Cryo-EM and cryo-ET of the spike, virion, and antibody neutralization of SARS-CoV-2 and VOCs.

Since the outbreak of the COVID-19 pandemic, cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) have been demonstrated to be powerful and efficient tools in structural studies of distinct conformational states of the trimeric spike protein of SARS-CoV-2 and the VOCs as well as the intact virion. Cryo-EM has also contributed greatly to revealing the molecular basis of receptor recognition and antibody neutralization of the S trimer. Additionally, it has provided structural insights into the enhanced transformation and immune evasion of the VOCs, thus facilitating antiviral antibody and drug discovery. In this review, we summarize the contributions of cryo-EM and cryo-ET in revealing the structures of SARS-CoV-2 S trimer and intact virion and the mechanisms of receptor binding and antibody neutralization. We also highlight their prospective utilities in the development of vaccines and future therapeutics against emerging SARS-CoV-2 variants and other epidemic viruses.