Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants
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Abstract
The surge of COVID-19 infection cases is spurred by emerging SARS-CoV-2 variants such as B.1.617. Here we report 38 cryo-EM structures, corresponding to the spike protein of the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Kappa (B.1.617.1) variants in different functional states with and without its receptor, ACE2. Mutations on the N-terminal domain not only alter the conformation of the highly antigenic supersite of the Delta variant, but also remodel the glycan shield by deleting or adding N-glycans of the Delta and Gamma variants, respectively. Substantially enhanced ACE2 binding was observed for all variants, whose mutations on the receptor binding domain modulate the electrostatics of the binding interfaces. Despite their abilities to escape host immunity, all variants can be potently neutralized by three unique antibodies.
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SciScore for 10.1101/2021.09.12.459978: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The plasmids of all S variants were transiently expressed in HEK293 Freestyle cells with polyethylenimine. HEK293suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)Briefly, transient expression of recombinant ACE2 was achieved in Expi293 cells. Expi293suggested: RRID:CVCL_D615)Pseudovirus neutralization assay: The pseudovirus neutralization assays were performed using 293T cells overexpressing ACE2 as described previously32. 293Tsuggested: NoneRecombinant DNA Sentences Resources Expression and purification of S-Beta, Gamma, Delta, and Kappa variants: The codon-optimized DNA … SciScore for 10.1101/2021.09.12.459978: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The plasmids of all S variants were transiently expressed in HEK293 Freestyle cells with polyethylenimine. HEK293suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)Briefly, transient expression of recombinant ACE2 was achieved in Expi293 cells. Expi293suggested: RRID:CVCL_D615)Pseudovirus neutralization assay: The pseudovirus neutralization assays were performed using 293T cells overexpressing ACE2 as described previously32. 293Tsuggested: NoneRecombinant DNA Sentences Resources Expression and purification of S-Beta, Gamma, Delta, and Kappa variants: The codon-optimized DNA sequences corresponding to residues 1-1209 of S-Beta, Gamma, Delta, and Kappa variants were individually cloned into the mammalian expression vector pcDNA3.4-TOPO (Invitrogen, U. S. A.), which contains a foldon trimerization domain based on phage T4 fibritin followed by a c-Myc epitope and a hexa-repeat histidine tag as previously described32,42. pcDNA3.4-TOPOsuggested: NoneSoftware and Algorithms Sentences Resources Data processing was accomplished by using cryoSPARC v2.14. cryoSPARCsuggested: (cryoSPARC, RRID:SCR_016501)Data acquisition was performed on a 300 keV Titan Krios microscope equipped with a Gatan K3 direct electron detector (Gatan, U. S. A.) in a super-resolution mode using EPU v2.10 software (ThermoFisher Scientific, U. S. A.). EPUsuggested: NoneImage processing and 3D reconstruction: All 2x binned super-resolution movie files were analyzed by Relion-3.044 with dose-weighting and 5×5 patch-based alignment using MotionCor2 (v1.2.6)45. MotionCor2suggested: (MotionCor2, RRID:SCR_016499)Structural visualization and rendering of structural representations were accomplished by using UCSF-ChimeraX and Pymol 2.4.1 (Schrodinger Inc. U. S. A.) Pymolsuggested: (PyMOL, RRID:SCR_000305)IC50 was determined by a four-parameter logistic regression using GraphPad Prism 9 (GraphPad, U. S. A.). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
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