Structure-based design of prefusion-stabilized SARS-CoV-2 spikes
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Abstract
The development of therapeutic antibodies and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on the spike (S) protein that decorates the viral surface. A version of the spike ectodomain that includes two proline substitutions (S-2P) and stabilizes the prefusion conformation has been used to determine high-resolution structures. However, even S-2P is unstable and difficult to produce in mammalian cells. Hsieh et al. characterized many individual and combined structure-guided substitutions and identified a variant, named HexaPro, that retains the prefusion conformation but shows higher expression than S-2P and can also withstand heating and freezing. This version of the protein is likely to be useful in the development of vaccines and diagnostics.
Science , this issue p. 1501
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SciScore for 10.1101/2020.05.30.125484: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources The one-RBD-up reconstruction was subjected to local B-factor sharpening using LocalDeBlur36 and the two-RBD-up reconstruction was sharpened in cryoSPARC. cryoSPARCsuggested: (cryoSPARC, RRID:SCR_016501)Iterative model building and refinement were performed with Coot, Phenix and ISOLDE37–39. Cootsuggested: (Coot, RRID:SCR_014222)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature…
SciScore for 10.1101/2020.05.30.125484: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources The one-RBD-up reconstruction was subjected to local B-factor sharpening using LocalDeBlur36 and the two-RBD-up reconstruction was sharpened in cryoSPARC. cryoSPARCsuggested: (cryoSPARC, RRID:SCR_016501)Iterative model building and refinement were performed with Coot, Phenix and ISOLDE37–39. Cootsuggested: (Coot, RRID:SCR_014222)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
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.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 35. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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