Impacts of 203/204: RG>KR mutation in the N protein of SARS-CoV-2

  1. Majid Vahed
  2. Tess M Calcagno
  3. Elena Quinonez
  4. Mehdi Mirsaeidi

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Abstract

We present a structure-based model of phosphorylation-dependent binding and sequestration of SARS-CoV-2 nucleocapsid protein and the impact of two consecutive amino acid changes R203K and G204R. Additionally, we studied how mutant strains affect HLA-specific antigen presentation and correlated these findings with HLA allelic population frequencies. We discovered RG>KR mutated SARS-CoV-2 expands the ability for differential expression of the N protein epitope on Major Histocompatibility Complexes (MHC) of varying Human Leukocyte Antigen (HLA) origin. The N protein LKR region K203, R204 of wild type (SARS-CoVs) and (SARS-CoV-2) observed HLA-A*30:01 and HLA-A*30:21, but mutant SARS-CoV-2 observed HLA-A*31:01 and HLA-A*68:01. Expression of HLA-A genotypes associated with the mutant strain occurred more frequently in all populations studied.

Importance

The novel coronavirus known as SARS-CoV-2 causes a disease renowned as 2019-nCoV (or COVID-19). HLA allele frequencies worldwide could positively correlate with the severity of coronavirus cases and a high number of deaths.

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  1. ScreenIT

    SciScore for 10.1101/2021.01.14.426726: (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
    Data retrieval and sequence alignment: We used BLASTP programs from the NCBI database search (23) to find the LKR N-protein sequence (43 nucleotides long) of all SARS-CoV-2.
    BLASTP
    suggested: (BLASTP, RRID:SCR_001010)
    NCBI
    suggested: (NCBI, RRID:SCR_006472)
    Conserved and varied residues were identified by using the WebLogo program (
    WebLogo
    suggested: (WEBLOGO, RRID:SCR_010236)
    Clustal Omega is used to apply mBed algorithms for guide trees.
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    ClustalW alignment tools executed to output alignment format (27).
    ClustalW
    suggested: (ClustalW, RRID:SCR_017277)
    The tertiary structure of the full 419 a.a. sequencing of N-proteins was predicted using the IntFOLD5 server (PYMOL)
    PYMOL
    suggested: (PyMOL, RRID:SCR_000305)
    All of the structures were visualized using PYMOL Chimera software Version 1.7.4 (
    PYMOL Chimera
    suggested: (Cube-DB, RRID:SCR_013233)

    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: 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.

    About SciScore

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  2. Version published to 10.1101/2021.01.14.426726 on bioRxiv