Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study
Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the <i>Orthopoxvirus</i> 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 wit...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14287 |
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| author | Gagan Preet Emmanuel T. Oluwabusola Bruce Forbes Milne Rainer Ebel Marcel Jaspars |
| author_facet | Gagan Preet Emmanuel T. Oluwabusola Bruce Forbes Milne Rainer Ebel Marcel Jaspars |
| author_sort | Gagan Preet |
| collection | DOAJ |
| description | Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the <i>Orthopoxvirus</i> 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 <b>(1-13)</b> closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures <b>(2)</b>, <b>(7)</b>, <b>(10)</b> and <b>(12)</b> show a predicted high binding potential to suppress viral replication. |
| first_indexed | 2024-03-09T18:16:27Z |
| format | Article |
| id | doaj.art-2d03b9eba9b64b349bca6d1c12428801 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:16:27Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2d03b9eba9b64b349bca6d1c124288012023-11-24T08:41:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221428710.3390/ijms232214287Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore StudyGagan Preet0Emmanuel T. Oluwabusola1Bruce Forbes Milne2Rainer Ebel3Marcel Jaspars4Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UKMarine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UKMarine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UKMarine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UKMarine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UKMonkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the <i>Orthopoxvirus</i> 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 <b>(1-13)</b> closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures <b>(2)</b>, <b>(7)</b>, <b>(10)</b> and <b>(12)</b> show a predicted high binding potential to suppress viral replication.https://www.mdpi.com/1422-0067/23/22/14287in silicomonkeypoxdrug repurposingepidemicpoxvirusespharmacophore |
| spellingShingle | Gagan Preet Emmanuel T. Oluwabusola Bruce Forbes Milne Rainer Ebel Marcel Jaspars Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study International Journal of Molecular Sciences in silico monkeypox drug repurposing epidemic poxviruses pharmacophore |
| title | Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study |
| title_full | Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study |
| title_fullStr | Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study |
| title_full_unstemmed | Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study |
| title_short | Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study |
| title_sort | computational repurposing of mitoxantrone related structures against monkeypox virus a molecular docking and 3d pharmacophore study |
| topic | in silico monkeypox drug repurposing epidemic poxviruses pharmacophore |
| url | https://www.mdpi.com/1422-0067/23/22/14287 |
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