Supramolecular Architecture of Severe Acute Respiratory Syndrome Coronavirus Revealed by Electron Cryomicroscopy

TLDR

Coronavirus particles are enveloped and pleomorphic, making them refractory to crystallization and symmetry‑assisted reconstruction. The study aims to model the oligomeric state and spatial relationships among SARS‑CoV structural proteins using a novel single‑particle image analysis method. A novel single‑particle image analysis technique was applied to selected virus features to generate a detailed model of the viral architecture. The analysis resolved SARS‑CoV structural proteins to ~4 nm, revealing overlapping lattices of membrane‑associated proteins, spike–ribonucleoprotein registration, and coiled ribonucleoprotein cores, showing that spikes are not required for lattice formation and providing the first detailed view of coronavirus ultrastructure.

Abstract

ABSTRACT Coronavirus particles are enveloped and pleomorphic and are thus refractory to crystallization and symmetry-assisted reconstruction. A novel methodology of single-particle image analysis was applied to selected virus features to obtain a detailed model of the oligomeric state and spatial relationships among viral structural proteins. Two-dimensional images of the S, M, and N structural proteins of severe acute respiratory syndrome coronavirus and two other coronaviruses were refined to a resolution of ∼4 nm. Proteins near the viral membrane were arranged in overlapping lattices surrounding a disordered core. Trimeric glycoprotein spikes were in register with four underlying ribonucleoprotein densities. However, the spikes were dispensable for ribonucleoprotein lattice formation. The ribonucleoprotein particles displayed coiled shapes when released from the viral membrane. Our results contribute to the understanding of the assembly pathway used by coronaviruses and other pleomorphic viruses and provide the first detailed view of coronavirus ultrastructure.