期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：48
DOI：10.1073/pnas.2112703118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a severe threat to public health and the global economy. Its spike protein is responsible for the membrane fusion and is thus a major target for vaccine and drug development. Our study presents the in situ structure of the spike protein in the postfusion state with higher resolution, giving further insights into the design of a viral entry inhibitor. Our observation of the oligomerization states of spikes on the viral membrane implies a possible mechanism of membrane fusion for viral infection.
The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates membrane fusion to allow entry of the viral genome into host cells. To understand its detailed entry mechanism and develop a specific entry inhibitor, in situ structural information on the SARS-CoV-2 spike protein in different states is urgent. Here, by using cryo-electron tomography, we observed both prefusion and postfusion spikes in β-propiolactone–inactivated SARS-CoV-2 virions and solved the in situ structure of the postfusion spike at nanometer resolution. Compared to previous reports, the six-helix bundle fusion core, the glycosylation sites, and the location of the transmembrane domain were clearly resolved. We observed oligomerization patterns of the spikes on the viral membrane, likely suggesting a mechanism of fusion pore formation.
