Antiviral cyclic peptides targeting the main protease of SARS-CoV-2
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Abstract
RaPID mRNA display was used for the discovery of antiviral cyclic peptides that potently and selectively inhibit SARS-CoV-2 M pro . The most potent inhibitor exhibited a novel binding mode, interacting with residues across the homodimer interface.
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SciScore for 10.1101/2021.08.23.457419: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Contamination: Cells were sub-cultured between 70-90% confluency and tested regularly to ensure free of mycoplasma contamination. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cytotoxicity and targeted proteomics on HEK293-ACE2-TMPRSS2 cell line: HEK293-ACE2-TMPRSS2 cells were maintained in Dulbecco’s Modified Eagle Medium (DMEM) with 4.5 g/L D-Glucose, L-Glutamine and 110 mg/L sodium pyruvate (Gibco), supplemented with 10% foetal calf serum (Hyclone). HEK293-ACE2-TMPRSS2suggested: NoneRecombinant DNA Sentences Resources Plasmi… SciScore for 10.1101/2021.08.23.457419: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Contamination: Cells were sub-cultured between 70-90% confluency and tested regularly to ensure free of mycoplasma contamination. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cytotoxicity and targeted proteomics on HEK293-ACE2-TMPRSS2 cell line: HEK293-ACE2-TMPRSS2 cells were maintained in Dulbecco’s Modified Eagle Medium (DMEM) with 4.5 g/L D-Glucose, L-Glutamine and 110 mg/L sodium pyruvate (Gibco), supplemented with 10% foetal calf serum (Hyclone). HEK293-ACE2-TMPRSS2suggested: NoneRecombinant DNA Sentences Resources Plasmid construction: The gene of the SARS-CoV-2 main protease (Mpro)27 was cloned in between the NdeI and XhoI sites of the T7 vector pET-47b (+). pET-47bsuggested: NoneSoftware and Algorithms Sentences Resources Data sets were analyzed with Prism 9.2 (Graph Pad Software, USA) to generate dose-response curves and calculate IC50 values, as well as to generate Michaelis-Menten curves and calculate Ki values assuming the appropriate inhibition mode. Prismsuggested: (PRISM, RRID:SCR_005375)The structure was refined by iterative rounds of rebuilding in Coot 63, and twin refinement in Refmac64,65. Cootsuggested: (Coot, RRID:SCR_014222)Inhibition curves and 50% (EC50) effective concentrations were determined by non-linear regression analysis using GraphPad Prism software (version 9.1.2, GraphPad software, USA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)69 Extracted ion chromatograms for fragment ions derived from tryptic peptides were plotted using Xcalibur Qual Browser (Thermo Scientific). Xcalibur Qual Browsersuggested: NoneResults 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: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04535167 Completed First-In-Human Study To Evaluate Safety, Tolerability, And P… NCT04960202 Recruiting A Study of PF-07321332/Ritonavir in Nonhospitalized High Ris… 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 19. 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.
Results from scite Reference Check: We found no unreliable references.
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