Pharmacophore-based peptide biologics neutralize SARS-CoV-2 S1 and deter S1-ACE2 interaction in vitro

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   ScreenIT

   Dec 31, 2020

   SciScore for 10.1101/2020.12.30.424801: (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
   After the cells were washed three times with PBS, incubated with serum free media with primary antibody anti-ACE2 (1:100	anti-ACE2 suggested: (Enzo Life Sciences Cat# ALX-804-722-C100, RRID:AB_11180102)
   Experimental Models: Cell Lines
   Sentences	Resources
   For CSNPs-binding, hACE2-overexpressed Hek293 cells were incubated with 10 uM peptide for 1 hour and then treated and incubated with 5 uM SARS-CoV-1 S1 protein-His Tag (AcroBiosystems, S1N-C52H3-100UG, USA) for 24 hours.	Hek293 suggested: None
   Software and Algorithms
   Sentences	Resources
   As g_mmpbsa tool is compatible with older versions of GROMACS (versions 5 or …

   SciScore for 10.1101/2020.12.30.424801: (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
   After the cells were washed three times with PBS, incubated with serum free media with primary antibody anti-ACE2 (1:100	anti-ACE2 suggested: (Enzo Life Sciences Cat# ALX-804-722-C100, RRID:AB_11180102)
   Experimental Models: Cell Lines
   Sentences	Resources
   For CSNPs-binding, hACE2-overexpressed Hek293 cells were incubated with 10 uM peptide for 1 hour and then treated and incubated with 5 uM SARS-CoV-1 S1 protein-His Tag (AcroBiosystems, S1N-C52H3-100UG, USA) for 24 hours.	Hek293 suggested: None
   Software and Algorithms
   Sentences	Resources
   As g_mmpbsa tool is compatible with older versions of GROMACS (versions 5 or lower), the “tpr” files created by GROMACS 2019.6 were recreated through GROMACS 5.1 and used for binding energy calculation.	GROMACS suggested: (GROMACS, RRID:SCR_014565)
   Computational tools used in this study: For simple visualization and collecting structural insights of the SARS-CoV-2 spike and ACE2 proteins, free available packages of VMD (61), Pymol (https://pymol.org), and Chimera (62) were utilized.	Pymol suggested: (PyMOL, RRID:SCR_000305)
   For CSNPs-binding, hACE2-overexpressed Hek293 cells were incubated with 10 uM peptide for 1 hour and then treated and incubated with 5 uM SARS-CoV-1 S1 protein-His Tag (AcroBiosystems, S1N-C52H3-100UG, USA) for 24 hours.	AcroBiosystems suggested: (ACRObiosystems, RRID:SCR_012550)

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   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).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   To overcome this limitation, two research groups have stabilized the α1 helix by increasing the helical bundles and designed peptide biologics that could effectively inhibit SARS-CoV-2 cell entry (44, 45). However, this modification increases the size of these peptides by ~3-4 folds, increasing the cost of synthesis and formulation. We and others have previously used peptide stapling to enhance the target specificity of therapeutic peptides (28, 51). In fact, Fiarlie and his co-workers found that the helical-constrained compounds hold comparatively similar biological potencies in PPI as their parent proteins. They constructed four such compounds and proposed that downsized-constrained peptides could be of great value in biological PPIs and medicine (52). Unfortunately, we could not synthesize the CSNP1 to compare its potency with CSNP2; however, CSNP3 (a relatively shorter version of CSNP1) was unable to bind SARS-CoV-2 S1 (Figure 5). This notion suggests that in addition to the structural integrity, optimum length and the featured pharmacophores are vital for CSNP to bind RBD. Together, we suggest that structure guided computational medicinal chemistry and click chemistry approaches might be useful in designing CSNPs to enhance tethering to their targets. Collectively, we suggest that CSNP2 and CSNP4 are stable peptide that deter the binding of ACE2 and S1 subunit of SARS-CoV-2 and could be potent antidote for COVID-19.

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 28. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

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   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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   Version published to 10.1101/2020.12.30.424801v1 on bioRxiv

   Dec 30, 2020