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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Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation.
Joel D. Allen,Himanshi Chawla,Firdaus Samsudin,Lorena Zuzic,Lorena Zuzic,Aishwary Tukaram Shivgan,Aishwary Tukaram Shivgan,Yasunori Watanabe,Wan-ting He,Sean Callaghan,Ge Song,Peter Yong,Philip J. M. Brouwer,Yutong Song,Yongfei Cai,Helen M. E. Duyvesteyn,Tomas Malinauskas,Joeri Kint,Paco Pino,Maria J Wurm,Martin Frank,Bing Chen,Bing Chen,David I. Stuart,Rogier W. Sanders,Rogier W. Sanders,Raiees Andrabi,Dennis R. Burton,Sai Li,Peter J. Bond,Peter J. Bond,Max Crispin +31 more
TL;DR: In this paper, the authors investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
Posted ContentDOI
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,Annemarie Laumaea,Jonathan R. Grover,Liu Lihong,David D. Ho,John R. Mascola,Andrés Finzi,Peter D. Kwong,Scott C. Blanchard,Walther Mothes +22 more
TL;DR: Single-molecule Förster Resonance Energy Transfer imaging is applied to observe conformational dynamics of S on virus particles to inform on mechanisms of S recognition and conformations for immunogen design.
Journal ArticleDOI
Neuropilin-1 assists SARS-CoV-2 infection by stimulating the separation of Spike protein S1 and S2.
Zhenlu Li,Matthias Buck +1 more
TL;DR: In this paper, the authors modeled the association of an Nrp1 protein (consisting of domains a2-b1-b2) with the Spike protein and studied the separation of S2 from the S1 domain.
Journal ArticleDOI
Development of a Clinical MALDI-ToF Mass Spectrometry Assay for SARS-CoV-2: Rational Design and Multi-Disciplinary Team Work
TL;DR: A multifaceted clinical MALDI ToF MS screening test, primarily SARS-CoV-2, with direct application to other future epidemics/pandemics that may arise, and the advantages of the method include ease of sampling, speed of analysis, and much reduced cost of testing.
Posted ContentDOI
Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines
John E. Bowen,Kaitlin R. Sprouse,Alexandra C. Walls,Ignacio Mazzitelli,Jennifer Logue,Nicholas Franko,Kumail Ahmed,Asefa Shariq,Elisabetta Cameroni,Andrea Gori,Alessandra Bandera,Christine M. Posavad,Jennifer M. Dan,Zeli Zhang,Daniela Weiskopf,Alessandro Sette,Shane Crotty,Najeeha Talat Iqbal,Davide Corti,Jorge Geffner,Renata Grifantini,Helen Y. Chu,David Veesler +22 more
TL;DR: The data suggest that although BA.1 and BA.2 evade polyclonal neutralizing antibody responses, current vaccine boosting regimens may provide sufficient protection against Omicron-induced disease.
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