The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2
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Abstract
The rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S binds ACE2 on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.
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SciScore for 10.1101/2020.03.16.994236: (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 Cells were washed twice, incubated with secondary antibody (1/100 dilution of chicken anti-HIS-FITC polyclonal from Immunology Consultants Laboratory; or 1/250 anti-human IgG-APC clone HP6017 from BioLegend) for 30 minutes on ice, washed twice again, and fluorescence of the total population after gating by FSC-SSC to exclude debris was measured on a BD Accuri C6. anti-HIS-FITCsuggested: (Miltenyi Biotec Cat# 130-098-808, RRID:AB_2751026)anti-human IgG-APCsuggested: NoneSoftware and Algorithms S… SciScore for 10.1101/2020.03.16.994236: (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 Cells were washed twice, incubated with secondary antibody (1/100 dilution of chicken anti-HIS-FITC polyclonal from Immunology Consultants Laboratory; or 1/250 anti-human IgG-APC clone HP6017 from BioLegend) for 30 minutes on ice, washed twice again, and fluorescence of the total population after gating by FSC-SSC to exclude debris was measured on a BD Accuri C6. anti-HIS-FITCsuggested: (Miltenyi Biotec Cat# 130-098-808, RRID:AB_2751026)anti-human IgG-APCsuggested: NoneSoftware and Algorithms Sentences Resources Raw and processed deep sequencing data are deposited in NCBI’s Gene Expression Omnibus (GEO) with series accession no. GSE147194. Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)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.
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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