The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling

  1. Abdulrasheed Palakkott
  2. Aysha Alneyadi
  3. Khalid Muhammad
  4. Ali H. Eid
  5. Khaled Amiri
  6. Mohammed Akli Ayoub
  7. Rabah Iratni

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Abstract

Objectives

The coronavirus disease-19 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the molecular and cellular levels, the SARS-Cov-2 uses its envelope glycoprotein, the spike S protein, to infect the target cells in the lungs via binding with their transmembrane receptor, the angiotensin-converting enzyme 2 (ACE2). Here, we wanted to invesitgate if other molecular targets and pathways may be used by SARS-Cov-2.

Methods

We investigated the possibility for the spike 1 S protein and its receptor-binding domain (RBD) to target the epidermal growth factor receptor (EGFR) and its downstream signaling pathway in vitro using the lung cancer cell line (A549 cells). Protein expression and phosphorylation was examined upon cell treatment with the recombinant full spike 1 S protein or RBD.

Results

We demonstrate for the first time the activation of EGFR by the Spike 1 protein associated with the phosphorylation of the canonical ERK1/2 and AKT kinases and an increase of survivin expression controlling the survival pathway.

Conclusions

Our study suggests the putative implication of EGFR and its related signaling pathways in SARS-CoV-2 infectivity and Covid-19 pathology. This may open new perspectives in the treatment of Covid-19 patients by targeting EGFR.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.10.491351: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cell culture, chemicals and antibodies: The lung cancer cells (A549) used in this study were obtained from Cell Line Service (CLS)-GmbH and were maintained in RPMI (Cat. # 00506 Gibco, Life Technologies, Rockville, UK) complemented with 10% fetal bovine serum (FBS) (Cat. # 02187 Gibco, Life Technologies, Rockville, UK) and 100 U/ml penicillin streptomycin glutamine (Cat. # 01574 Gibco, Life Technologies, Rockville,
    A549
    suggested: None
    Antibodies against phospho-EGFR (Cat. # 4407), EGFR (Cat. # 4267), phospho-ERK1/2 (Cat. # 9106), ERK1/2 (Cat. # 4695),
    phospho-EGFR
    suggested: None
    EGFR
    suggested: (Nolan lab - Stanford Cat# 4267, RRID:AB_2864406)
    phospho-ERK1/2
    suggested: None
    ERK1/2
    suggested: (Cell Signaling Technology Cat# 4695, RRID:AB_390779)
    Horseradish peroxidase-conjugated anti-IgG was used as secondary antibody.
    anti-IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell culture, chemicals and antibodies: The lung cancer cells (A549) used in this study were obtained from Cell Line Service (CLS)-GmbH and were maintained in RPMI (Cat. # 00506 Gibco, Life Technologies, Rockville, UK) complemented with 10% fetal bovine serum (FBS) (Cat. # 02187 Gibco, Life Technologies, Rockville, UK) and 100 U/ml penicillin streptomycin glutamine (Cat. # 01574 Gibco, Life Technologies, Rockville,
    A549
    suggested: None

    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.
    • 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.

    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.

  2. Version published to 10.1101/2022.05.10.491351v1 on bioRxiv