Structural changes in SARS-CoV-2 Alpha and Beta variants revealed

A structural biology study has revealed new properties of the SARS-CoV-2 Spike (S) protein of the Alpha and Beta variants of the virus. According to the researchers, from Boston Children’s Hospital, US, the findings suggest that current vaccines may be less effective against the Beta variant.

S proteins, on the surface of SARS CoV-2, are what enable the virus to attach to and enter cells and all current vaccines are directed against them. Using cryo-electron microscopy (cryo-EM), the team compared the S protein from the original virus with that the Alpha and Beta variants.

The findings indicate that mutations in the Beta variant (also known as B.1.351) change the shape of the S protein surface at certain locations. As a result, neutralising antibodies induced by current vaccines are less able to bind to the Beta virus, which may allow it to evade the immune system even when people are vaccinated.

“The mutations make antibodies stimulated by the current vaccine less effective,” said Dr Bing Chen, who led the research. “The Beta variant is somewhat resistant to the current vaccines and we think a booster with the new genetic sequence can be beneficial for protecting against this variant.”

However, the study also found that mutations in the Beta variant make the S protein less effective in binding to angiotensin-converting enzyme 2 (ACE2), suggesting that this variant is less transmissible than the Alpha variant.

Mutations in the SARS-CoV-2 variants cause changes in the electrostatic potential (electric charge at rest) on the S surface. Here, positively charged areas are shown in blue and negatively charged areas in red. In the Beta variant, the receptor-binding domain (RBD) and N-terminal domain (NTD) have changed substantially, affecting the ability of antibodies to bind to and neutralise the virus [credit: Dr Bing Chen, Boston Children’s Hospital].

As for the Alpha variant (B.1.1.7), the study confirms that a genetic change in the S protein (a single amino acid substitution) helps the virus bind better to ACE2 receptors, making it more infectious. However, testing indicates that antibodies elicited by existing vaccines can still neutralise this variant.

To be a heightened threat, the researchers say, a SARS-CoV-2 variant would need to:

• spread more easily
• evade the immune system in vaccinated people or those previously exposed to COVID-19
• cause more severe disease.

The researchers say that fortunately, the Alpha and Beta variants do not meet all these criteria.

“Our data suggest that the most problematic combination of such mutations is not yet present in the existing variants examined here,” the researchers write.

The team also plans to report the structures of other variants of concern, including the Delta variant (B.1.617.2), in the near future. Those investigations are under way.

The study is published in Science.