Molecular Architecture of the SARS-CoV-2 Virus

SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryoelectron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in pre- and postfusion conformations were determined to average resolutions of 8.7–11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed overall processing states of the native glycans highly similar to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNPs) and their higher-order assemblies were revealed. Overall, these characterizations revealed the architecture of the SARS-CoV-2 virus in exceptional detail and shed light on how the virus packs its ∼30-kb-long single-segmented RNA in the ∼80-nm-diameter lumen. [Display omitted] •Molecular architecture of the authentic SARS-CoV-2 virus•Native structures of S in RBD down, one RBD up, and postfusion conformations•Compositions of the glycans from the native S are characterized by mass spectrometry•Structure and assembly of the RNPs are revealed in situ Combined imaging analyses of 2,294 intact virions from the authentic SARS-CoV-2 virus resolve the S protein in pre- and postfusion conformations and characterize the molecular architecture of SARS-CoV-2 at high resolution.