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. 2023 Jan-Mar;24(1):1-12.
doi: 10.1016/j.vacun.2022.10.006. Epub 2022 Nov 4.

Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein

Ali Adel Dawood  1
Affiliations

Determination of binding affinity of tunicamycin with SARS-CoV-2 proteins: Proteinase, protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, envelope and RBD of spike glycoprotein

Ali Adel Dawood. Vacunas. 2023 Jan-Mar.

Abstract
in English, Spanish

Introduction: Despite the availability of several COVID-19 vaccines, the incidence of infections remains a serious issue. Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins.

Objectives: Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD of spike glycoprotein). Methods: Several types of chemo and bioinformatics tools were used to achieve the aim of the study. As a result, virion's effectiveness may be impaired.

Results: TM can bind to viral proteins with various degrees of affinity. The proteinase had the highest binding affinity with TM. Proteins (ORF9b, ORF8, nsp9, and RBD) were affected by unfavorable donor or acceptor bonds that impact the degree of docking. ORF7a had the weakest affinities.

Conclusions: This antibiotic is likely to effect on SARS-CoV-2 in clinical studies.

Introducción: A pesar de la disponibilidad de varias vacunas contra la COVID-19, la incidencia de infecciones sigue siendo un problema grave. La tunicamicina (TM), un antibiótico, inhibió el crecimiento tumoral, redujo la síntesis de la subunidad 2 de la glicoproteína de la envoltura del coronavirus y disminuyó la glicosilación ligada a N de las glicoproteínas del coronavirus.

Objetivos: Nuestro estudio tuvo como objetivo determinar cómo interactúa la tunicamicina con ciertas proteínas del coronavirus (proteinasa, proteasa, nsp9, ORF7a, ORF3a, ORF9b, ORF8, proteína de la envoltura, nsp2 y RBD de glicoproteína de punta).

Métodos: Se utilizaron varios tipos de herramientas de quimioterapia y bioinformática para lograr el objetivo del estudio. Como resultado, la eficacia del virión puede verse afectada.

Resultados: La TM puede unirse a proteínas virales con diversos grados de afinidad. La proteinasa tenía la mayor afinidad de unión con TM. Las proteínas (ORF9b, ORF8, nsp9 y RBD) se vieron afectadas por enlaces donantes o aceptores desfavorables que afectan el grado de acoplamiento. ORF7a tenía las afinidades más débiles.

Conclusiones: Es probable que este antibiótico tenga efecto sobre el SARS-CoV-2 en estudios clínicos.

Keywords: COVID-19; Docking; Envelope; Spike; Tunicamycin.

PubMed Disclaimer

Conflict of interest statement

There is no conflict of interest in this work.

Figures

Fig 1
Fig 1
A: Chemical structure of tunicamycin. B: crystal structure of TM. C: 3D structure of TM after docking with a protein.
Fig 2
Fig 2
Molecular docking of 1P9S-TM. A: 2D interaction shows types of fusion in specific residues. B: Crystal structure of proteinase (1P9S) shows the interaction location with TM. C: Molecular docking residues of 1P9S-TM, residues of conventional hydrogen bond (green), residues of carbon-hydrogen bond (cyan), and alkyl residues (magenta).
Fig 3
Fig 3
Molecular docking of 1Q2W-TM. A: 2D interaction shows types of fusion in specific residues. B: Crystal structure of protease (1Q2W) shows the interaction location with TM. C: Molecular docking residues of 1Q2W-TM, residues of conventional hydrogen bond (green), residues of carbon-hydrogen bond (cyan), alkyl residues (magenta), and unfavorable acceptor bound (red).
Fig 4
Fig 4
Molecular docking of 1QZ8-TM. A: 2D interaction shows types of fusion in specific residues. B: The crystal structure of nsp9 (1QZ8) shows the interaction location with TM. C: Molecular docking residues of 1QZ8-TM, residues of conventional hydrogen bond (green), residues of carbon-hydrogen bond (cyan), alkyl residues (magenta), pi-donor hydrogen bond (dark cyan), and unfavorable acceptor or donor bond (red).
Fig 5
Fig 5
Molecular docking of 1XAK-TM. A: 2D interaction shows types of fusion in specific residues. B: The crystal structure of ORF7a (1XAK) shows the interaction location with TM. C: Molecular docking residues of 1XAK-TM, residues of conventional hydrogen bond (green), residues of carbon-hydrogen bond (cyan), alkyl, and pi-alkyl residues (magenta), and pi-sulfur bond (pale orange).
Fig 6
Fig 6
Molecular docking of 6XDC-TM. A: 2D interaction shows types of fusion in specific residues. B: The crystal structure of ORF3a (6XDC) shows the interaction location with TM. C: Molecular docking residues of 6XDC-TM, residues of conventional hydrogen bond (green), residues of carbon-hydrogen bond (cyan), alkyl residues (magenta), pi-alkyl bond (dark magenta), and pi-pi-stacked bound (red).
Fig 7
Fig 7
Molecular docking of 7DHG-TM. A: 2D interaction shows types of fusion in specific residues. B: The crystal structure of ORF9b (7DHG) shows the interaction location with TM. C: Molecular docking residues of 7DHG-TM, residues of conventional hydrogen bond (green), residues of carbon-hydrogen bond (cyan), alkyl, and pi-alkyl residues (magenta), and unfavorable acceptor bond (red).
Fig 8
Fig 8
Molecular docking of 7JX6-TM. A: 2D interaction shows types of fusion in specific residues. B: The crystal structure of ORF8 (7JX6) shows the interaction location with TM. C: Molecular docking residues of 7JX6-TM, residues of conventional hydrogen bond (green), alkyl residues (magenta), and unfavorable donor residue (red).
Fig 9
Fig 9
Molecular docking of 7K3G-TM. A: 2D interaction shows types of fusion in specific residues. B: The crystal structure of envelope protein (7K3G) shows the interaction location with TM. C: Molecular docking residues of 7K3G-TM, residues of conventional hydrogen bond (green), residues of carbon-hydrogen bond (cyan), and alkyl and pi-alkyl residues (magenta).
Fig 10
Fig 10
A: The surface structure of pentameric envelope glycoprotein (7K3G). B: The molecular docking of 7K3G-TM.
Fig 11
Fig 11
Molecular docking of 7MSW-TM. A: 2D interaction shows types of fusion in specific residues. B: Crystal structure of nsp2 (7MSW) shows the interaction location with TM. C: Molecular docking residues of 7MSW-TM, residues of conventional hydrogen bond (green), residues of carbon-hydrogen bond (cyan), and alkyl and pi-alkyl residues (magenta).
Fig 12
Fig 12
Molecular docking of RBD (6M0J)-TM. A: 2D interaction shows types of fusion in specific residues. B: Crystal structure of RBD of spike glycoprotein (6M0J) shows the interaction location with TM. C: Molecular docking residues of RBD (6M0J)-TM, residues of conventional hydrogen bond (green), unfavorable donor residue (red), and alkyl and pi-alkyl residues (magenta).
Fig 13
Fig 13
Molecular docking of TM-RBD-ACE2. A: Cartoon structure of molecular docking of RBD-ACE2 (7K3G). B: Cartoon structure of the molecular docking of 7K3G-TM. C: The surface structure of 7K3G and TM shows the interaction residues of TM with RBD, hydrogen bond (green), unfavorable donor residue (red), and alkyl and pi-alkyl residues (magenta).
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