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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Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates.
Linling He,Xiaohe Lin,Ying Wang,Ciril Abraham,Cindy Sou,Timothy Ngo,Yi Zhang,Ian A. Wilson,Jiang Zhu +8 more
TL;DR: In this article, the authors combined antigen optimization and nanoparticle display to develop vaccine candidates for SARS-CoV-2, which provided an effective tool to combat the COVID-19 pandemic.
Journal ArticleDOI
Cryo-EM structure of the SARS-CoV-2 Omicron spike
Gabriele Cerutti,Yicheng Guo,Lihong Liu,Liyuan Liu,Zhening Zhang,Yang Luo,Yiming Huang,Harris H. Wang,David D. Ho,Zizhang Sheng,Lawrence Shapiro +10 more
TL;DR: In this paper , a 3.1 Å-resolution cryoelectron microscopy (cryo-EM) structure of the Omicron spike protein ectodomain was presented, showing a spike that is exclusively in the 1-RBD-up conformation with high mobility of RBD.
Journal ArticleDOI
Omicron variant Spike-specific antibody binding and Fc activity is preserved in recipients of mRNA or inactivated COVID-19 vaccines
Yannic C. Bartsch,Xinzhao Tong,Jaewon Kang,Maria Jose Avendano,Eileen F. Serrano,Tamara García-Salum,Catalina Pardo-Roa,Arnoldo Riquelme,Yongfei Cai,Isabella Renzi,Guillaume Stewart-Jones,Bing Chen,Rafael A. Medina,Galit Alter +13 more
TL;DR: It is shown that vaccination with BNT162b2, mRNA-1273, or CoronaVac induced antibodies that were still capable of binding to the Omicron variant Spike protein were also able to elicit Fc-mediated effector functions, suggesting that they may play a role in controlling disease after infection with the O micron variant.
Journal ArticleDOI
Molecular Simulations and Network Modeling Reveal an Allosteric Signaling in the SARS-CoV-2 Spike Proteins
TL;DR: Evidence is presented that the SARS-CoV-2 spike protein can function as an allosteric regulatory engine that fluctuates between dynamically distinct functional states and can control the dynamic switching between functional conformational states associated with virus entry to the host receptor.
Journal ArticleDOI
Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections.
Chao Zhang,Yifan Wang,Yuanfei Zhu,Caixuan Liu,Chenjian Gu,Shiqi Xu,Yalei Wang,Yu Zhou,Yanxing Wang,W. Han,Xiaoyu Hong,Yong Yang,Xueyang Zhang,Tingfeng Wang,Cong Xu,Qin Hong,S. Wang,Qiaoyu Zhao,Weihua Qiao,Jinkai Zang,Liangliang Kong,Fangfang Wang,Haikun Wang,Di Qu,Dimitri Lavillette,Hong Tang,Qiang Deng,Youhua Xie,Yao Cong,Zhong Huang +29 more
TL;DR: In this paper, the authors identify and characterize two mouse-derived monoclonal antibodies against SARS-CoV-2 spike protein that target different epitopes in RBD and block the interaction S/ACE2 and show that a formulated humanized version of the 2H2/3C1 cocktail exhibits prophylaxis and therapeutic antiviral effects in an hACE2-adenovector expressed mouse model.
References
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