Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps

  1. Aitor Blanco-Míguez
  2. Borja Sánchez

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Abstract

COVID-2019 has progressed in around 10-15% of patients to an acute respiratory distress syndrome characterized by extensive pulmonary inflammation and elevated production of pro-inflammatory cytokines. Neutrophil activation seems to be crucial in the initiation and perpetuation of this exacerbated lung inflammation. However, the precise mechanisms by which this activation occurs remain yet elusive. To this end, this in silico study tried to identify potential proinflammatory inducing peptides (PIPs) produced by the action of the elastase released in neutrophil-extracellular traps over SARS-CoV-2 particles. We found nine potential PIPs exclusive from the SARS-CoV-2, showing homology against T cell recognition epitopes. Moreover, 78 percent of these exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, suggesting that high PIP concentrations might be released following SARS-CoV-2 huge replication rate. Therefore, these PIPs might play a role in the exacerbated inflammatory response observed in some patients.

Highlights

  • Nine potential PIPs were predicted exclusive from the SARS-CoV-2.

  • SARS-CoV-2 PIPs showed homology against T cell recognition epitopes.

  • Most of PIPs were produced by enzymatic cleavage of the spike glycoproteins.

  • The release of these PIPs might be related to the increased inflammatory response observed in the patients.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.02.072439: (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

    Experimental Models: Cell Lines
    SentencesResources
    SARS exclusive belonging prediction: Exclusive belonging of the predicted PIPs to the SARS subtype was assessed aligning them against other the known human coronaviruses, i.e. MERS-CoV, HCoV-229E, HCoV-NL63, HCoV-HKU1 and HCoV-OC43 (NCBI Reference Sequences: NC_004718.3, NC_019843.3, NC_002645.1, NC_005831.2, NC_006577.2, NC_006213.1, respectively), using BLASTp version 2.2.31.
    HCoV-NL63
    suggested: RRID:CVCL_RW88)
    Software and Algorithms
    SentencesResources
    B and T cell response capability prediction: In order to check the capability of the predicted PIPs, they were aligned against the potential B and T cell epitopes reported by Grifoni et al (Grifoni et al., 2020) using BLASTp version 2.2.31 (Altschul et al., 1990).
    BLASTp
    suggested: (BLASTP, RRID:SCR_001010)

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

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  2. Version published to 10.1101/2020.05.02.072439v1 on bioRxiv