Study details changes in Omicron’s spike protein

Date:

The model of the Omicron variant peplomer shows the location of some of its 37 mutations (red spheres). Credits: David Veesler Lab

An international team of scientists has determined the exact structural changes in the peaplomer of the Omicron variant. Their observations explain how the virus evades antibodies to previous mutants and remains highly infectious.

“The findings provide a blueprint that researchers can use to design new countermeasures, whether vaccines or treatments. Omicron David Wiesler, a researcher at the Howard Hughes Medical Institute and an associate professor of biochemistry at the University of Washington School of Medicine in Seattle, said: He is Vir Biotechnology, Inc. He led the research activities with Gyorgy Snell. In San Francisco.

Researchers report their findings in the journal Chemistry..

Matthew McCallum, a postdoc in Veesler’s lab, and Nadine Czudnochowski, a scientist at Vir Biotechnology, were the lead authors of this paper.

The Omicron variant, first identified in South Africa in November 2021, is causing a proliferation of infections around the world. In addition to being highly infectious, this variant can evade antibodies to previous variants, causing breakthrough infections between vaccinated and previously infected individuals.

The infectivity of the virus is believed to be due, at least in part, to the large number of mutations in the amino acid sequence of the spikes in the virus. protein.. The virus uses spike proteins to latch and invade infected cells. The omicron spike protein has 37 mutations, unlike the first SARS-CoV-2 isolate in 2020.

Previous studies by Veesler and his colleagues have shown six of the most commonly used vaccines and antibodies produced by all but one. Monoclonal antibody It is currently used to treat infectious diseases and has diminished or disabled ability to neutralize Omicron.

However, many mutations in mutants affect the structure of regions of peplomers, called receptor-binding domains, that are involved in cell attachment and invasion, resulting in receptor-binding domain structures. Many expected that changes could be impaired by the ability of the mutant to bind to its target on the cell. This target is a protein called angiotensin converting enzyme-2 or ACE2. However, in their study, Veesler and his colleagues found that this change actually increased the ability of the receptor-binding domain to bind to ACE2 by a factor of 2.4.

To understand how Omicron accumulated many mutations while maintaining efficient interaction with the host receptor ACE2, Veesler and his colleagues worked on cryo-electron microscopy and X-ray crystallography. Studies have been used to reveal the 3D structure of the Omicron spike protein. With this approach, they were able to achieve a resolution of about 3 angstroms. At this resolution, we were able to identify the shape of the individual amino acid building blocks that make up the spike protein. Researchers have also determined how structural changes in peplomers affect the ability of antibodies effective against previous mutants to bind to Omicron.

Using these techniques, scientists have revealed how mutations have altered the way proteins interact with antibodies, reducing the ability of almost all monoclonal antibodies to them while at the same time spike receptors. The binding domain’s ability to bind to ACE2 has been reduced and enhanced. The overall effect was to allow the receptor binding domain to evade antibodies that target it and bind more strongly to ACE2.

The findings show what the formidable enemy SARS-CoV-2 is, says Veesler.

“This virus has incredible plasticity. It can change a lot and maintain all the functions needed for infection and replication,” he said. “And it’s almost guaranteed that Omicron isn’t the last variant we see.”

My future goal is spike A protein that cannot be altered without losing its function, Veesler said. Due to their importance, these regions tend to remain conserved as other parts of the protein mutate.

Therefore, such conserved regions of viral proteins are likely to remain unchanged in new ones. Mutant It may appear. These regions are ideal for new vaccines and treatments that may be effective not only against new variants, but also against new salbecoviruses, a group of viruses including SARS-CoV-2 and SARS-CoV. Veesler said it would be a good target.


Antibodies that inhibit a wide range of salvecoviruses found


For more information:
David Veesler et al, SARS-CoV-2 Omicron Structural Foundation for Antigenic Evasion and Receptor Involvement, Chemistry (2022). DOI: 10.1126 / science.abn8652

Quote: Https: //medicalxpress.com/news/2022-01-omicron-spike-protein.html Details of the study of Omicron’s Peplomer (January 25, 2022) obtained on January 25, 2022. Change

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