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Scientists get the most realistic view of the protein structure of coronavirus spikes-ScienceDaily

Scientists get the most realistic view of the protein structure of coronavirus spikes-ScienceDaily

 


Coronaviruses that cause COVID-19 are studded with “spike” proteins that bind to receptors on the victim’s cells, the first step in infection. Scientists have now created the first detailed images of spikes in their natural state, without the use of chemical fixatives that can distort the shape while still attached to the virus.

Their method, which combines cryo-electron microscopy (cryo-EM) and calculations, is an important step in designing therapeutic agents and vaccines, faster infectious devices in various strains of coronavirus. Says that it should produce a more realistic snapshot.

“The advantage of doing this method is that purifying the spiked protein and studying it alone loses an important biological background. What does it look like with intact viral particles? DOE’s SLAC National Wouchiu, a professor at the Accelerator Institute and Stanford University and a senior author of the study, said: They described their results. Quarterly Review Biophysical Discovery..

Seven strains of coronavirus are known to infect humans. Four cause relatively mild illness. The other three, including SARS-CoV-2, the virus that causes COVID-19, can be fatal, co-author Jin Jin, an expert in molecular biology of viruses at the Vitalant Institute in San Francisco. He said he had sex. Vitalant scientists look for viruses in human and animal blood and stool samples, screen blood samples during current pandemic-like outbreaks, and study the interaction of the virus with its host.

The virus that causes COVID-19 is so virulent that only a few cryo-EM labs in the world can study it with sufficiently high levels of biosafety control, Jin said. Therefore, in this study, the research team examined a much milder coronavirus strain called NL63. It causes common cold symptoms and causes about 10% of human respiratory illnesses each year. It is thought to attach to the same human cell surface receptors as the COVID-19 virus.

Instead of chemically removing and purifying the NL63 peplomer, researchers flash-frozen the entire intact virus into a glassy state to maintain the natural placement of its constituents. Then, using the cryo-EM equipment at the Stanford-SLAC Cryo-EM facility, we created thousands of detailed images of randomly directed viruses, digitally extracted bits containing spike proteins, and extracted them. I got a high resolution image in combination.

“The structure we saw was exactly the same as the surface of the virus, with no chemical artifacts,” said Jin. “This wasn’t done before.”

The team also identified where sugar molecules attach to peplomer proteins in a process called glycosylation. It plays an important role in the life cycle of the virus and its ability to evade the immune system. Their map contained three glycosylation sites that were predicted but not directly visible.

The German group used a similar method to digitally extract images of the spiked protein from SARS-CoV-2, but Jin infects anyone because the virus had to be modified with formaldehyde. There was no danger. It can cause chemical changes that prevent you from seeing the true structure.

The team said they would like to investigate how the parts of the spikes that bind to receptors in human cells are activated and use the same technique to study spike proteins from viruses that cause COVID-19. I did. A special biohazard containment facility is required.

This study was funded by the Coronavirus CARES method and funded by the National Institutes of Health and the Department of DOE Science through the National Institute of Virtual Biotechnology, a consortium of DOE National Institutes focused on responding to COVID-19. it was done.

Story source:

Materials provided by DOE / SLAC National Accelerator Laboratory.. Original written by Glenda Chui. Note: The content can be edited in style and length.

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