Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactions
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1270511/full |
| _version_ | 1797448634843791360 |
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| author | Mohammad Assadizadeh Maryam Azimzadeh Irani |
| author_facet | Mohammad Assadizadeh Maryam Azimzadeh Irani |
| author_sort | Mohammad Assadizadeh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T14:13:15Z |
| format | Article |
| id | doaj.art-edc7626ad4274a61953ac25336ff5c3d |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-09T14:13:15Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-edc7626ad4274a61953ac25336ff5c3d2023-11-29T05:53:35ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-11-011010.3389/fmolb.2023.12705111270511Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactionsMohammad AssadizadehMaryam Azimzadeh IraniIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1270511/fullSARS-CoV-2ORF8oligomerizationmolecular modelingmolecular dynamicsB-cell |
| spellingShingle | Mohammad Assadizadeh Maryam Azimzadeh Irani Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactions Frontiers in Molecular Biosciences SARS-CoV-2 ORF8 oligomerization molecular modeling molecular dynamics B-cell |
| title | Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactions |
| title_full | Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactions |
| title_fullStr | Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactions |
| title_full_unstemmed | Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactions |
| title_short | Oligomer formation of SARS-CoV-2 ORF8 through 73YIDI76 motifs regulates immune response and non-infusion antiviral interactions |
| title_sort | oligomer formation of sars cov 2 orf8 through 73yidi76 motifs regulates immune response and non infusion antiviral interactions |
| topic | SARS-CoV-2 ORF8 oligomerization molecular modeling molecular dynamics B-cell |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1270511/full |
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