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
Citations
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Journal ArticleDOI
Yeast display of MHC-II enables rapid identification of peptide ligands from protein antigens (RIPPA).
TL;DR: In this article, the authors identify protein-derived peptide ligands that constitute epitopes for T cell recognition using direct flow cytometry-based screening of peptides from selected antigens.
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Evaluation of Interactions between SARS-CoV-2 RBD and Full-Length ACE2 with Coarse-Grained Molecular Dynamics Simulations
TL;DR: The results indicated that the plier structure in two ends of the binding interface plays a key role in the binding process of SARS-CoV-2 RBD with ACE2 and it is found that when there is no B0AT1 in the simulation system, the N-terminus of ACE2 is more likely to approach the cell membrane, which has a strong correlation with the subsequent fusion of the virus with the cell membranes.
Posted ContentDOI
Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2
TL;DR: In this paper, the authors used an extensive set of unbiased and biased microsecond-level all-atom molecular dynamics simulations of SARS-CoV-1 and 2 spike proteins to determine the differential dynamic behavior of prefusion spike protein structure in the two viruses.
Journal ArticleDOI
Targeting the Fusion Process of SARS-CoV-2 Infection by Small Molecule Inhibitors
Seung Bum Park,Parker H. Irvin,Zongyi Hu,Mohsin Khan,Xin Hu,Qiru Zeng,Catherine Chen,Miao Xu,Madeleine Leek,Ruochen Zang,James Brett Case,Wei Zheng,Siyuan Ding,T. Jake Liang +13 more
TL;DR: Two hepatitis C virus (HCV) fusion inhibitors identified in a previous study broadly block human coronavirus entry into various cell types and are promising candidates for further development as treatment for SARS-CoV-2.
Journal ArticleDOI
Development of a hybrid alphavirus-SARS-CoV-2 pseudovirion for rapid quantification of neutralization antibodies and antiviral drugs
Brian Hetrick,Linda D. Chilin,Sijia He,Deemah Dabbagh,Farhang Alem,Aarthi Narayanan,Alessandra Luchini,T. Li,Xuefeng Liu,Joshua A. Copeland,A. Pak,Tshaka Cunningham,Lance A. Liotta,Emanuel F. Petricoin,Ali Andalibi,Yuntao Wu +15 more
TL;DR: Ha-CoV-2 as mentioned in this paper is a hybrid alphavirus-SARS CoV2 pseudovirus, which is composed of viral structural proteins (S, M, N, and E) and an RNA genome derived from a fast-expressing vector.
References
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