Nanometer-resolution in situ structure of the SARS-CoV-2 postfusion spike protein

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates membrane fusion to allow entry of the viral genome into host cells. To understand its detailed entry mechanism and develop a specific entry inhibitor, in situ structural information on the SARS-CoV-2 spike protein in different states is urgent. Here, by using cryo-electron tomography, we observed both prefusion and postfusion spikes in beta-propiolactone-inactivated SARS-CoV-2 virions and solved the in situ structure of the postfusion spike at nanometer resolution. Compared to previous reports, the six-helix bundle fusion core, the glycosylation sites, and the location of the transmembrane domain were clearly resolved. We observed oligomerization patterns of the spikes on the viral membrane, likely suggesting a mechanism of fusion pore formation.

Automated summary

By utilizing cryo-electron tomography, researchers observed prefusion and postfusion spikes in beta-propiolactone-inactivated SARS-CoV-2 virions, and successfully solved the in situ structure of the postfusion spike at nanometer resolution. The study provided detailed information on the fusion core, glycosylation sites, and transmembrane domain location, shedding light on the mechanism of fusion pore formation through spike oligomerization patterns on the viral membrane.