Distinct conformational states of SARS-CoV-2 spike protein
Yongfei Cai,Yongfei Cai,Jun Zhang,Jun Zhang,Tianshu Xiao,Tianshu Xiao,Hanqin Peng,Sarah M. Sterling,Richard M. Walsh,Shaun Rawson,Sophia Rits-Volloch,Bing Chen,Bing Chen +12 more
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TLDR
Two cryo–electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion and postfusion conformations, are reported, advancing the understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.Abstract:
Intervention strategies are urgently needed to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here, we report two cryo-electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion (2.9-angstrom resolution) and postfusion (3.0-angstrom resolution) conformations, respectively. The spontaneous transition to the postfusion state is independent of target cells. The prefusion trimer has three receptor-binding domains clamped down by a segment adjacent to the fusion peptide. The postfusion structure is strategically decorated by N-linked glycans, suggesting possible protective roles against host immune responses and harsh external conditions. These findings advance our understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.read more
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Full-Length Computational Model of the SARS-CoV-2 Spike Protein and Its Implications for a Viral Membrane Fusion Mechanism.
Wataru Nishima,Marta Kulik +1 more
TL;DR: In this paper, a membrane fusion model incorporating structural transitions associated with the proteolytic processing of the spike protein, which initiates and regulates a series of events to facilitate membrane fusion and viral genome uptake is proposed.
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Bluetongue virus capsid protein VP5 perforates membranes at low endosomal pH during viral entry.
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TL;DR: It was concluded that COVID-19 vaccines might be developed both for immunising high-risk groups and for mass immunisation, and an optimal solution for the second task would be to develop human or monkey adenovirus vector-based vaccines whose mass production has already been unveiled.
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Middle East respiratory syndrome coronavirus Spike protein variants exhibit geographic differences in virulence.
Lok-Yin Roy Wong,Jian Zheng,Alan Sariol,Shea A. Lowery,David K. Meyerholz,Tom Gallagher,Stanley Perlman +6 more
TL;DR: Kim et al. as discussed by the authors constructed isogenic viruses expressing mutations found in the Spike (S) protein from Korean isolates and showed that isogenic virus carrying the Korean MERS-CoV mutations, D510G or I529T, were attenuated in mice, resulting in greater survival, less induction of inflammatory cytokines, and less severe lung injury.
References
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