Analyzing the interaction of human ACE2 and RBD of spike protein of SARS-CoV-2 in perspective of Omicron variant

  1. Arijit Samanta
  2. Syed Sahajada Mahafujul Alam
  3. Safdar Ali
  4. Mehboob Hoque

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Abstract

The newly identified Omicron (B.1.1.529) variant of Severe Acute Respiratory Syndrome Voronavirus 2 (SARS-CoV-2) has steered concerns across the world due to the possession of large number of mutations leading to high infectivity and vaccine escape potential. The Omicron variant houses 32 mutations in S protein alone. The viral infectivity is determined mainly by the ability of spike (S) protein receptor binding domain (RBD) to bind to the human Angiotensin I Converting Enzyme 2 (hACE2) receptor. In this paper, the interaction of the RBDs of SARS-CoV-2 variants with hACE2 was analyzed by using protein-protein docking and compared with the novel Omicron variant. Our findings reveal that the Omicron RBD interacts strongly with hACE2 receptor via unique amino acid residues as compared to the Wuhan and many other variants. However, the interacting residues of RBD are found to be the same in Lamda (C.37) variant. These unique binding of Omicron RBD with hACE2 suggests an increased potential of infectivity and vaccine evasion potential of the new variant. The evolutionary drive of the SARS-CoV-2 may not be exclusively driven by RBD variants but surely provides for the platform for emergence of new variants.

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    SciScore for 10.1101/2021.12.23.473991: (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
    For the prediction of coding sequence of RDB of S protein from all variants, Multiple Sequence Alignment (MSA) were performed by using MAFFT webtool (version 7) (Katoh and Standley, 2013).
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    Protein Structure Analysis (ProSA)-web server (https://prosa.services.came.sbg.ac.at/prosa.php) uses Z-score (indicates the overall model quality) to evaluate the models. 2.5. Protein-protein Docking: Docking between hACE2 and RBD of S protein of different variants of SARS-CoV-2 was performed using ClusPro server (https://cluspro.org) (Kozakov et al., 2017).
    ClusPro server
    suggested: (ClusPro, RRID:SCR_018248)
    Crystal PDB structure of hACE2 was uploaded in the ClusPro server as a receptor and validated PDB structure of RBD of S protein of all variants were uploaded one by one as a ligand.
    ClusPro
    suggested: (ClusPro, RRID:SCR_018248)
    The selected cluster models were downloaded in PDB format for further analysis. 2.6. Analysis of Direct Contact Residues of hACE2 : S Protein RBD: Direct contact residues between hACE2 : RBD of S protein of 25 all variants were analysed using PDBSum (https://www.ebi.ac.uk/thorntonsrv/databases/pdbsum/Generate.html) (Laskowski, 2001).
    PDBSum
    suggested: (PDBsum, RRID:SCR_006511)
    ClustalW multiple sequence alignment was used for multiple comparisons, neighbour-joining phylogenies were estimated, and 1000 bootstraps were used (Liu et al., 2020; Laskar and Ali, 2021a).
    ClustalW
    suggested: (ClustalW, RRID:SCR_017277)

    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.

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

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  2. Version published to 10.1101/2021.12.23.473991v1 on bioRxiv