Global conserved RBD fraction of SARS-CoV-2 S-protein with T500S mutation in silico significantly blocks ACE2 and rejects viral spike

  1. Amrita Banerjee
  2. Mehak Kanwar
  3. Dipannita Santra
  4. Smarajit Maiti

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Abstract

Background

SARS-CoV-2 developed global-pandemic with millions of infections/deaths. As it is urgently necessary it is assumed that some blockers/inhibitors of ACE2 could be helpful to resist the binding of viral-spike Receptor-Binding-Domain (RBD).

Methods

Here, conserved RBD from 186-countries were compared with WUHAN-Hu-1 wild-type (CLUSTAL-X2/Pymol). The RBD of ACE2-bound nCOV2 crystal-structure 6VW1 was analyzed by Haddock-PatchDock. Extensive structural study/trial to introduce point/double/triple mutations in the different locations of CUT4 (most-effective from total 4 proposed fragments; CUTs) were tested with Swiss-Model-Expacy.

Results

Blind-docking of mutated-CUTs in ACE2 completely rejected the nCOV2 binding to ACE2. Further, competitive-docking/binding-analyses (by PRODIGY) demonstrated few more bonding (LYS31-PHE490 and GLN42-GLN498) of CUT4 (than wild) and hindered TYR41-THR500 interaction with ACE2. Moreover, mutated-CUT4 even showed higher blocking effect against spike-ACE2 binding.

Conclusion

In summary, CUT4-mutant rejects whole glycosylated-nCoV2 in all pre-dock, post-dock and competitive-docking conditions. The present work strategy is relevant because it could be able to block at the first level entry of the virus to the host cells.

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  1. Version published to 10.1186/s41231-022-00109-5
  2. ScreenIT

    SciScore for 10.1101/2021.04.25.441361: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingAfter mutation induction, blind docking studies of different mutated CUTs with ACE2 were performed using Haddock 2.4 [12], and Hawkdock [13,14].
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The results were analyzed using Pymol [10].
    Pymol
    suggested: (PyMOL, RRID:SCR_000305)
    (https://www.ncbi.nlm.nih.gov/).
    https://www.ncbi.nlm.nih.gov/
    suggested: (GENSAT at NCBI - Gene Expression Nervous System Atlas, RRID:SCR_003923)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 18 and 14. 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:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.04.25.441361 on bioRxiv