Abstract

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 and the complexes of the spike with the cellular receptor ACE2 or neutralizing antibodies, detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryo-electron tomography and subtomogram averaging. Native structures of the S proteins in both pre- and postfusion conformations were determined to average resolutions of 9-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass-spectrometry. The native architecture of the ribonucleoproteins and its higher-order assemblies were revealed. These characterizations have revealed the architecture of the SARS-CoV-2 virus to an unprecedented resolution, and shed lights on how the virus packs its ~30 Kb long single-segmented RNA in its lumen. Overall, the results unveiled the molecular architecture of the SARS-CoV-2 in native context.Funding: This work was supported in part by funds from Major Project of Zhejiang Provincial Science and Technology Department #2020C03123-1, and National Science and Technology Major Project for the Control and Prevention of Major Infectious Diseases in China (#2018ZX10711001, #2018ZX10102001).Conflict of Interest: The authors declare no competing interests.

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