Study reveals structural changes in Alpha and Beta variants of SARS-CoV-2

New variants of SARS-CoV-2 are spreading rapidly and there are concerns that current COVID-19 vaccines will not protect against them. The latest in a series of structural studies on the spike protein of SARS-CoV-2 variants, led by Bing Chen, PhD, at Boston Children’s Hospital, reveals new properties of the Alpha (formerly UK) and Beta (formerly South Africa) variants. Note that this suggests that current vaccines may be less effective against the beta variant.

The advanced proteins on the surface of SARS CoV-2 allow the virus to attach and enter our cells, and all current vaccines are directed against them. The new study, Posted in Science June 24, used electron cryomicroscopy (cryo-EM) to compare the spike protein of the original virus with that of the Alpha and Beta variants.

Structural findings indicate that mutations in the beta variant (also known as B.1.351) change the shape of the tip surface in some places. As a result, the neutralizing antibodies induced by current vaccines are less able to bind to the beta virus, which may allow it to escape the immune system even when people are vaccinated.

“The mutations make the antibodies stimulated by the current vaccine less effective,” says Chen, of the Molecular Medicine division of Boston Children’s. “The beta variant is somewhat resistant to current vaccines, and we believe that a boost with the new genetic sequence may be beneficial in protecting against this variant.”

However, the study also found that mutations in the beta variant make the peak less efficient at binding to ACE2, suggesting that this variant is less transmissible than the Alpha variant.

Reassurance on the Alpha variant; more variant studies in progress

As for the Alpha variant (B.1.1.7), the study confirms that a genetic modification of the peak (a single amino acid substitution) helps the virus to bind better to ACE2 receptors, making it more infectious. However, tests indicate that antibodies induced by existing vaccines can still neutralize this variant.

To pose an increased threat, researchers say, a variant of SARS-CoV-2 would have to do three things: spread more easily, evade the immune system of those vaccinated or those previously exposed to COVID-19, and cause more serious illness. . Fortunately, the Alpha and Beta variants do not meet all of 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.

Chen’s team also plans to report the structures of other variants of concern, including the Delta variant (B.1.617.2), in the near future. These investigations are still ongoing.

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Yongfei Cai, PhD, Jun Zhang, PhD, and Tianshu Xiao, PhD of Boston Children’s Hospital were co-first authors of the article. The study was funded by Emergent Ventures, the Massachusetts Consortium on Pathogen Readiness, and the National Institutes of Health (grants AI147884, AI141002, and AI127193).

About Boston Children’s Hospital

Boston Children’s Hospital is ranked # 1 children’s hospitals in the nation by US News & World Report and is Harvard Medical School’s premier pediatric education affiliate. Home to the world’s largest pediatric medical center-based research company, its findings have benefited both children and adults since 1869. Today, 3,000 researchers and scientific staff, including 9 members of the National Academy of Sciences, 23 members of the National Academy of Medicine and 12 Howard Hughes medical researchers form the Boston Children’s research community. Founded as a 20-bed children’s hospital, Boston Children’s is now a comprehensive 415-bed center for pediatric and adolescent health care. To learn more, visit our Answers blog and follow us on social media @BostonChildrens, @BCH_Innovation, Facebook and Youtube.

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