Abstract
The outbreak of SARS-CoV-2 in December 2019, led to the ongoing global pandemic of coronavirus disease 2019 (COVID‑19), which has claimed more than a half million lives in a few months. Enormous efforts are being made in developing vaccines and therapeutic treatment to fight against COVID-19. Inactivated SARS-CoV-2 viruses are currently used as vaccine candidates; therefore, it is important to understand the architecture of SARS-CoV-2. We have propagated and purified a clinical strain of SARS-CoV-2 and genetically and structurally characterized β-propiolactone inactivated viruses. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are observed, the majority of viral spikes appear nail-shaped resembling a postfusion state, where S1 protein of the spike has disassociated. Cryo-electron tomography and subtomogram averaging of these spikes yielded a density map which closely matches the overall structure of SARS-CoV S2 spike and their corresponding glycosylation sites. Our findings have major implications in SARS-CoV-2 vaccine design owing to the critical importance of prefusion immunogens.Funding: This work was supported by the Science and Technology Innovation Committee of Shenzhen Municipality(202002073000002), the National Institutes of Health grant P50AI150481 (P.Z.), the UK Wellcome Trust Investigator Award 206422/Z/17/Z(P.Z.), and the UK Biotechnology and Biological Sciences Research Council grant BB/S003339/1 (P.Z.). Conflict of Interest: The authors declare no competing financial or non-financial interests. Ethical Approval: The research received approval from the Research Ethics Committee of Shenzhen Third People's Hospital, China (approval number: 2020-038). The Research Ethics Committee waived the requirement informed consent before the study started because of the urgent need to collect epidemiological and clinical data. We analyzed the data anonymously.
Highlights
Coronaviruses are a large family of zoonotic viruses responsible for multiple large-scale outbreaks in past few decades (Liu et al, 2020; Perlman and Netland, 2009; Yang et al, 2013, 2019)
Since early December of 2019, the outbreak of a pneumonia epidemic was determined to be caused by a novel coronavirus (Wang et al, 2020; Zhu et al, 2020), SARS-CoV-2
The resulting disease caused by SARS-CoV-2 was named coronavirus disease 2019 (COVID-19) (Viruses, 2020)
Summary
Coronaviruses are a large family of zoonotic viruses responsible for multiple large-scale outbreaks in past few decades (Liu et al, 2020; Perlman and Netland, 2009; Yang et al, 2013, 2019). Since early December of 2019, the outbreak of a pneumonia epidemic was determined to be caused by a novel coronavirus (Wang et al, 2020; Zhu et al, 2020), SARS-CoV-2. The resulting disease caused by SARS-CoV-2 was named coronavirus disease 2019 (COVID-19) (Viruses, 2020). As of this writing, more than 11 million confirmed cases of and more than half a million deaths due to COVID-19 have been reported worldwide (WHO, 2020b). Coronaviruses are enveloped single-stranded positive-RNA viruses, roughly 80–120 nm in diameter. The viral RNA is intimately associated with the viral nucleocapsid protein (N), forming large viral ribonucleoprotein complexes. The viral envelope is derived from the host cell and decorated with viral surface proteins: spike (S), membrane (M), and envelope (E)
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