Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.
Jun Lan,Jiwan Ge,Jinfang Yu,Sisi Shan,Huan Zhou,Shilong Fan,Qi Zhang,Xuanling Shi,Qisheng Wang,Linqi Zhang,Xinquan Wang +10 more
TLDR
High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.Abstract:
A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1–3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1–3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies. High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS-CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.read more
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Structural basis of receptor recognition by SARS-CoV-2.
Jian Shang,Gang Ye,Ke Shi,Yushun Wan,Chuming Luo,Hideki Aihara,Qibin Geng,Ashley Auerbach,Fang Li +8 more
TL;DR: This study determines the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2 and sheds light on the structural features that increase its binding affinity to ACE2.
Journal ArticleDOI
Extrapulmonary manifestations of COVID-19.
Aakriti Gupta,Aakriti Gupta,Mahesh V. Madhavan,Kartik Sehgal,Kartik Sehgal,Nandini Nair,Shiwani Mahajan,Tejasav S. Sehrawat,Behnood Bikdeli,Behnood Bikdeli,Neha Ahluwalia,John C. Ausiello,Elaine Wan,Daniel E. Freedberg,Ajay J. Kirtane,Sahil A. Parikh,Mathew S. Maurer,Anna S. Nordvig,Domenico Accili,Joan M. Bathon,Sumit Mohan,Kenneth A. Bauer,Kenneth A. Bauer,Martin B. Leon,Harlan M. Krumholz,Nir Uriel,Mandeep R. Mehra,Mitchell S.V. Elkind,Mitchell S.V. Elkind,Gregg W. Stone,Allan Schwartz,David D. Ho,John P. Bilezikian,Donald W. Landry +33 more
TL;DR: The extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 are reviewed to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Journal ArticleDOI
SARS-CoV-2 variants, spike mutations and immune escape.
William T. Harvey,Alessandro M Carabelli,Ben Jackson,Ravindra K. Gupta,E. Thomson,E. Thomson,Ewan M. Harrison,Ewan M. Harrison,Catherine Ludden,Richard Reeve,Andrew Rambaut,Sharon J. Peacock,David Robertson +12 more
TL;DR: A review of the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure is presented in this article.
Journal ArticleDOI
Coronavirus biology and replication: implications for SARS-CoV-2.
TL;DR: The first discoveries that shape the current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle are summarized and relate that to the knowledge of coronavirus biology.
Journal ArticleDOI
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.
Dora Pinto,Young-Jun Park,Martina Beltramello,Alexandra C. Walls,M. Alejandra Tortorici,M. Alejandra Tortorici,Siro Bianchi,Stefano Jaconi,Katja Culap,Fabrizia Zatta,Anna De Marco,Alessia Peter,Barbara Guarino,Roberto Spreafico,Elisabetta Cameroni,James Brett Case,Rita E. Chen,Colin Havenar-Daughton,Gyorgy Snell,Amalio Telenti,Herbert W. Virgin,Antonio Lanzavecchia,Michael S. Diamond,Katja Fink,David Veesler,Davide Corti +25 more
TL;DR: Several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which was identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS- coV) in 2003, and one antibody (named S309) potently neutralization, which may limit the emergence of neutralization-escape mutants.
References
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Structural Basis of Neutralization by a Human Anti-severe Acute Respiratory Syndrome Spike Protein Antibody, 80R
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Aquarium: an automatic data-processing and experiment information management system for biological macromolecular crystallography beamlines
Feng Yu,Qisheng Wang,Minjun Li,Huan Zhou,Ke Liu,Kunhao Zhang,Zhijun Wang,Qin Xu,Chuanyan Xu,Qiangyan Pan,Jianhua He +10 more
TL;DR: Aquarium is an automatic data processing and experiment information management system designed for synchrotron radiation source MX beamlines that will automatically process data sets from data reduction to model building if the anomalous signal is available.
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