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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Potently neutralizing and protective human antibodies against SARS-CoV-2.
Seth J. Zost,Pavlo Gilchuk,James Brett Case,Elad Binshtein,Rita E. Chen,Joseph P. Nkolola,Alexandra Schäfer,Joseph X. Reidy,Andrew Trivette,Rachel S. Nargi,Rachel E. Sutton,Naveenchandra Suryadevara,David R. Martinez,Lauren E. Williamson,Elaine C. Chen,Taylor Jones,Samuel Day,Luke Myers,Ahmed O. Hassan,Natasha M. Kafai,Emma S. Winkler,Julie M. Fox,Swathi Shrihari,Benjamin K. Mueller,Jens Meiler,Jens Meiler,Abishek Chandrashekar,Noe B. Mercado,James J. Steinhardt,Kuishu Ren,Yueh-Ming Loo,Nicole L. Kallewaard,Broc T. McCune,Shamus P. Keeler,Michael J. Holtzman,Dan H. Barouch,Lisa E. Gralinski,Ralph S. Baric,Larissa B. Thackray,Michael S. Diamond,Robert H. Carnahan,James E. Crowe +41 more
TL;DR: An analysis identifies human monoclonal antibodies that potently neutralize wild-type SARS-CoV-2 and protect animals from disease, including two that synergize in a cocktail, suggesting that these could be candidates for use as therapeutic agents for the treatment of COVID-19 in humans.
Journal ArticleDOI
Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition.
Allison J. Greaney,Allison J. Greaney,Tyler N. Starr,Pavlo Gilchuk,Seth J. Zost,Elad Binshtein,Andrea N. Loes,Andrea N. Loes,Sarah K Hilton,John Huddleston,Rachel Eguia,Katharine H.D. Crawford,Katharine H.D. Crawford,Adam S. Dingens,Rachel S. Nargi,Rachel E. Sutton,Naveenchandra Suryadevara,Paul W. Rothlauf,Paul W. Rothlauf,Zhuoming Liu,Sean P. J. Whelan,Robert H. Carnahan,Robert H. Carnahan,James E. Crowe,James E. Crowe,Jesse D. Bloom,Jesse D. Bloom,Jesse D. Bloom +27 more
TL;DR: A deep mutational scanning method is described to map how all amino-acid mutations in the RBD affect antibody binding, and this method is applied to 10 human monoclonal antibodies to enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.
Journal ArticleDOI
SARS-CoV-2 (COVID-19) by the numbers.
TL;DR: This paper provided a one-stop, curated graphical source for the key numbers about the SARS-CoV-2 virus that is responsible for the COVID-19 pandemic.
Journal ArticleDOI
SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity
Lizhou Zhang,Cody B. Jackson,Huihui Mou,Amrita Ojha,Haiyong Peng,Brian D. Quinlan,Erumbi S. Rangarajan,Andi Pan,Abigail Vanderheiden,Mehul S. Suthar,Wenhui Li,Tina Izard,Christoph Rader,Michael Farzan,Hyeryun Choe +14 more
TL;DR: Pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than those with SD614, and D614G may increase infectivity by assembling more functional S protein into the virion.
Journal ArticleDOI
Viral targets for vaccines against COVID-19.
Lianpan Dai,George F. Gao +1 more
TL;DR: In this article, the authors discuss which viral elements are used in COVID-19 vaccine candidates, why they might act as good targets for the immune system and the implications for protective immunity.
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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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