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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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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The role of the transmembrane and of the intraviral domain of glycoproteins in membrane fusion of enveloped viruses.
Britta Schroth-Diez,Kai Ludwig,Kai Ludwig,Bolormaa Baljinnyam,Christine Kozerski,Christine Kozerski,Qiang Huang,Andreas Herrmann +7 more
TL;DR: The article will focus on the role of both sequences in the fusion process, with some exceptions, the intraviral domain seems to be not required for fusion activity of viral fusion proteins.
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