.
Using these proteins, they can map the mutations that form and evade neutralizing antibodies
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Whitehead said: "The resulting roadmap can provide information for the development of more effective booster vaccines and customized antibody treatments for severely ill patients with the new coronavirus
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" Spike proteins are sharp protrusions from the surface of the virus in the coronavirus family
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Under the microscope, they can appear like coronaviruses, which is how the coronavirus (corona means "crown" in Latin) is named
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When antibodies recognize, lock and prevent them from binding to cells, they can prevent infection
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But when the spike protein is mutated, the antibody has a dual effect
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Whitehead said: "There is a mutation in the spike protein that prevents the antibody from entering and recognizing it
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It's
like a new hair>
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" In 2021 Among the more infectious Delta variants that appeared in 2015, mutations in the spike protein made it more infectious and reduced the efficacy of some antibody therapies
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So is there a way to predict which mutations will occur next, so as to prepare for them? Earlier this year, Whitehead's team started looking for a way
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Whitehead said: "Some antibodies that can bind to different positions have been used in cocktail therapy for patients with new coronavirus
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But the virus strains currently circulating in the United States are very different, and some antibody therapies seem to be no longer effective
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" Therefore, researchers need First identify the spike protein mutations that might prevent these antibodies from working
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Then they want to predict what mutations might happen next, and what might become variants of zeta, eta, or theta? The paper’s co-author, chemical and biological engineering graduate student and Balsells researcher Irene Francino Urdaniz said: “When the pandemic started, we saw an opportunity to apply the technology in our laboratory to make a contribution
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According to my research, when detected When a new mutation is present, I can most of the time guess which mutations exist
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I am very excited.
My work has not only contributed to this pandemic, but may also contribute to future vaccines
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" Francino Urdaniz Developed A genetically engineered strain of common baker's yeast, which can display different parts of the viral spike protein on its surface
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Then, she discovered how to screen thousands of mutations in a test tube to find mutations that evade neutralizing antibodies
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In 2020, some people who bake at home found that yeast grows very fast when experimenting with yeast starters
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This means that researchers can see all kinds of mutations develop at the same rate, and yeast grows faster than mutations appear in real time
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This can give scientists a valuable start
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Researchers have discovered some of the same mutations, which are currently spreading globally, and have discovered more mutations that may evade the immune system
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They will also provide all the information, methods and software libraries as a publicly available community resource to accelerate new treatment strategies against the SARS-CoV-2 virus
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This means that the next new coronavirus vaccine or booster produced for the public may have as much power as possible
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It also brings hope to those who have weakened immune function or still have a higher risk of infection.
This research can be used to actively prepare antibody therapies for specific mutations, so that they have a better chance of survival and recovery
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But it doesn't stop there
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Whitehead said: "Because of the adaptability of the new mRNA vaccine working with the spike protein, the application of this research is not limited to one virus
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You can use it to map the trajectory of influenza and HIV; for other known Viral diseases, and possible pandemic diseases
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"Reference materials: 1.
https://medicalxpress.
com/news/2021-08-mutation-mapping-tool-yield-stronger-covid.
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https:// Note: This article Aims to introduce the progress of medical research and cannot be used as a reference for treatment plans
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If you need health guidance, please go to a regular hospital
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