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
Citations
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Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions.
Yingjie Wang,Meiyi Liu,Jiali Gao +2 more
TL;DR: Analysis of the dynamic trajectories reveals that the binding interface consists of a primarily hydrophobic region and a delicate hydrogen-bonding network in the 2019 novel coronavirus.
Posted ContentDOI
Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding.
Tyler N. Starr,Allison J. Greaney,Allison J. Greaney,Sarah K Hilton,Sarah K Hilton,Katharine H.D. Crawford,Katharine H.D. Crawford,Mary Jane Navarro,John E. Bowen,M. Alejandra Tortorici,Alexandra C. Walls,David Veesler,Jesse D. Bloom,Jesse D. Bloom,Jesse D. Bloom +14 more
TL;DR: An interactive visualization and open analysis pipeline is presented to facilitate use of the dataset for vaccine design and functional annotation of mutations observed during viral surveillance.
Journal ArticleDOI
COVID-19 and the elderly: insights into pathogenesis and clinical decision-making.
Fabio Perrotta,Graziamaria Corbi,Grazia Mazzeo,Matilde Boccia,Luigi Aronne,Vito D'Agnano,Klara Komici,Gennaro Mazzarella,Roberto Parrella,Andrea Bianco +9 more
TL;DR: The elderly may represent a specific cluster of high-risk patients for developing COVID-19 with rapidly progressive clinical deterioration and early diagnosis and individualized therapeutic management should be developed for elderly subjects based on personal medical history and polypharmacotherapy.
Journal ArticleDOI
The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA.
Jasmine Cubuk,Jhullian J. Alston,J. Jeremías Incicco,Sukrit Singh,Melissa D. Stuchell-Brereton,Michael D. Ward,Maxwell I. Zimmerman,Neha Vithani,Daniel Griffith,Jason A. Wagoner,Gregory R. Bowman,Kathleen B. Hall,Andrea Soranno,Alex S. Holehouse +13 more
TL;DR: The SARS-CoV-2 nucleocapsid (N) protein is an abundant RNA-binding protein critical for viral genome packaging, yet the molecular details that underlie this process are poorly understood as discussed by the authors.
Journal ArticleDOI
The antigenic anatomy of SARS-CoV-2 receptor binding domain.
Wanwisa Dejnirattisai,D. Zhou,Helen M. Ginn,Helen M. E. Duyvesteyn,Piyada Supasa,James Brett Case,Yuguang Zhao,Thomas S. Walter,Alexander J. Mentzer,Chang Liu,Beibei Wang,Guido C. Paesen,J Slon-Campos,Cesar Lopez-Camacho,Natasha M. Kafai,Adam L. Bailey,Rita E. Chen,Baoling Ying,Craig Thompson,Jai S Bolton,Alex Fyfe,Sunetra Gupta,Tiong Kit Tan,Javier Gilbert-Jaramillo,William James,Michael L. Knight,Miles W. Carroll,Donal T. Skelly,Christina Dold,Yanchun Peng,R Levin,Tao Dong,Andrew J. Pollard,Julian C. Knight,Paul Klenerman,Nigel J. Temperton,David R. Hall,Mark A. Williams,Neil G. Paterson,Felicity K.R. Bertram,C. Alistair Siebert,Daniel K. Clare,Andy G. Howe,Julika Radecke,Yun Song,Alain Townsend,Kuan-Ying A. Huang,Elizabeth E. Fry,Juthathip Mongkolsapaya,Juthathip Mongkolsapaya,Michael S. Diamond,Jingshan Ren,David I. Stuart,Gavin R. Screaton +53 more
TL;DR: In this paper, the authors identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD) and devise a competition data-driven method to map RBD binding sites.
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