Understanding SARS-CoV-2 variants by Cryo-EM

Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains in the COVID-19 pandemic. Dr. Bing Chen and his colleagues from Harvard Medical School have determined cryo-EM structures of the full-length spike (S) trimers of the Alpha, Beta, Gamma, Kappa and Delta variants, and studied their function and antigenic properties.

Dr. Chen will discuss his latest research in this webinar:

· Mutations in the Alpha protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2), possibly accounting for its increased transmissibility.

· The Beta variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, making it resistant to potent neutralizing antibodies.

· Delta S can fuse membranes more efficiently at low levels of cellular receptor ACE2 and its pseudotyped viruses infect target cells substantially faster than the other five variants possibly accounting for its heightened transmissibility.

Dr. Chen and his colleagues have found out that each variant shows different rearrangement of the antigenic surface of the N-terminal domain of the S protein, but only cause local changes in the receptor-binding domain, making the receptor-binding domain (RBD) a better target for therapeutic antibodies. These findings provide structural details on how SARS-CoV-2 has evolved to enhance viral fitness and immune evasion.