Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study

Gagan Preet; Emmanuel T. Oluwabusola; Bruce F. Milne; Rainer Ebel; Marcel Jaspars

doi:10.3390/ijms232214287

Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study

Gagan Preet, Emmanuel T. Oluwabusola, Bruce F. Milne, Rainer Ebel, Marcel Jaspars^* (Corresponding Author)

^*Corresponding author for this work

University of Coimbra

Research output: Contribution to journal › Article › peer-review

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Abstract

Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the Orthopoxvirus genus of the Poxviridae family. Monkeypox is a zoonotic disease where the primary significant hosts are rodents and non-human primates. There is an increasing global incidence with a 2022 outbreak that has spread to Europe in the middle of the COVID-19 pandemic. The new outbreak has novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involving the use of tecovirimat. However, there has otherwise been limited research interest in monkeypox. Mitoxantrone (MXN), an anthracycline derivative, an FDA-approved therapeutic for treating cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against the vaccinia virus and monkeypox virus. In this study, virtual screening, molecular docking analysis, and pharmacophore ligand-based modelling were employed on anthracene structures (1-13) closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures (2), (7), (10) and (12) show a predicted high binding potential to suppress viral replication.

Original language	English
Article number	14287
Number of pages	15
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	22
DOIs	https://doi.org/10.3390/ijms232214287
Publication status	Published - 18 Nov 2022

Bibliographical note

Acknowledgments: A sincere thanks to P.S. Oberoi (I.C.A.R, N.D.R.I., India) and Rishi Vachaspathy Astakala (Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, UK) for their constructive suggestions. Additionally, thank Nidhan Singh Oberoi and Albrn Care, India.

Funding: B.F.M. acknowledges national funds from the Portuguese FCT—Fundação para a Ciência e a Tecnologia, I.P., within the projects UIDB/04564/2020 and UIDP/04564/2020.

Data Availability Statement

Not applicable

Keywords

in silico
monkeypox
drug repurposing
epidemic
pox viruses
pharmacophore
mitoxantrone
molecular docking
zoonotic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

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title = "Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study",

abstract = "Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the Orthopoxvirus genus of the Poxviridae family. Monkeypox is a zoonotic disease where the primary significant hosts are rodents and non-human primates. There is an increasing global incidence with a 2022 outbreak that has spread to Europe in the middle of the COVID-19 pandemic. The new outbreak has novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involving the use of tecovirimat. However, there has otherwise been limited research interest in monkeypox. Mitoxantrone (MXN), an anthracycline derivative, an FDA-approved therapeutic for treating cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against the vaccinia virus and monkeypox virus. In this study, virtual screening, molecular docking analysis, and pharmacophore ligand-based modelling were employed on anthracene structures (1-13) closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures (2), (7), (10) and (12) show a predicted high binding potential to suppress viral replication.",

keywords = "in silico, monkeypox, drug repurposing, epidemic, pox viruses, pharmacophore, mitoxantrone, molecular docking, zoonotic",

author = "Gagan Preet and Oluwabusola, {Emmanuel T.} and Milne, {Bruce F.} and Rainer Ebel and Marcel Jaspars",

note = "Acknowledgments: A sincere thanks to P.S. Oberoi (I.C.A.R, N.D.R.I., India) and Rishi Vachaspathy Astakala (Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, UK) for their constructive suggestions. Additionally, thank Nidhan Singh Oberoi and Albrn Care, India. Funding: B.F.M. acknowledges national funds from the Portuguese FCT—Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia, I.P., within the projects UIDB/04564/2020 and UIDP/04564/2020.",

year = "2022",

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language = "English",

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AU - Oluwabusola, Emmanuel T.

AU - Milne, Bruce F.

AU - Ebel, Rainer

AU - Jaspars, Marcel

N1 - Acknowledgments: A sincere thanks to P.S. Oberoi (I.C.A.R, N.D.R.I., India) and Rishi Vachaspathy Astakala (Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, UK) for their constructive suggestions. Additionally, thank Nidhan Singh Oberoi and Albrn Care, India. Funding: B.F.M. acknowledges national funds from the Portuguese FCT—Fundação para a Ciência e a Tecnologia, I.P., within the projects UIDB/04564/2020 and UIDP/04564/2020.

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N2 - Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the Orthopoxvirus genus of the Poxviridae family. Monkeypox is a zoonotic disease where the primary significant hosts are rodents and non-human primates. There is an increasing global incidence with a 2022 outbreak that has spread to Europe in the middle of the COVID-19 pandemic. The new outbreak has novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involving the use of tecovirimat. However, there has otherwise been limited research interest in monkeypox. Mitoxantrone (MXN), an anthracycline derivative, an FDA-approved therapeutic for treating cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against the vaccinia virus and monkeypox virus. In this study, virtual screening, molecular docking analysis, and pharmacophore ligand-based modelling were employed on anthracene structures (1-13) closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures (2), (7), (10) and (12) show a predicted high binding potential to suppress viral replication.

AB - Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the Orthopoxvirus genus of the Poxviridae family. Monkeypox is a zoonotic disease where the primary significant hosts are rodents and non-human primates. There is an increasing global incidence with a 2022 outbreak that has spread to Europe in the middle of the COVID-19 pandemic. The new outbreak has novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involving the use of tecovirimat. However, there has otherwise been limited research interest in monkeypox. Mitoxantrone (MXN), an anthracycline derivative, an FDA-approved therapeutic for treating cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against the vaccinia virus and monkeypox virus. In this study, virtual screening, molecular docking analysis, and pharmacophore ligand-based modelling were employed on anthracene structures (1-13) closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures (2), (7), (10) and (12) show a predicted high binding potential to suppress viral replication.

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KW - monkeypox

KW - drug repurposing

KW - epidemic

KW - pox viruses

KW - pharmacophore

KW - mitoxantrone

KW - molecular docking

KW - zoonotic

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JF - International Journal of Molecular Sciences

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ER -

Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study

Abstract

Bibliographical note

Data Availability Statement

Keywords

UN SDGs

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