Structural insight into the putative role of novel SARS CoV-2 E protein in viral infection: a potential target for LAV development and therapeutic strategies

  1. Manish Sarkar
  2. Soham Saha

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Abstract

The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases. Using the bioinformatics and structural modeling approach, we modeled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS-CoV-1, and is highly conserved in the N-terminal regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modeling, we found that the most favorable structure could function as a gated proton channel. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds. Additionally, two distinct “core” structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral proton channeling activity which may play a critical role in viral infection. In addition, it provides a structural basis and additional avenues for LAV development and generating therapeutic interventions against the virus.

Significance Statement

Structural modeling of the novel SARS-CoV-2 envelope protein (E-protein) demonstrating its possible proton channeling activity

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  1. ScreenIT

    SciScore for 10.1101/2020.05.11.088781: (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
    Multiple sequence alignment: In order to assess the conservation among candidate coronavirus E-proteins, we performed a protein-protein BLAST (
    BLAST
    suggested: (BLASTX, RRID:SCR_001653)
    Using a 90-100% sequence identity as filters, we aligned the resulting sequences using the online alignment tool Clustal Omega (27) and MegaX (28).
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    Jalview (www.jalview.org) was used for visualizing the sequence alignment, conservation score, quality of alignment and consensus residue for each position.
    Jalview
    suggested: (Jalview, RRID:SCR_006459)
    The structures obtained from these modeling servers were validated by scores obtained from the MolProbity (32, 33).
    MolProbity
    suggested: (MolProbity, RRID:SCR_014226)
    Structure visualizations: The structural visualizations of the different models were performed using PYMOL.
    PYMOL
    suggested: (PyMOL, RRID:SCR_000305)
    The lining residues are annotated from the UniProt database and mapped along with the cavity.
    UniProt
    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 12 and 13. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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 10.1101/2020.05.11.088781 on bioRxiv