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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Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets.
Rory D. de Vries,Katharina S. Schmitz,Francesca T. Bovier,Francesca T. Bovier,Camilla Predella,Camilla Predella,Jonathan Khao,Danny Noack,Bart L. Haagmans,Sander Herfst,Kyle Stearns,Jennifer Drew-Bear,Sudipta Biswas,Barry Rockx,Gaël McGill,N. Valerio Dorrello,Samuel H. Gellman,Christopher A. Alabi,Rik L. de Swart,Anne Moscona,Matteo Porotto,Matteo Porotto +21 more
TL;DR: In this article, the authors designed lipopeptide fusion inhibitors that block this critical first step of infection and, on the basis of in vitro efficacy and in vivo biodistribution, selected a dimeric form for evaluation in an animal model.
Journal ArticleDOI
Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.
Xing Zhu,Dhiraj Mannar,Shanti Swaroop Srivastava,Alison M. Berezuk,Jean-Philippe Demers,James W. Saville,Karoline Leopold,Wei Li,Dimiter S. Dimitrov,Katharine Tuttle,Steven Zhou,Sagar Chittori,Sriram Subramaniam +12 more
TL;DR: In this article, a 2.9-A resolution structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains was presented, showing that Y501 inserted into a cavity at the binding interface near Y41 of ACE2.
Journal ArticleDOI
Structure-guided covalent stabilization of coronavirus spike glycoprotein trimers in the closed conformation.
TL;DR: The design of a construct corresponding to the prefusion SARS-CoV-2 S ectodomain trimer is reported, covalently stabilized by a disulfide bond in the closed conformation, and might become an important tool for structural biology, serology, vaccine design and immunology studies.
Journal ArticleDOI
Liquid-liquid phase separation in human health and diseases.
Bin Wang,Bin Wang,Zhang Lei,Tong Dai,Ziran Qin,Ziran Qin,Huasong Lu,Long Zhang,Fangfang Zhou +8 more
TL;DR: A review of liquid-liquid phase separation (LLPS) in eukaryotic cells can be found in this paper, where the authors describe the current understanding of LLPS and summarize its physiological functions.
Journal ArticleDOI
Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles.
Maolin Lu,Pradeep D. Uchil,Wenwei Li,Desheng Zheng,Daniel S. Terry,Jason Gorman,Wei Shi,Baoshan Zhang,Tongqing Zhou,Shilei Ding,Romain Gasser,Jérémie Prévost,Guillaume Beaudoin-Bussières,Sai Priya Anand,Sai Priya Anand,Annemarie Laumaea,Jonathan R. Grover,Lihong Liu,David D. Ho,John R. Mascola,Andrés Finzi,Andrés Finzi,Peter D. Kwong,Scott C. Blanchard,Walther Mothes +24 more
TL;DR: Conformational preferences observed upon expsoure to convalescent plasma or antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to the receptor-binding domain (RBD) or allosteric interference with conformational changes required for entry.
References
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