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Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactions.
- Source :
-
Frontiers in molecular biosciences [Front Mol Biosci] 2023 Nov 29; Vol. 10, pp. 1270511. Date of Electronic Publication: 2023 Nov 29 (Print Publication: 2023). - Publication Year :
- 2023
-
Abstract
- Introduction: Open Reading Frame 8 (ORF8) is a 121 amino acid length SARS-CoV-2 specific accessory protein that plays crucial roles in viral infectivity, and pathogenesis. Current SARS-CoV-2 treatments focus on spike or RNA-dependent RNA polymerase proteins. Hence, directing attention to ORF8 yields substantial benefits for innovative non-infusional therapeutics. Functional ORF8 is proposed to form oligomers via a crystallographic contact centered by 73YIDI76 motifs. Methods: Hence, the structure and atomistic interactions of trimeric and tetrameric ORF8 oligomeric forms were modeled by means of thorough molecular modeling and molecular dynamics simulations. Results: Results show that trimeric and tetrameric oligomers are stabilized by the interaction of β4-β5 (47-83) loops. 73YIDI76 motifs are involved in obtaining the oligomerization interfaces. It is shown that the tetramers which resemble a doughnut-like construction are the most stabilized oligomeric forms. Where four β4-β5 loops form the interfaces between two dimers. Each monomer links to two others through β4-β5 loops and a covalent Cys20-Cys20 bridge. Epitope mapping, binding site predictions, and solvent-accessible surface area analyses of different ORF8 forms show that the B-cell, MHC-I, and drug epitopes stay exposed in oligomeric forms. Discussion: Approving that the viral infectivity is expanded upon ORF8 oligomerization and the regions involved in oligomerization can be considered as therapeutic targets.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2023 Assadizadeh and Azimzadeh Irani.)
Details
- Language :
- English
- ISSN :
- 2296-889X
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Frontiers in molecular biosciences
- Publication Type :
- Academic Journal
- Accession number :
- 38094081
- Full Text :
- https://doi.org/10.3389/fmolb.2023.1270511