Coronavirus-associated molecular mimicry through homology to a SARS-CoV-2 peptide could be leading to susceptibility in patients with HLA-A*02:01 and HLA-A*24:02 serotypes

  1. Yekbun Adiguzel

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Abstract

This study aims to predict autoimmunity-related pathological mechanisms that possess risk for individuals with specific human leukocyte antigen (HLA) serotypes and shared by certain coronaviruses including SARS-CoV-2, based on homology to a SARS-CoV-2 peptide. With the given aim, 1-) coronavirus-associated sequences, which are homologous to the 15mer SARS-CoV-2 peptide CFLGYFCTCYFGLFC, are obtained. 2-) Human peptides that have at least 7 residue matches with those coronavirus sequences, and the SARS-CoV-2 15mer, are found. 3-) Epitope pairs, which are sourced by those aligned coronavirus and human sequences are identified. 4-) Epitope pairs that are predicted to bind strongly not only to the same HLA allele with each other but also to the same HLA allele as those of the respective alignment of the SARS-CoV-2 peptide are selected. Following are the identified proteins or peptides (with HLA-A*02:01 or HLA-A*24:02 epitopes), as described in 1-to-4: Immunoglobulin heavy chain junction regions, CRB1 isoform I precursor, slit homolog 2 protein, hCG1995581, hCG2028737, phospholipid phosphatase-related protein type 2. Among those, CRB1 isoform I precursor sequence with the predicted HLA-A*24:02 epitope aligns with the highest number of different sequences. Results imply autoimmunity risk in COVID-19 patients with HLA-A*02:01 and HLA-A*24:02 serotypes, through molecular mimicry, as a shared pathogenicity risk that can be prevalent upon getting infected with certain coronaviruses. These can pave way to improved risk groups’ assessment and autoimmunity treatment options, for COVID-19 and its associated diseases. Also, the approach in this study can be used to predict prospective pathologies of the transmissible variants in susceptible humans.

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  1. Version published to 10.1101/2021.01.28.428642v3 on bioRxiv
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    SciScore for 10.1101/2021.01.28.428642: (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
    The CFLGYFCTCYFGLFC sequence was obtained by performing blastx [33] at NCBI [34], between the reference genome of query input SARS-CoV-2 (NC_045512.2) and P. vivax (taxid:5855) [30].
    blastx
    suggested: (BLASTX, RRID:SCR_001653)
    NCBI
    suggested: (NCBI, RRID:SCR_006472)
    It was the aligned query sequence in the tblastx output that revealed the top identity between the query and subject, which was afterwards utilized as input for NCBI blastp search, by limiting the search to SARS-CoV-2 (taxid:2697049), to ensure that the sequence is expressed [30].
    blastp
    suggested: (BLASTP, RRID:SCR_001010)
    36,37], NetMHCpan 4.1 [38], and PickPocket 1.1 [39]
    PickPocket
    suggested: None
    Summary information about the identified proteins (or peptides in case of immunoglobulin heavy chain junction regions) is collected by searching the sequence ID of the aligned subject sequence in the blastp results at Entrez (NCBI), and then searching the encoding gene ID, which is indicated at the UniProt (www.uniprot.org) [42], to retrieve the UniProtKB number.
    UniProtKB
    suggested: (UniProtKB, RRID:SCR_004426)

    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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  3. Version published to 10.1101/2021.01.28.428642v2 on bioRxiv
  4. Version published to 10.1101/2021.01.28.428642v1 on bioRxiv