Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function.
Tzu-Jing Yang,Tzu-Jing Yang,Pei-Yu Yu,Yuan-Chih Chang,Kang-Hao Liang,Hsian-Cheng Tso,Meng-Ru Ho,Wan-Yu Chen,Hsiu-Ting Lin,Han-Chung Wu,Shang-Te Danny Hsu,Shang-Te Danny Hsu +11 more
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TLDR
In this paper, the spike protein of SARS-CoV-2 was analyzed in the apo and ACE2-bound forms and three RBDs were found to be engaged in ACE2 binding.Abstract:
The B.1.1.7 variant of SARS-CoV-2 first detected in the UK harbors amino-acid substitutions and deletions in the spike protein that potentially enhance host angiotensin conversion enzyme 2 (ACE2) receptor binding and viral immune evasion. Here we report cryo-EM structures of the spike protein of B.1.1.7 in the apo and ACE2-bound forms. The apo form showed one or two receptor-binding domains (RBDs) in the open conformation, without populating the fully closed state. All three RBDs were engaged in ACE2 binding. The B.1.1.7-specific A570D mutation introduces a molecular switch that could modulate the opening and closing of the RBD. The N501Y mutation introduces a π-π interaction that enhances RBD binding to ACE2 and abolishes binding of a potent neutralizing antibody (nAb). Cryo-EM also revealed how a cocktail of two nAbs simultaneously bind to all three RBDs, and demonstrated the potency of the nAb cocktail to neutralize different SARS-CoV-2 pseudovirus strains, including B.1.1.7.read more
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Clinical grade ACE2 as a universal agent to block SARS‐CoV‐2 variants
Vanessa Monteil,Brett P. Eaton,Elena Postnikova,Michael Murphy,Benedict Braunsfeld,Ian Crozier,Franz Kricek,Janine Niederhöfer,Alice Schwarzböck,Helene Breid,Stephanie Devignot,Jonas Klingström,Charlotte Thålin,Max J Kellner,Wanda Christ,Sebastian Havervall,Stefan Mereiter,Sylvia Knapp,Anna Sanchez Jimenez,Agnes Bugajska-Schretter,Alexander M. Dohnal,Christine Ruf,Romana Gugenberger,Astrid Hagelkruys,Nuria Montserrat,Ivona Kozieradzki,O. Hasan Ali,Johannes Stadlmann,Michael R. Holbrook,Connie S. Schmaljohn,Chris Oostenbrink,Robert H. Shoemaker,Ali Mirazimi,Gerald Wirnsberger,Josef M. Penninger +34 more
TL;DR: It is reported that all SARS‐CoV‐2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01).
Journal ArticleDOI
Structural Plasticity and Immune Evasion of SARS-CoV-2 Spike Variants
Dibya Ghimire,Yang Han,Maolin Lu +2 more
TL;DR: Recent findings on S-associated virus transmissibility and immune evasion of SARS-CoV-2 VOCs and experimental approaches used to profile these properties are discussed.
Journal ArticleDOI
The Variation of SARS-CoV-2 and Advanced Research on Current Vaccines
TL;DR: The main characteristics of the emerging various variants of SARS-CoV-2, including their distribution, mutations, transmissibility, severity, and susceptibility to immune responses are reviewed, especially the Delta variant and the new emerging Omicron variant.
Posted ContentDOI
Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants
Gerald Wirnsberger,Vanessa Monteil,Brett P Eaton,Elena Postnikova,Michael O. Murphy,Benedict Braunsfeld,Ian Crozier,Franz Kricek,Janine Niederhoefer,Alice Schwarzboeck,Helene Breid,Anna Sanchez Jimenez,Agnes Bugajska-Schretter,Alexander Dohnal,Christine Ruf,Romana Gugenberger,Astrid Hagelkrueys,Nuria Montserrat,Nuria Montserrat,Mike Holbrook,Chris Oostenbrink,Robert H. Shoemaker,Ali Mirazimi,Josef M. Penninger,Josef M. Penninger +24 more
TL;DR: In this article, all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, and Delta, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01).
Journal ArticleDOI
Impact of new variants on SARS-CoV-2 infectivity and neutralization: A molecular assessment of the alterations in the spike-host protein interactions
Mary Hongying Cheng,James Krieger,Anupam Banerjee,Yufei Xiang,Burcak Kaynak,Yi Shi,Moshe Arditi,Ivet Bahar +7 more
TL;DR: In this paper , a comparative analysis of the interactions of Alpha, Beta, Gamma, and Delta variants with cognate molecules (ACE2 and/or furin), neutralizing nanobodies (Nbs), and monoclonal antibodies (mAbs) using in silico methods, in addition to Nb-binding assays is presented.
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
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: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.
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.
Journal ArticleDOI
MolProbity: all-atom structure validation for macromolecular crystallography
Vincent B. Chen,W. Bryan Arendall,Jeffrey J. Headd,Daniel A. Keedy,R.M. Immormino,Gary J. Kapral,Laura Weston Murray,Jane S. Richardson,David S. Richardson +8 more
TL;DR: MolProbity structure validation will diagnose most local errors in macromolecular crystal structures and help to guide their correction.
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