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
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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Structural topological analysis of spike proteins of SARS-CoV-2 variants of concern highlight distinctive amino acid substitution patterns
TL;DR: In this paper , a method of mapping S-protein substitution profile across variants to identify the conserved and AAS regions was proposed, and a substitution matrix was created based on publicly available databases, and the substitution localization was illustrated on a cryo-electron microscopy generated S protein model.
Journal ArticleDOI
Does Covera-19 know 'when to hold 'em or 'when to fold 'em? A translational thought experiment.
TL;DR: The role of pH in extracellular or intracellular protein or actionable requirements of Covera-19 is discussed in this paper, where the pH needs of COVID-19 players and its journey through the human host and environment as well as some efficacious readily available repurposed drugs and out-of-the box and easily available treatments are reviewed.
Journal ArticleDOI
Preserved recognition of Omicron spike following COVID-19 messenger RNA vaccination in pregnancy
Yannic C. Bartsch,C. Atyeo,Jaewon Kang,Yongfei Cai,Bing Chen,Kathryn Gray,Andrea G. Edlow,Galit Alter +7 more
TL;DR: In this paper , the authors tested whether vaccine-induced antibodies raised during pregnancy continue to bind to and leverage Fc receptors to protect against SARS-CoV-2 variants of concern including the Omicron variant.
Journal ArticleDOI
The Physical Basis for pH Sensitivity in Biomolecular Structure and Function, With Application to the Spike Protein of SARS-CoV-2
TL;DR: These aspects are demonstrated with new work on the spike protein of SARS-CoV-2, looking at the pH dependence of variants, including prediction of a change in the balance of locked, closed, and open forms at neutral pH for the Omicron variant spike protein.
Posted ContentDOI
Structural basis for cell-type specific evolution of viral fitness by SARS-CoV-2
Kapil Gupta,Christine Toelzer,Maia Kavanagh Williamson,Deborah K. Shoemark,A. Sofia F. Oliveira,David A. Matthews,Abdulaziz Almuqrin,Oskar Staufer,K.N. Sathish Yadav,Ufuk Borucu,Frederic Garzoni,Daniel J. Fitzgerald,Joachim P. Spatz,Adrian J. Mulholland,Andrew D. Davidson,Christiane Schaffitzel,Imre Berger +16 more
TL;DR: In this paper, the BriSΔ variant of SARS-CoV-2 has an eight amino acid deletion encompassing the furin recognition motif and S1/S2 cleavage site, providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity.
References
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