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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SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2.
Fatima Amanat,Mahima Thapa,Tinting Lei,Shaza M. Sayed Ahmed,Daniel C. Adelsberg,Juan Manuel Carreño,Shirin Strohmeier,Aaron J. Schmitz,Sarah Zafar,Julian Q. Zhou,Willemijn Rijnink,Hala Alshammary,Nicholas Borcherding,Ana Gonzalez Reiche,Komal Srivastava,Emilia Mia Sordillo,Harm van Bakel,Bulbul Ahmed,Deena R. Altman,Angela Amoako,Mahmoud Awawda,Katherine Beach,Carolina Bermúdez-González,Rachel Chernet,Lily Q. Eaker,Shelcie Fabre,Emily D. Ferreri,Daniel L. Floda,Charles R Gleason,Giulio Kleiner,Denise Jurczyszak,Julia C. Matthews,Wanni A. Mendez,Lubbertus C. F. Mulder,Jose Polanco,Kayla T. Russo,Ashley Beathrese T. Salimbangon,Miti Saksena,Amber S. Shin,Levy A. Sominsky,Sayahi Suthakaran,Ania Wajnberg,Jackson S. Turner,Goran Bajic,Viviana Simon,Ali H. Ellebedy,Florian Krammer +46 more
TL;DR: In this article, the authors profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine.
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Higher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities.
TL;DR: It is demonstrated that biological sex is a fundamental variable of critical relevance to the authors' mechanistic understanding of SARS-CoV-2 infection and the pursuit of effective COVID-19 preventative and therapeutic strategies.
Journal ArticleDOI
ACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19.
Mengzhen Dong,Jie Zhang,Xuefeng Ma,Jie Tan,Lizhen Chen,Shousheng Liu,Yongning Xin,Likun Zhuang +7 more
TL;DR: It seems that there is a potential involvement of ACE2 and TMPRSS2 expressions in the virus infection of extrapulmonary organs and the manifestation of symptoms related to these organs in patients with COVID-19.
Journal ArticleDOI
Domains and Functions of Spike Protein in Sars-Cov-2 in the Context of Vaccine Design.
TL;DR: In this article, the authors dissected the various domains of SARS-2-S and their functions through a variety of different experimental and theoretical approaches to build a foundation for a comprehensive mechanistic understanding of how SARS 2-S works to mediating cell entry and subsequent cell-to-cell transmission.
Posted ContentDOI
Syncytia formation by SARS-CoV-2 infected cells
Julian Buchrieser,Julian Buchrieser,Jérémy Dufloo,Jérémy Dufloo,Mathieu Hubert,Mathieu Hubert,Blandine Monel,Blandine Monel,Delphine Planas,Delphine Planas,Maaran Michael Rajah,Maaran Michael Rajah,Cyril Planchais,Françoise Porrot,Françoise Porrot,Florence Guivel-Benhassine,Florence Guivel-Benhassine,Sylvie van der Werf,Sylvie van der Werf,Nicoletta Casartelli,Nicoletta Casartelli,Hugo Mouquet,Timothée Bruel,Timothée Bruel,Olivier Schwartz,Olivier Schwartz +25 more
TL;DR: It is shown that SARS-CoV-2 infected cells express the viral Spike protein at their surface and fuse with ACE2-positive neighbouring cells, which facilitates syncytia formation and thwarts the antiviral effect of IFITMs.
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TL;DR: A description is given of Phaser-2.1: software for phasing macromolecular crystal structures by molecular replacement and single-wavelength anomalous dispersion phasing.
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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.
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