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Location similarity, mutation types may signal future reactions to SARS-CoV-2 strains-ScienceDaily

 


A new study from the University of Nebraska-Lincoln suggests that mutations in the SARS-CoV-2 virus that cause COVID-19 occur in the coronavirus genus, which is the most dangerous to families, or at least humans. ..

The Nebraska team compared the early evolution of SARS-CoV-2 with the evolution of its closest relative, beta-coronavirus, after which the SARS-CoV-2 mutation was genetically and structurally essentially I found it happening in the same place.

Researchers have found that the mutational similarity between SARS-CoV-2 and its predecessors, including SARS-CoV-1 and MERS-CoV, which infect humans, is how the virus that causes COVID evolves. He said it could help predict whether to continue.

Catherine La Tourette, a PhD student in the Nebraska Complex Biosystems Program, said: “By looking at this big picture, we were able to predict the nature of the SARS-CoV-2 mutation.

“It goes into these questions: are vaccines effective in the long run? Which varieties will creep in? Do we need that booster shot? Will vaccinated people get infected a second time? ? “

“You are likely to hit that bullseye.”

The genetic code of the virus determines its ability to infect cells and direct them to produce larger copies of themselves. The code is composed of basic compounds or nucleotides, and mutations occur each time those nucleotides are added, subtracted, or exchanged with each other. Many changes have little or no effect, just as attempts to hack complex passwords by changing only one character are likely to fail.

However, with sufficient chance, the virus is ultimately generated by mutations that alter its structural joints or sets of amino acids, enough to promote cell invasion and replication. This is an advantage that helps to beat other stocks. In some cases, new strains can also circumvent the immune response evoked by existing vaccines, requiring the development of new vaccines to prevent them.

La Tourrette and her adviser Hernan Garcia-Ruiz were busy comparing mutation patterns across viruses that invaded plants in different biological kingdoms during the SARS-CoV-2 pandemic. To do so, researchers were analyzing segments of DNA sequenced from parallel locations on the genome of all viruses within the genus. They were especially looking for single-point mutations, that is, segments in which only one nucleotide was altered. By identifying them, the team speculated whether specific mutations would appear throughout the associated plant virus and tracked those mutations down to functional amino acid changes in the virus.

“Often researchers have a particular plant virus they study,” La Tourette said. “They know it really well. But our question is, the big picture, what the genus is doing? We know that the changes are not random. It accumulates in specific regions of the genome. However, those areas are (sometimes) consistent across the genus. These tend to be important areas for host adaptation, etc. Basically, they change to continue co-evolution with the host. This is the area that needs to be continued.

“So when COVID-19 happened, I thought we could download the (betacoronavirus) sequence and pipe it through the pipeline to see where the mutation was happening.”

When they did, La Tourrette and her colleagues found that SARS-CoV-2 is a so-called peplomer that is key to invasion of host cells by protruding from betacoronavirus and binding to superficial receptors. We have found that it mutates rapidly across all known betacoronaviruses.

Researchers have found that “hypervariable” peplomers accumulate about 50% of all mutations in the virus, even though they make up only 17% of the SARS-CoV-2 genome. These mutations, like all other betacoronaviruses to date, occur in the same region of the genome, as well as in the same subunit of peplomer.

“All our analysis has shown that it is where the fluctuations are actually happening,” La Tourrette said. “When we saw it, it didn’t matter which mutant we saw-the peplomer was the key.”

The team also concluded that the SARS-CoV-2 peplomer is disordered, as other virologists have-the amino acids are assembled into the same general architecture, but in that architecture What La Tourrette called “some wiggle rooms” shifts slightly in different configurations. That’s bad news, she said, given that structural flexibility can give room for functional wiggles.

“Human may have slightly different cell receptors from person to person,” La Tourrette said. “Then we need a (spiked protein) receptor that can accommodate those small shifts. If it was so ordered that we couldn’t shift, we probably couldn’t infect everyone. But With its flexibility, it’s a much better virus.

“Basically, this area is very variable and flexible, so it’s a double pain.”

According to LaTourrette, these qualities will make SARS-CoV-2 a formidable enemy that needs to be vigilant for the foreseeable future. However, knowing its strengths and knowing that the evolutionary history of other beta coronaviruses may serve as a rational preview of its future will help virologists and vaccinologists develop strategies accordingly. must.

As SARS-CoV-2 evolves, vaccines may need to continue to target characteristic peplomers, but investigating betacoronavirus mutation patterns can mutate which domain of the protein. Helps researchers predict whether is the highest or lowest. According to LaTourrette, this could make it much easier to attack moving targets.

“If you close your eyes when throwing darts on a darts board, you can go anywhere,” she said. “But if you look at the other (beta coronavirus) species, you can see where they are likely to land, and they are more likely to be eye-opening.”

LaTourrette has already returned to the botanical world, but at a time of lack of satisfaction, she proved to be satisfied with the opportunity to adapt her work to such an urgent purpose. Told.

“For us, (migrating) from plants to the coronavirus was a really positive way to show that you can incorporate your science and knowledge and apply it to the interests of society,” La Tourette said. Said. “In the last year and a half, I’ve seen some really great examples of that change.

“This is a very difficult time and there are many difficulties, but I think it’s really positive to see scientists come together and contribute to the cause together.”

Garcia-Ruiz, associate professor of phytopathology at the La Tourrette and Nebraska Center for Virology, is a recent master’s graduate Natalie Holste, a doctoral student Rosalba Rodriguez-Peña, and a visiting researcher from Brazil, Raquel Arruda Leme. I did research with.

A team supported by the National Institutes of Health and the United States Department of Agriculture’s National Institute of Food and Agriculture recently published the findings. Virology Journal..

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2/ https://www.sciencedaily.com/releases/2021/07/210713145755.htm

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