{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:25:50Z","timestamp":1777447550240,"version":"3.51.4"},"reference-count":28,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ortuguese FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","award":["UIDB\/04564\/2020"],"award-info":[{"award-number":["UIDB\/04564\/2020"]}]},{"name":"ortuguese FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","award":["UIDP\/04564\/2020"],"award-info":[{"award-number":["UIDP\/04564\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms232214287","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T03:29:50Z","timestamp":1668742190000},"page":"14287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7978-7306","authenticated-orcid":false,"given":"Gagan","family":"Preet","sequence":"first","affiliation":[{"name":"Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-4323","authenticated-orcid":false,"given":"Emmanuel T.","family":"Oluwabusola","sequence":"additional","affiliation":[{"name":"Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5522-4808","authenticated-orcid":false,"given":"Bruce Forbes","family":"Milne","sequence":"additional","affiliation":[{"name":"Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK"},{"name":"CFisUC, Department of Physics, University of Coimbra, Rua Larga, 3004-516 Coimbra, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9702-2235","authenticated-orcid":false,"given":"Rainer","family":"Ebel","sequence":"additional","affiliation":[{"name":"Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2426-6028","authenticated-orcid":false,"given":"Marcel","family":"Jaspars","sequence":"additional","affiliation":[{"name":"Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1086\/595552","article-title":"Transmission of atypical varicella-zoster virus infections involving palm and sole manifestations in an area with monkeypox endemicity","volume":"48","author":"MacNeil","year":"2009","journal-title":"Clin. Infect Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.meegid.2013.10.014","article-title":"Poxviruses and the evolution of host range and virulence","volume":"21","author":"Haller","year":"2014","journal-title":"Infect Genet. Evol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Brown, K., and Leggat, P.A. (2016). Human Monkeypox: Current State of Knowledge and Implications for the Future. Trop. Med. Infect Dis., 1.","DOI":"10.3390\/tropicalmed1010008"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102394","DOI":"10.1016\/j.tmaid.2022.102394","article-title":"Monkeypox virus: A novel sexually transmitted disease? A case report from France","volume":"49","author":"Vallee","year":"2022","journal-title":"Travel. Med. Infect. Dis."},{"key":"ref_5","unstructured":"Tesini, B.L. (2022, August 13). Monkeypox. Available online: https:\/\/www.msdmanuals.com\/en-sg\/professional\/infectious-diseases\/pox-viruses\/monkeypox."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.3201\/eid2608.191387","article-title":"Imported Monkeypox, Singapore","volume":"26","author":"Yong","year":"2020","journal-title":"Emerg. Infect Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1800509","DOI":"10.2807\/1560-7917.ES.2018.23.38.1800509","article-title":"Two cases of monkeypox imported to the United Kingdom, September 2018","volume":"23","author":"Vaughan","year":"2018","journal-title":"Eurosurveillance"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"980","DOI":"10.3201\/eid2505.190076","article-title":"Diagnosis of Imported Monkeypox, Israel, 2018","volume":"25","author":"Erez","year":"2019","journal-title":"Emerg. Infect Dis."},{"key":"ref_9","unstructured":"CDC (2022, June 14). U.S. Monkeypox Outbreak 2022: Situation Summary, Available online: https:\/\/stacks.cdc.gov\/view\/cdc\/118618."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"D54","DOI":"10.1016\/j.vaccine.2011.04.014","article-title":"Status of human monkeypox: Clinical disease, epidemiology and research","volume":"29","author":"Damon","year":"2011","journal-title":"Vaccine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Reynolds, M.G., McCollum, A.M., Nguete, B., Shongo Lushima, R., and Petersen, B.W. (2017). Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research. Viruses, 9.","DOI":"10.3390\/v9120380"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1212\/WNL.63.12_suppl_6.S15","article-title":"Mechanism of action of mitoxantrone","volume":"63","author":"Fox","year":"2004","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13392","DOI":"10.1128\/JVI.00770-07","article-title":"Identification of novel antipoxviral agents: Mitoxantrone inhibits vaccinia virus replication by blocking virion assembly","volume":"81","author":"Deng","year":"2007","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.antiviral.2011.12.001","article-title":"Inhibition of cowpox virus and monkeypox virus infection by mitoxantrone","volume":"93","author":"Altmann","year":"2012","journal-title":"Antivir. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yang, Q., Xia, D., Syed, A.A.S., Wang, Z., and Shi, Y. Highly accurate protein structure prediction and drug screen of monkeypox virus proteome. J. Infect., 2022.","DOI":"10.1016\/j.jinf.2022.08.006"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lam, H.Y.I., Guan, J.S., and Mu, Y. (2022). In Silico Repurposed Drugs against Monkeypox Virus. Molecules, 27.","DOI":"10.1101\/2022.07.17.500371"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"985450","DOI":"10.3389\/fimmu.2022.985450","article-title":"Multi-epitope chimeric vaccine design against emerging Monkeypox virus via reverse vaccinology techniques- a bioinformatics and immunoinformatics approach","volume":"13","author":"Aiman","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Abdi, S.A.H., Ali, A., Sayed, S.F., Ali, A., and Alam, P. (2022). Multi-Epitope-Based Vaccine Candidate for Monkeypox: An In Silico Approach. Vaccines, 10.","DOI":"10.3390\/vaccines10091564"},{"key":"ref_19","unstructured":"Fields, B.N., Chanock, R.M., Hirsch, M.S., Melnick, J., Monath, T.P., and Roizman, B. (1990). Virology, Raven Press. [2nd ed.]."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16900","DOI":"10.1073\/pnas.0804525105","article-title":"Crystal structure of poxvirus thymidylate kinase: An unexpected dimerization has implications for antiviral therapy","volume":"105","author":"Caillat","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","unstructured":"Minasov, G., Shuvalova, L., Dubrovska, I., Flores, K., Grimshaw, S., Kwon, K., Anderson, W.F., and Center for Structural Genomics of Infectious Diseases (CSGID) (2022, August 25). 1.52 Angstrom Crystal Structure of A42R Profilin-like Protein from Monkeypox Virus Zaire-96-I-16. Available online: https:\/\/www.wwpdb.org\/pdb?id=pdb_00004qwo."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8424","DOI":"10.1073\/pnas.1810398115","article-title":"Structural basis for the inhibition of poxvirus assembly by the antibiotic rifampicin","volume":"115","author":"Garriga","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D1388","DOI":"10.1093\/nar\/gkaa971","article-title":"PubChem in 2021: New data content and improved web interfaces","volume":"49","author":"Kim","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1021\/ci049885e","article-title":"LigandScout:\u20093-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters","volume":"45","author":"Wolber","year":"2005","journal-title":"J. Chem. Inf. Model"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera- a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model"},{"key":"ref_28","unstructured":"(2022, August 26). SAMSON: Software for Adaptive Modeling and Simulation Of Nanosystems. Available online: https:\/\/www.samson-connect.net."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:50Z","timestamp":1760145650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,18]]},"references-count":28,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232214287"],"URL":"https:\/\/doi.org\/10.3390\/ijms232214287","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,18]]}}}