Structural characterization of β-propiolactone inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particles

The severe COVID-19 pandemic drives the research toward the SARS-CoV-2 virion structure and the possible therapies against it. Here, we characterized the beta-propiolactone inactivated SARS-CoV-2 virions using transmission electron microscopy (TEM) and atomic force microscopy (AFM). We compared the SARS-CoV-2 samples purified by two consecutive chromatographic procedures (size exclusion chromatography [SEC], followed by ion-exchange chromatography [IEC]) with samples purified by ultracentrifugation. The samples prepared using SEC and IEC retained more spikes on the surface than the ones prepared using ultracentrifugation, as confirmed by TEM and AFM. TEM showed that the spike (S) proteins were in the pre-fusion conformation. Notably, the S proteins could be recognized by specific monoclonal antibodies. Analytical TEM showed that the inactivated virions retained nucleic acid. Altogether, we demonstrated that the inactivated SARS-CoV-2 virions retain the structural features of native viruses and provide a prospective vaccine candidate.

Automated summary

This study characterized the beta-propiolactone inactivated SARS-CoV-2 virions using TEM and AFM, finding that samples prepared using SEC and IEC retained more spikes on the surface and the S proteins were in the pre-fusion conformation. Analytical TEM showed that the inactivated virions retained nucleic acid, demonstrating their potential as a vaccine candidate.