CIGB-300 synthetic peptide, an antagonist of CK2 kinase activity, as a treatment for Covid-19. A computational biology approach

  1. Jamilet Miranda
  2. Ricardo Bringas
  3. Jorge Fernández-de-Cossio
  4. Yasser Perera

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Abstract

Drug repositioning became the first choice for treating Covid-19 patients due to the urgent need to deal with the pandemic. Similarities in the hijacking mechanisms used by SARS-CoV-2 and several type of cancer, suggest the repurposing of cancer drugs to treat Covid-19. CK2 kinase antagonists have been proposed for the treatment of cancer. A recent study in cells infected with SARS-CoV-2 virus found a significant CK2 kinase activity, and the use of a CK2 inhibitor showed antiviral responses. CIGB-300, originally designed as an anticancer peptide, is an antagonist of CK2 kinase activity that binds to CK2 phospho-acceptor sites. Recent preliminary results show an antiviral activity of CIGB-300 versus a surrogate model of coronavirus. Here we present a computational biology study that provides evidences at the molecular level of how CIGB-300 might interfere with SARS-CoV-2 life cycle inside infected human cells. First, from SARS-CoV studies, we infer the potential incidence of CIGB-300 in SARS-CoV-2 interference on immune response. Next, from the analysis of multiple Omics data, we propose the action of CIGB-300 since early stage of viral infections perturbing the virus hijacking of RNA splicing machinery. It was also predicted the interference of CIGB-300 in virus-host interactions responsible for the high infectivity and the particular immune response to SARS-CoV-2 infection. Further, we provide evidences of CIGB-300 attenuation of phenotypes related to muscle, bleeding, coagulation and respiratory disorders.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.26.453805: (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
    Public Data: Protein sequence information was downloaded from UniprotKB database [73] https://www.uniprot.org/.
    UniprotKB
    suggested: (UniProtKB, RRID:SCR_004426)
    A total of 332 humand-SARS-CoV-2 protein-protein interactions from Gordon et al. [5] were downloaded from Biogrid database [74] at https://thebiogrid.org/225737/publication/comparative-host-coronavirus-protein-interaction-networks-reveal-pan-viral-disease-mechanisms.html#!.
    Biogrid
    suggested: (BioGrid Australia, RRID:SCR_006334)
    Information of CK2 Substrates was downloaded from PhosphoSitePlus at (https://www.phosphosite.org/) [75].
    https://www.phosphosite.org/
    suggested: (PhosphoSitePlus: Protein Modification Site, RRID:SCR_001837)
    For Gene Set Enrichment Analysis we used GSEA version 4.1.0 for windows [79, 80].
    GSEA
    suggested: (SeqGSEA, RRID:SCR_005724)
    Functional analysis of enriched pathways and reactions was performed using Reactome Pathway Knowledgebase [84] at: https://reactome.org/.
    Reactome Pathway Knowledgebase
    suggested: None
    GeneCodis 4.0, at https://genecodis.genyo.es/, was used for diseases enrichment analysis [85].
    GeneCodis
    suggested: (GeneCodis, RRID:SCR_006943)
    BiNGO plugin [86], available from Cytoscape Application Manager, was used to determine and visualize Gene Ontology (GO) categories statistically overrepresented.
    BiNGO
    suggested: None
    Cytoscape
    suggested: (Cytoscape, RRID:SCR_003032)
    Additional statistical analysis and graphs were generated and plotted using GraphPad Prism version 5.00 software (GraphPad Software, San Diego, CA, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

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

    IdentifierStatusTitle
    NCT04663737RecruitingEvaluating Safety, Pharmacokinetics and Clinical Benefit of …

    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.

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

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  2. Version published to 10.1101/2021.07.26.453805v1 on bioRxiv