Cryo-EM structure of the SARS-CoV-2 Omicron spike

The recently reported B.1 1.529 Omicron variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 34 mutations in the spike protein relative to the Wuhan strain, including 15 mutations in the receptor-binding domain (RBD). Functional studies have shown Omicron to substantially escape the activity of many SARS-CoV-2-neutralizing antibodies. Here, we report a 3.1 angstrom-resolution cryoelectron microscopy (cryo-EM) structure of the Omicron spike protein ectodomain. The structure depicts a spike that is exclusively in the 1-RBD-up conformation with high mobility of RBD. Many mutations cause steric clashes and/or altered interactions at antibody-binding surfaces, whereas others mediate changes of the spike structure in local regions to interfere with antibody recognition. Overall, the structure of the Omicron spike reveals how mutations alter its conformation and explains its extraordinary ability to evade neutralizing antibodies.

Automated summary

The Omicron variant of SARS-CoV-2, known for its high ability to evade neutralizing antibodies, has been found to have 34 mutations in the spike protein, with 15 of them occurring in the receptor-binding domain (RBD). A cryo-EM structure of the Omicron spike protein reveals that it is exclusively in the 1-RBD-up conformation, with high mobility of RBD. These mutations in the spike protein cause steric clashes and altered interactions at antibody-binding surfaces, as well as changes in local regions that interfere with antibody recognition.