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Structural studies of the SARS-CoV-2 peplomer reveal new properties of alpha and beta mutants

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New SARS-CoV-2 mutants are spreading rapidly, and there are concerns that current COVID-19 vaccines may not be able to prevent them. The latest in a series of structural studies of the “peplomer” protein of the SARS-CoV-2 mutant, led by Dr. Bing Chen at the Boston Children’s Hospital, reveals new properties of alpha (formerly UK) and beta (formerly South Africa). I am doing it. )variant. Notably, it suggests that current vaccines may not be very effective against beta mutants.

Peplomers on the surface of SARS CoV-2 allow viruses to attach and invade cells, and all current vaccines are directed against them.New research published in Science On June 24, a cryo-electron microscope (cryo-EM) was used to compare the original viral peplomer with alpha and beta variants.

Structural findings indicate that mutations in the beta variant (also known as B.1.351) alter the shape of the spike surface at specific locations. as a result, Neutralizing antibody Those induced by current vaccines cannot bind to the beta virus, which may allow it to evade the immune system even when people are vaccinated.

“Mutations reduce the effectiveness of antibodies stimulated by current vaccines,” says Chen of the Molecular Medicine Department at Boston Children’s. “Beta mutants are somewhat resistant to current vaccines, and we believe that boosters with new sequences will be beneficial in protecting against this mutant.”

However, the study also found that mutations in beta mutants reduced the effectiveness of spikes in binding to ACE2. This suggests that this mutant is less contagious than the alpha mutant.

Reassurance of alpha variants; more variant research underway

For alpha mutants (B.1.1.7), this study confirmed that genetic alterations in spikes (single amino acid substitutions) promoted viral binding to the ACE2 receptor and increased infectivity. I am. However, tests have shown that antibodies elicited by existing vaccines can neutralize this mutant.

To increase the threat, SARS-CoV-2 variants cause more serious illnesses that spread more easily, evade the immune system of vaccinated and previously exposed individuals. Researchers say that they need to do three things. Fortunately, alpha and beta do not meet all of these criteria.

“Our data suggest that the most problematic combination of such mutations does not yet exist in the existing mutants examined here,” the researchers write. ..

Chen’s team also plans to report the structure of other variants of concern, including the Delta variant (B.1.617.2), in the near future. Their investigation is still underway.

Source:

Journal reference:

Kai, Y. , et al. (2021) Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 mutants. Science. doi.org/10.1126/science.abi9745..

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