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. 2022 Jan 1;27(1):260.
doi: 10.3390/molecules27010260.

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

Affiliations

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

Trina Ekawati Tallei et al. Molecules. .

Abstract

Before entering the cell, the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. Hence, this RBD is a critical target for the development of antiviral agents. Recent studies have discovered that SARS-CoV-2 variants with mutations in the RBD have spread globally. The purpose of this in silico study was to determine the potential of a fruit bromelain-derived peptide. DYGAVNEVK. to inhibit the entry of various SARS-CoV-2 variants into human cells by targeting the hACE binding site within the RBD. Molecular docking analysis revealed that DYGAVNEVK interacts with several critical RBD binding residues responsible for the adhesion of the RBD to hACE2. Moreover, 100 ns MD simulations revealed stable interactions between DYGAVNEVK and RBD variants derived from the trajectory of root-mean-square deviation (RMSD), radius of gyration (Rg), and root-mean-square fluctuation (RMSF) analysis, as well as free binding energy calculations. Overall, our computational results indicate that DYGAVNEVK warrants further investigation as a candidate for preventing SARS-CoV-2 due to its interaction with the RBD of SARS-CoV-2 variants.

Keywords: COVID-19; RBD mutation; SARS-CoV-2 variants; bromelain; in silico; molecular dynamics simulation; peptide; peptide-protein interaction; receptor-binding domain.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The genomic structure of the S glycoprotein of SARS-CoV-2 showing the position of each gene and the impactful mutations in the RBD.
Figure 2
Figure 2
The 3D (A) and 2D (B) structures of bromelain-derived peptide ASP-TYR-GLY-ALA-VAL-ASN-GLU-VAL-LYS (DYGAVNEVK).
Figure 3
Figure 3
Sketch diagram depicting the 3D (A) and 2D (B) interactions between bromelain-derived peptide and RBD WT from LigPlot+.
Figure 4
Figure 4
Sketch diagram depicting the 3D (A) and 2D (B) interaction between bromelain-derived peptide and RBD BR by LigPlot+. RBD BR contains the mutations K417T, E484, and N501Y.
Figure 5
Figure 5
Schematic representation demonstrating bromelain peptide (green) inhibiting RBD (yellow) adhesion to hACE2 (light blue).
Figure 6
Figure 6
The root-mean-square deviation (RMSD) and radius of gyration (Rg) values obtained during molecular dynamics simulations of bromelain peptide with the RBD wild type (WT) and BR, US, UK, and NG variants.
Figure 6
Figure 6
The root-mean-square deviation (RMSD) and radius of gyration (Rg) values obtained during molecular dynamics simulations of bromelain peptide with the RBD wild type (WT) and BR, US, UK, and NG variants.
Figure 7
Figure 7
The root-mean-square fluctuation (RMSF) analysis showing the interaction and conformational changes between bromelain peptide and the spike protein RBD unit wild type apo and holo forms (left) as well as RBD variants and peptide complexes (right).

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References

    1. Planas D., Bruel T., Grzelak L., Guivel-Benhassine F., Staropoli I., Porrot F., Planchais C., Buchrieser J., Rajah M.M., Bishop E., et al. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat. Med. 2021;27:917–924. doi: 10.1038/s41591-021-01318-5. - DOI - PubMed
    1. Padilla-Sanchez V. SARS-CoV-2 Structural Analysis of Receptor Binding Domain New Variants from United Kingdom and South Africa. Res. Ideas Outcomes. 2021;7:e62936. doi: 10.3897/rio.7.e62936. - DOI
    1. Albini A., Di Guardo G., Noonan D.M.C., Lombardo M. The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: Implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies. Intern. Emerg. Med. 2020;15:759–766. doi: 10.1007/s11739-020-02364-6. - DOI - PMC - PubMed
    1. Lukassen S., Chua R.L., Trefzer T., Kahn N.C., Schneider M.A., Muley T., Winter H., Meister M., Veith C., Boots A.W., et al. SARS -CoV-2 receptor ACE 2 and TMPRSS 2 are primarily expressed in bronchial transient secretory cells. EMBO J. 2020;39:e105114. doi: 10.15252/embj.2020105114. - DOI - PMC - PubMed
    1. Mahase E. Covid-19: Where are we on vaccines and variants? BMJ. 2021;372:n597. doi: 10.1136/bmj.n597. - DOI - PubMed

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