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, cr yo-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. Cr yo-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 cr yo-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 SARSCoV-2 variants and other epidemic viruses.

Automated summary

Since the COVID-19 pandemic began, cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) have been shown to be powerful tools in studying the structure of SARS-CoV-2 spike protein and the intact virion, as well as understanding receptor binding and antibody neutralization. They have also provided insights into the enhanced transformation and immune evasion of variants, aiding in the discovery of antibodies and drugs. This review summarizes the contributions of cryo-EM and cryo-ET in revealing the structures and mechanisms of SARS-CoV-2, as well as their potential in developing vaccines and therapeutics against emerging variants.