Furin-cleavage site is present in an antiparallel β-strand in SARS-CoV2 Spike protein

  1. Arif Bashir
  2. Naveed Nazir Shah

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Furin cleavage-site (CS) present between the S1/S2 junction in SARS-CoV2 spike (S) protein is critical to drive the fusion of SARS-CoV2 with the host cell. SARS-CoV2 falls in the sarbecovirus lineage that doesn’t comprise of furin CS and therefore makes its origin enigmatic. The available wild-type (Wt) SARS-CoV2 S protein with PDB ID: 6yvb lacks a stretch of amino acid including furin CS as well. All investigators till date have shown this stretch existing in the form of a loop. We are for the first time reporting that this stretch comprises of 14 amino acid residues (677QTNSPRRARSVASQ689), forming an antiparallel β-sheet comprising of PRRAR furin CS. We observed the presence of this antiparallel β-sheet in MERS spike protein as well. While switching over from Wt. SARS-CoV2 with PRRAR furin CS to B.1.1.7 variant with HRRAR furin CS, we found 3% increase in the percentage content of β stands. Interestingly, we found that the change of B.1.1.7 to B.1.617 variant comprising of RRRAR furin CS shifted the percentage secondary structure back to that found in Wt. SARS-CoV2. We anticipate that this β-sheet is used as a docking site by host cell proteases to act on furin-CS. Additionally, we studied the interaction of modeled SARS-CoV2 S protein with transmembrane protease, serine 2 (TMPRSS2), and furin proteases, which clearly highlighted that these proteases exclusively uses furin CS located in β-sheet to cleave the SARS-CoV2 S protein at its S1/S2 junction.

Article activity feed

  1. Version published to 10.1101/2022.02.18.481028v3 on bioRxiv
  2. Version published to 10.1101/2022.02.18.481028v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.02.18.481028: (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

    Software and Algorithms
    SentencesResources
    Various SARS-CoV2 mutants such as SARS-CoV2 (K417N), SARS-CoV2 (E484K), SARS-CoV2 (N501Y), SARS-CoV2 (E484Q), SARS-CoV2 (L452R), SARS-CoV2 double-mutant (E484Q and L452R), SARS-CoV2 triple-mutant (K417N, E484K, and N501Y) were introduced in silico through PyMol software.
    PyMol
    suggested: (PyMOL, RRID:SCR_000305)
    Electrostatic potential of wild-type SARS-CoV2 and its mutants were generated through PyMol software Protein◻Protein
    Protein◻Protein
    suggested: None

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04348396RecruitingClinical and Biological Predictors of COVID-19 Disease in Ol…
    NCT04366089RecruitingOxygen-Ozone as Adjuvant Treatment in Early Control of COVID…

    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 15. 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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    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.

  4. Version published to 10.1101/2022.02.18.481028v1 on bioRxiv