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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A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion.
Alvin Yu,Alexander J. Pak,Peng He,Viviana Monje-Galvan,Lorenzo Casalino,Zied Gaieb,Abigail C. Dommer,Rommie E. Amaro,Gregory A. Voth +8 more
TL;DR: The current status and on-going development of a largely “bottom-up” coarse-grained (CG) model of the SARS-CoV-2 virion is reported and how CG molecular interactions can be derived from all-atom simulations are described.
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Physicochemical properties of SARS-CoV-2 for drug targeting, virus inactivation and attenuation, vaccine formulation and quality control.
TL;DR: The material properties of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its proteins are discussed and standard approaches employed for other viruses and vaccines seem to be feasible including virus inactivation, centrifugation conditions, and the use of adjuvants.
Journal ArticleDOI
The Flexibility of ACE2 in the Context of SARS-CoV-2 Infection.
Emilia P. Barros,Lorenzo Casalino,Zied Gaieb,Abigail C. Dommer,Yuzhang Wang,Lucy Fallon,Lauren Raguette,Kellon A.A. Belfon,Carlos Simmerling,Rommie E. Amaro +9 more
TL;DR: Further structural and functional insights are presented into the role of ACE2 in viral infection that can potentially be exploited for the rational design of effective SARS-CoV-2 therapeutics.
ComponentDOI
Structural and functional analysis of a potent sarbecovirus neutralizing antibody
Dora Pinto,Young-Jun Park,Martina Beltramello,Alexandra C. Walls,M.A. Tortorici,M.A. Tortorici,Siro Bianchi,Stefano Jaconi,Katja Culap,Fabrizia Zatta,Anna De Marco,Alessia Peter,Barbara Guarino,Roberto Spreafico,Elisabetta Cameroni,James Brett Case,Rita Chen,Colin Havenar-Daughton,G. Snell,Amalio Telenti,Herbert W. Virgin,Antonio Lanzavecchia,Michael S. Diamond,Katja Fink,David Veesler,Davide Corti +25 more
TL;DR: Multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of a SARS survivor infected in 2003 are described and it is shown that S309 recognizes a glycan-containing epitope within the sarbecovirus subgenus, without competing with receptor attachment.
Journal ArticleDOI
Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies
Yifan Wang,Caixuan Liu,Chao Zhang,Yanxing Wang,Qin Hong,Shiqi Xu,Zuyang Li,Yong Yang,Zhong-Liang Huang,Yao Cong +9 more
TL;DR: In this paper , the structural basis of the enhanced transmission and altered immune sensitivity of the SARS-CoV-2 Delta variant is uncovered. But the structure of the Delta T478K substitution plays a vital role in stabilizing and reshaping the RBM loop473-490, enhancing interaction with ACE2.
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