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
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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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Journal ArticleDOI
Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization.
Delphine Planas,David Veyer,Artem Baidaliuk,Isabelle Staropoli,Florence Guivel-Benhassine,Maaran Michael Rajah,Maaran Michael Rajah,Cyril Planchais,Françoise Porrot,Nicolas Robillard,Julien Puech,Matthieu Prot,Floriane Gallais,Pierre Gantner,Aurélie Velay,Julien Le Guen,Najiby Kassis-Chikhani,Dhiaeddine Edriss,Laurent Bélec,Aymeric Sève,Laura Courtellemont,Hélène Péré,Laurent Hocqueloux,Samira Fafi-Kremer,Thierry Prazuck,Hugo Mouquet,Timothée Bruel,Etienne Simon-Loriere,Félix A. Rey,Olivier Schwartz +29 more
TL;DR: In this paper, an infectious strain of the SARS-CoV-2 Delta variant was isolated from an individual with COVID-19 who had returned to France from India.
Journal ArticleDOI
Mechanisms of SARS-CoV-2 entry into cells.
TL;DR: In this article, structural and cellular foundations for understanding the multistep SARS-CoV-2 entry process, including S protein synthesis, S protein structure, conformational transitions necessary for association of the spike (S) protein with ACE2, engagement of the receptor-binding domain of the S protein with ACS, proteolytic activation of S protein, endocytosis and membrane fusion are provided.
Journal ArticleDOI
Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies.
Allison J. Greaney,Allison J. Greaney,Andrea N. Loes,Andrea N. Loes,Katharine H.D. Crawford,Katharine H.D. Crawford,Tyler N. Starr,Tyler N. Starr,Keara D. Malone,Helen Y. Chu,Jesse D. Bloom,Jesse D. Bloom +11 more
TL;DR: In this article, the authors map how convalescent plasma antibodies are impacted by all mutations to the spike's receptor-binding domain (RBD), the main target of plasma neutralizing activity.
Journal ArticleDOI
Structures and distributions of SARS-CoV-2 spike proteins on intact virions.
Zunlong Ke,Joaquín Otón,Kun Qu,Mirko Cortese,Vojtech Zila,Lesley McKeane,Takanori Nakane,Jasenko Zivanov,Christopher J. Neufeldt,Berati Cerikan,John M. Lu,Julia Peukes,Xiaoli Xiong,Hans-Georg Kräusslich,Sjors H.W. Scheres,Ralf Bartenschlager,Ralf Bartenschlager,John A. G. Briggs +17 more
TL;DR: Cryo-electron microscopy and tomography is applied to image intact SARS-CoV-2 virions, determining the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface and providing a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.
Journal ArticleDOI
SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies.
Markus Hoffmann,Markus Hoffmann,Prerna Arora,Prerna Arora,Rüdiger Groß,Alina Seidel,Bojan F. Hörnich,Alexander S. Hahn,Nadine Krüger,Luise Graichen,Heike Hofmann-Winkler,Amy Kempf,Amy Kempf,Martin Sebastian Winkler,Sebastian R. Schulz,Hans-Martin Jäck,Bernd Jahrsdörfer,Bernd Jahrsdörfer,Hubert Schrezenmeier,Hubert Schrezenmeier,Martin Müller,Alexander Kleger,Jan Münch,Stefan Pöhlmann,Stefan Pöhlmann +24 more
TL;DR: In this article, the authors show that SARS-CoV-2/COVID-19 variants B.1.7 (UK), B.351 (South Africa), and P.1 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies.
References
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Book ChapterDOI
Structural insights into coronavirus entry
TL;DR: The understanding of the infection mechanism used by coronaviruses derived from recent structural and biochemical studies is reviewed.
Posted ContentDOI
Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications
Fan Wu,Aojie Wang,Liu Mei,Qimin Wang,Jun Chen,Shuai Xia,Yun Ling,Yuling Zhang,Jingna Xun,Lu Lu,Shibo Jiang,Hongzhou Lu,Yumei Wen,Jinghe Huang +13 more
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Journal ArticleDOI
Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein
Jean K. Millet,Gary R. Whittaker +1 more
TL;DR: It is shown that MERS-CoV has evolved an unusual two-step furin activation for fusion, suggestive of a role during the process of emergence into the human population, and may explain the polytropic nature of the virus.
Posted ContentDOI
The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity
Lizhou Zhang,Cody B. Jackson,Huihui Mou,Amrita Ojha,Erumbi S. Rangarajan,Tina Izard,Michael Farzan,Hyeryunc Choe +7 more
TL;DR: Results show SG614 is more stable than SD614, consistent with epidemiological data suggesting that viruses with SG614 transmit more efficiently, and the pseudoviruses containing these S proteins were neutralized with comparable efficiencies by convalescent plasma.
Journal ArticleDOI
Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion
Alexandra C. Walls,M. Alejandra Tortorici,M. Alejandra Tortorici,Joost Snijder,Xiaoli Xiong,Berend Jan Bosch,Félix A. Rey,Félix A. Rey,David Veesler +8 more
TL;DR: The cryoEM structure of an S glycoprotein in the postfusion state, showing large-scale rearrangements compared with the prefusion trimer, provides a structural framework for understanding antibody neutralization and for engineering vaccines against this medically important virus family.
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