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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The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism
Brian J. Willett,Joe Grove,Oscar A. MacLean,Craig Wilkie,Nicola S Logan,Giuditta De Lorenzo,Wilhelm Furnon,Samuel Scott,M. Manali,Agnieszka M. Szemiel,Shirin Ashraf,Elen Vink,William T. Harvey,Chris Davis,Richard J. Orton,Joseph Hughes,P Holland,Vanessa K. A. Silva,David J Pascall,Kathryn Puxty,Ana da Silva Filipe,Gonzalo Yebra,Sharif Shaaban Muhammad Shaaban,Matthew T. G. Holden,Rute Maria Pinto,Rory Gunson,Kate Templeton,Pablo R. Murcia,Arvind H. Patel,John Haughney,David Robertson,Massimo Palmarini,Surajit Ray,E. Thomson +33 more
TL;DR: It is shown that immunity from natural infection (without vaccination) is more protective than two doses of vaccine but inferior to three doses, and fundamental changes in the Omicron entry process in vitro, towards TMPRSS2-independent fusion, representing a major shift in the replication properties of SARS-CoV-2.
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Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies
Allison J. Greaney,Allison J. Greaney,Andrea N. Loes,Andrea N. Loes,Katharine H.D. Crawford,Katharine H.D. Crawford,Tyler N. Starr,Tyler N. Starr,Keara D. Malone,Helen Y. Chu,Jesse D. Bloom,Jesse D. Bloom +11 more
TL;DR: In this article, the authors map how convalescent serum antibodies are impacted by all mutations to the spike9s receptor-binding domain (RBD), the main target of serum neutralizing activity.
Journal ArticleDOI
Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein.
TL;DR: A cryo-EM structure of SARS-CoV post-fusion S2 trimer is reported, providing insights into the fusion mechanism that could be useful for therapeutic development against coronaviruses.
Journal ArticleDOI
Serum Proteomics in COVID-19 Patients: Altered Coagulation and Complement Status as a Function of IL-6 Level.
Angelo D'Alessandro,Tiffany Thomas,Monika Dzieciatkowska,Ryan C. Hill,Richard O. Francis,Krystalyn E. Hudson,James C. Zimring,Eldad A. Hod,Steven L. Spitalnik,Kirk C. Hansen +9 more
TL;DR: This study provides the first proteomics analysis of sera from COVID-19 patients, stratified by circulating levels of IL-6, and correlated to markers of inflammation and renal function, and identified significant dysregulation in serum levels of various coagulation factors, accompanied by increased levels of antifibrinolytic components, including several serine protease inhibitors (SERPINs).
Journal ArticleDOI
Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity? Insights from All-Atom Simulations.
TL;DR: Multi-microsecond-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 toward ACE2 as compared to SARS -CoV, supplying a minute per-residue contact map underlining its stunningly high infectivity.
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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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