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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SARS-CoV-2 mutations acquired in mink reduce antibody-mediated neutralization.
Markus Hoffmann,Lu Zhang,Nadine Krüger,Luise Graichen,Hannah Kleine-Weber,Heike Hofmann-Winkler,Amy Kempf,Stefan Nessler,Joachim Riggert,Martin Sebastian Winkler,Sebastian R. Schulz,Hans-Martin Jäck,Stefan Pöhlmann +12 more
TL;DR: In this paper, the authors reported that mutations frequently found in the spike protein of SARS-CoV-2 from mink are mostly compatible with efficient entry into human cells and its inhibition by soluble angiotensin-converting enzyme 2 (ACE2).
Posted ContentDOI
Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants
Yongfei Cai,Yongfei Cai,Jun Zhang,Jun Zhang,Tianshu Xiao,Tianshu Xiao,Christy L. Lavine,Shaun Rawson,Hanqin Peng,Haisun Zhu,Krishna Anand,Pei Tong,Avneesh Gautam,Shen Lu,Sarah M. Sterling,Richard M. Walsh,Sophia Rits-Volloch,Jianming Lu,Duane R. Wesemann,Wei Yang,Michael S. Seaman,Bing Chen,Bing Chen +22 more
TL;DR: In this article, the full-length spike (S) trimers of the B.1.7 and B.351 variants of SARS-CoV-2 have been analyzed.
Posted ContentDOI
SARS-CoV-2 variants B.1.351 and B.1.1.248: Escape from therapeutic antibodies and antibodies induced by infection and vaccination
Markus Hoffmann,Markus Hoffmann,Prerna Arora,Prerna Arora,Ruediger Gross,Alina Seidel,Bojan Hoernich,Alexander S. Hahn,Nadine Krueger,Luise Graichen,Heike Hofmann-Winkler,Amy Kempf,Amy Kempf,Martin Sebastian Winkler,Sebastian R. Schulz,Hans-Martin Jaeck,Bernd Jahrsdoerfer,Hubert Schrezenmeier,Martin Mueller,Alexander Kleger,Jan Muench,Stefan Poehlmann,Stefan Poehlmann +22 more
TL;DR: In this article, the authors show that SARS-CoV-2 may escape antibody responses, which has important implications for efforts to contain the pandemic, and they show that entry of UK, South Africa, and Brazil variants into human cells is susceptible to blockade by entry inhibitors and that the South Africa and Brazil variant was partially or fully resistant to antibodies used for COVID-19 treatment and was less efficiently inhibited by serum or plasma from convalescent or BNT162b2 vaccinated individuals.
Journal ArticleDOI
Analysis of ACE2 genetic variants in 131 Italian SARS-CoV-2-positive patients.
Antonio Novelli,Michela Biancolella,Paola Borgiani,Dario Cocciadiferro,Vito Luigi Colona,Maria Rosaria D'Apice,Paola Rogliani,Salvatore Zaffina,Francesca Leonardis,Andrea Campana,Massimiliano Raponi,Massimo Andreoni,Sandro Grelli,Giuseppe Novelli +13 more
TL;DR: There is no strong evidence, in this cohort, of consistent association of ACE2 variants with COVID-19 severity, and it might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of the ACE2 gene, known to play a role in regulation of the gene activity.
Journal ArticleDOI
Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis
Natalia G. Herrera,Nicholas C. Morano,A. Celikgil,George I. Georgiev,Ryan J. Malonis,James H. Lee,Karen Tong,Olivia Vergnolle,Aldo Massimi,Laura Y. Yen,Alex J. Noble,Mykhailo Kopylov,Jeffrey B. Bonanno,Sarah C. Garrett-Thomson,David B. Hayes,Robert H. Bortz,Ariel S. Wirchnianski,Catalina Florez,Catalina Florez,Ethan Laudermilch,Denise Haslwanter,J. Maximilian Fels,M. Eugenia Dieterle,Rohit K. Jangra,Jason Barnhill,Amanda Mengotto,Duncan Kimmel,Johanna P. Daily,Liise Anne Pirofski,Kartik Chandran,Michael Brenowitz,Scott J. Garforth,Edward T. Eng,Jonathan R. Lai,S.C. Almo +34 more
TL;DR: In this article, the authors evaluated the expression and purification of two previously reported S protein constructs in Expi293F and ExpiCHO-S cells, two different cell lines selected for increased protein expression.
References
More filters
Journal ArticleDOI
UCSF Chimera--a visualization system for exploratory research and analysis.
Eric F. Pettersen,Thomas D. Goddard,Conrad C. Huang,Gregory S. Couch,Daniel M. Greenblatt,Elaine C. Meng,Thomas E. Ferrin +6 more
TL;DR: Two unusual extensions are presented: Multiscale, which adds the ability to visualize large‐scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales.
Journal ArticleDOI
Features and development of Coot.
TL;DR: Coot is a molecular-graphics program designed to assist in the building of protein and other macromolecular models and the current state of development and available features are presented.
Journal ArticleDOI
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Journal ArticleDOI
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
Book ChapterDOI
Phenix - a comprehensive python-based system for macromolecular structure solution
Paul D. Adams,Paul D. Adams,Pavel V. Afonine,Gábor Bunkóczi,Vincent B. Chen,Ian W. Davis,Nathaniel Echols,Jeffrey J. Headd,Li-Wei Hung,Gary J. Kapral,Ralf W. Grosse-Kunstleve,Airlie J. McCoy,Nigel W. Moriarty,Robert D. Oeffner,Randy J. Read,David S. Richardson,Jane S. Richardson,Thomas C. Terwilliger,Peter H. Zwart +18 more
TL;DR: PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures.
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