The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by Cryo-EM and Cryo-ET

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; theref...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Structure (London) 2020-11, Vol.28 (11), p.1218-1224.e4
Hauptverfasser: Liu, Chuang, Mendonça, Luiza, Yang, Yang, Gao, Yuanzhu, Shen, Chenguang, Liu, Jiwei, Ni, Tao, Ju, Bin, Liu, Congcong, Tang, Xian, Wei, Jinli, Ma, Xiaomin, Zhu, Yanan, Liu, Weilong, Xu, Shuman, Liu, Yingxia, Yuan, Jing, Wu, Jing, Liu, Zheng, Zhang, Zheng, Liu, Lei, Wang, Peiyi, Zhang, Peijun
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; therefore, it is important to understand the architecture of inactivated SARS-CoV-2. We have genetically and structurally characterized β-propiolactone-inactivated viruses from a propagated and purified clinical strain of SARS-CoV-2. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are found, most spikes appear nail shaped, thus resembling a postfusion state, where the S1 protein of the spike has disassociated from S2. Cryoelectron tomography and subtomogram averaging of these spikes yielded a density map that closely matches the overall structure of the SARS-CoV postfusion spike and its corresponding glycosylation site. Our findings have major implications for SARS-CoV-2 vaccine design, especially those using inactivated viruses. [Display omitted] •β-propiolactone-inactivated SARS-CoV-2 viruses display postfusion spikes•Cryo-ET structure of SARS-CoV-2 postfusion spikes was determined at 11 Å resolution•This study calls for crucial structural characterization of vaccine candidates Several vaccine candidates using inactivated SARS-CoV-2 viruses are under development. Liu et al. used state-of-the-art cryoelectron microscopy technologies to characterize the architecture of inactivated SARS-CoV-2 viruses. They found that the viral spikes are mostly in a postfusion state, which is not desirable for vaccine development.
ISSN:0969-2126
1878-4186
DOI:10.1016/j.str.2020.10.001