Three-dimensional reconstruction by electron tomography for the application to ultrastructural analysis of SARS-CoV-2 particles

SARS-CoV-2 is the cause of COVID-19. The three-dimensional morphology of viral particles existing and multiplying in infected cells has not been established by electron tomography, which is different from cryo-electron tomography using frozen samples. In this study, we establish the morphological structure of SARS-CoV-2 particles by three-dimensional reconstruction of images obtained by electron tomography and transmission electron microscopy of biological samples embedded in epoxy resin. The characteristic roots of spike structures were found to be arranged at the surface of a virion covered with an envelope. A high-electron-density structure that appears to be a nucleocapsid was observed inside the envelope of the virion on three-dimensional images reconstructed by electron tomography. The SARS-CoV-2 particles that budded in the vacuoles in the cytoplasm were morphologically identical to those found outside the cells, suggesting that mature and infectious SARS-CoV-2 particles were already produced in the vacuoles. Here, we show the three-dimensional morphological structure of SARS-CoV-2 particles reconstructed by electron tomography. To control infection, inhibition of viral release from vacuoles would be a new target in the development of prophylactic agents against SARS-CoV-2.