Discovery of human ACE2 variants with altered recognition by the SARS-CoV-2 spike protein
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Abstract
Understanding how human ACE2 genetic variants differ in their recognition by SARS-CoV-2 can facilitate the leveraging of ACE2 as an axis for treating and preventing COVID-19. In this work, we experimentally interrogate thousands of ACE2 mutants to identify over one hundred human single-nucleotide variants (SNVs) that are likely to have altered recognition by the virus, and make the complementary discovery that ACE2 residues distant from the spike interface influence the ACE2-spike interaction. These findings illuminate new links between ACE2 sequence and spike recognition, and could find substantial utility in further fundamental research that augments epidemiological analyses and clinical trial design in the contexts of both existing strains of SARS-CoV-2 and novel variants that may arise in the future.
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SciScore for 10.1101/2020.09.17.301861: (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
Antibodies Sentences Resources Following secondary labeling with fluorescent anti-His6 and anti-IgY antibodies yeast were washed once with PBS/0.2% BSA and resuspended in ice cold PBS for flow cytometric analysis. anti-His6suggested: Noneanti-IgYsuggested: NoneSoftware and Algorithms Sentences Resources The resulting SAM files were filtered to remove sites with a Phred quality score (Q score) of less than 30 and translated to amino acid sequences. Phredsuggested: (Phred, RRID:SCR_001017)Exome data from gnomAD v2.1.1 and genome data from gnomAD v3 were combined to generate a data set representing over 250,000 individuals. gnomADsuggested: …SciScore for 10.1101/2020.09.17.301861: (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
Antibodies Sentences Resources Following secondary labeling with fluorescent anti-His6 and anti-IgY antibodies yeast were washed once with PBS/0.2% BSA and resuspended in ice cold PBS for flow cytometric analysis. anti-His6suggested: Noneanti-IgYsuggested: NoneSoftware and Algorithms Sentences Resources The resulting SAM files were filtered to remove sites with a Phred quality score (Q score) of less than 30 and translated to amino acid sequences. Phredsuggested: (Phred, RRID:SCR_001017)Exome data from gnomAD v2.1.1 and genome data from gnomAD v3 were combined to generate a data set representing over 250,000 individuals. gnomADsuggested: (Genome Aggregation Database, RRID:SCR_014964)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: We did not find any issues relating to colormaps.
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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SciScore for 10.1101/2020.09.17.301861: (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
Antibodies Sentences Resources Following secondary labeling with fluorescent anti-His6 and anti-IgY antibodies yeast were washed once with PBS/0.2% BSA and resuspended in ice cold PBS for flow cytometric analysis. anti-His6suggested: Noneanti-IgYsuggested: NoneSoftware and Algorithms Sente… SciScore for 10.1101/2020.09.17.301861: (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
Antibodies Sentences Resources Following secondary labeling with fluorescent anti-His6 and anti-IgY antibodies yeast were washed once with PBS/0.2% BSA and resuspended in ice cold PBS for flow cytometric analysis. anti-His6suggested: Noneanti-IgYsuggested: NoneSoftware and Algorithms Sentences Resources The resulting SAM files were filtered to remove sites with a Phred quality score (Q score) of less than 30 and translated to amino acid sequences. Phredsuggested: (Phred, RRID:SCR_001017)Exome data from gnomAD v2.1.1 and genome data from gnomAD v3 were combined to generate a data set representing over 250,000 individuals. gnomADsuggested: (Genome Aggregation Database, RRID:SCR_014964)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: We did not find any issues relating to colormaps.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
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