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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In silico mutagenesis of human ACE2 with S protein and translational efficiency explain SARS-CoV-2 infectivity in different species.
TL;DR: Human are the top species in which SARS-CoV-2 is both efficiently translated as well as optimally interacting with ACE2 and translational efficiency explains animal infectivity, and some viral mutations that increase affinity for hACE and some hACE2 variants affecting ACE2 stability and virus binding are found.
Journal ArticleDOI
Clinical features and risk factors of COVID-19-associated liver injury and function: A retrospective analysis of 830 cases.
TL;DR: Investigation of the changes of parameters (ALT, AST) in LI and the risk factors for LI in a cohort of 830 COVID-19 patients found CRP levels > 1.0 mg/dL, lymphocyte proportion < 20%, AST/ALT ratio < 1, and triglyceride levels >1.7 mol/L are potential risk factors.
Journal ArticleDOI
Quinazoline-Schiff base conjugates: in silico study and ADMET predictions as multi-target inhibitors of coronavirus (SARS-CoV-2) proteins
TL;DR: This study provides an insight into the potential bindings between quinazoline-Schiff base conjugates and SARS-CoV-2 proteins, including spike glycoprotein (SGp), main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), to offer an opportunity to find an effective therapy.
Journal ArticleDOI
Molecular recognition of SARS-CoV-2 spike glycoprotein: quantum chemical hot spot and epitope analyses
TL;DR: This study applied the fragment molecular orbital (FMO) method to characterize the SARS-CoV-2 S-protein binding interactions with not only ACE2 but also the B38 Fab antibody involved in ACE2-inhibitory binding, and identified amino acid residues critical for molecular recognition between S- protein and ACE2 or B 38 Fab antibody.
Journal ArticleDOI
A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0.
Silvia Gervasoni,Giulio Vistoli,Carmine Talarico,Candida Manelfi,Andrea R. Beccari,Gabriel Studer,Gabriel Studer,Gerardo Tauriello,Gerardo Tauriello,Andrew Waterhouse,Andrew Waterhouse,Torsten Schwede,Torsten Schwede,Alessandro Pedretti +13 more
TL;DR: The presented strategy for pocket mapping based on the combination of pocket and docking searches proved successful in precisely characterizing a set of SARS-CoV-2 druggable binding pockets including both orthosteric and allosteric sites, which are clearly amenable for virtual screening campaigns and drug repurposing studies.
References
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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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