{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:06:19Z","timestamp":1790823979334,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Monkeypox infection is caused by a virus of the genus Orthopoxvirus, a member of the Poxviridae family. Monkeypox virus is transmitted from individual to individual through contact with lesions, body fluids, and respiratory droplets. The infection caused by monkeypox is usually a self-limited disease with mild symptoms lasting 2 to 4 weeks. Monkeypox typically presents with fever, rash, and enlarged lymph nodes. New vaccines have recently been authorized for the prevention of monkeypox infection, whereas there are no specific pharmacological antiviral treatments for monkeypox infection. However, because the viruses which cause adult smallpox and monkeypox are similar, antiviral drugs developed in the past have also shown efficacy against monkeypox. In this review, we highlight the in vitro and clinical evidence found in the literature on the efficacy and safety of pharmacological agents with antiviral activity against monkeypox infection and the different regulatory aspects of countries.<\/jats:p>","DOI":"10.3390\/ijms232415941","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T01:52:30Z","timestamp":1671069150000},"page":"15941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pharmacological Agents with Antiviral Activity against Monkeypox Infection"],"prefix":"10.3390","volume":"23","author":[{"given":"Andrea","family":"Zovi","sequence":"first","affiliation":[{"name":"Ministry of Health, Viale Giorgio Ribotta 5, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9298-6783","authenticated-orcid":false,"given":"Francesco","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Asl Napoli 3 Sud, Pharmaceutical Department, Dell\u2019amicizia Street 22, 80035 Nola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Langella","sequence":"additional","affiliation":[{"name":"Italian Society of Hospital Pharmacy (SIFO), SIFO Secretariat of the Lombardy Region, Via Carlo Farini 81, 20159 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Vitiello","sequence":"additional","affiliation":[{"name":"Ministry of Health, Viale Giorgio Ribotta 5, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","first-page":"94","article-title":"Epidemiology, diagnosis, and control of monkeypox disease: A comprehensive review","volume":"5","author":"Pal","year":"2017","journal-title":"Am. J. Infect. Dis. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/01652176.2022.2086718","article-title":"Appearance and re-appearance of zoonotic disease during the pandemic period: Long-term monitoring and analysis of zoonosis is crucial to confirm the animal origin of SARS-CoV-2 and monkeypox virus","volume":"42","author":"Chakraborty","year":"2022","journal-title":"Veter Q."},{"key":"ref_3","unstructured":"(2022, June 01). Multi-Country Monkeypox Outbreak in Non-Endemic Countries. Available online: https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13010-022-00116-2","article-title":"The \u201cOne Health\u201d approach in the face of COVID-19: How radical should it be?","volume":"17","author":"Sironi","year":"2022","journal-title":"Philos. Ethic Humanit. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Alakunle, E., Moens, U., Nchinda, G., and Okeke, M. (2020). Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution. Viruses, 12.","DOI":"10.3390\/v12111257"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s00210-022-02265-9","article-title":"Pandemic COVID-19, an update of current status and new therapeutic strategies","volume":"395","author":"Vitiello","year":"2022","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1007\/s10787-022-01055-2","article-title":"Nirmatrelvir\u2013remdesivir association for non-hospitalized adults with COVID-19, point of view","volume":"30","author":"Ferrara","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ref_8","unstructured":"(2021, July 27). Available online: https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/monkeypox---the-united-states-of-america."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1128\/jvi.62.10.3772-3778.1988","article-title":"Vaccinia virus gene D8 encodes a virion transmembrane protein","volume":"62","author":"Niles","year":"1988","journal-title":"J. Virol."},{"key":"ref_10","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_11","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_12","unstructured":"(2022, June 01). Monkeypox\u2014United Kingdom of Great Britain and Northern Ireland (Nigeria). 11 June 2021. Available online: https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/monkeypox---united-kingdom-of-great-britain-and-northern-ireland."},{"key":"ref_13","unstructured":"World Health Organization (2022, June 01). Monkeypox\u2014United Kingdom of Great Britain and Northern Ireland. 8 July 2021. Available online: https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/monkeypox---united-kingdom-of-great-britain-and-northern-ireland."},{"key":"ref_14","unstructured":"Nigeria Centre for Disease Control (2022, June 01). Monkeypox Situation Report in Nigeria. 31 May 2021. Available online: https:\/\/reliefweb.int\/report\/nigeria\/may-2021-monkeypox-situation-report-nigeria-epi-week-21-may-31-2021."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"638","DOI":"10.2471\/BLT.19.242347","article-title":"Modelling human-to-human transmission of monkeypox","volume":"98","author":"Grant","year":"2020","journal-title":"Bull. World Heal. Organ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s11845-021-02584-5","article-title":"COVID-19 pandemic: Vaccine and new monoclonal antibodies, point of view","volume":"191","author":"Vitiello","year":"2022","journal-title":"Ir. J. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103630","DOI":"10.1016\/j.jri.2022.103630","article-title":"Pregnancy and COVID-19, focus on vaccine and pharmacological treatment","volume":"151","author":"Vitiello","year":"2022","journal-title":"J. Reprod. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101710","DOI":"10.1016\/j.eclinm.2022.101710","article-title":"Global monkeypox case hospitalisation rates: A rapid systematic review and meta-analysis","volume":"54","author":"DeWitt","year":"2022","journal-title":"Eclinicalmedicine"},{"key":"ref_19","unstructured":"Food and Drug Administration (2022, June 01). Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-drug-indication-treatment-smallpox."},{"key":"ref_20","unstructured":"Italian Medicines Agency (2022, July 22). Available online: https:\/\/www.aifa.gov.it\/documents\/20142\/1621464\/2022.07.25_com_EMA_raccomandazione_Imvanex_vaiolo_scimmie_IT.pdf."},{"key":"ref_21","first-page":"114","article-title":"Antirheumatic in SARS-CoV-2: Benefit or risk?","volume":"14","author":"Ferrara","year":"2020","journal-title":"Ital. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1097\/00042560-199700001-00006","article-title":"Clinical Experience With Cidofovir in the Treatment of Cytomegalovirus Retinitis","volume":"14","author":"Lalezari","year":"1997","journal-title":"J. Acquir. Immune Defic. Syndr. Hum. Retrovirology"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kuroda, N., Shimizu, T., Hirano, D., Ishikane, M., and Kataoka, Y. (2022). Lack of clinical evidence of antiviral therapy for human monkeypox: A scoping review. J. Infect. Chemother.","DOI":"10.1016\/j.jiac.2022.10.009"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ortiz-Saavedra, B., Le\u00f3n-Figueroa, D.A., Montes-Madariaga, E.S., Ricardo-Mart\u00ednez, A., Alva, N., Cabanillas-Ramirez, C., and Rodriguez-Morales, A.J. (2022). Antiviral Treatment against Monkeypox: A Scoping Review. Trop. Med. Infect. Dis., 7.","DOI":"10.3390\/tropicalmed7110369"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.3390\/v2122803","article-title":"Cidofovir Activity against Poxvirus Infections","volume":"2","author":"Andrei","year":"2010","journal-title":"Viruses"},{"key":"ref_26","unstructured":"Food and Drug Administration (2021, April 06). Available online: https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-drug-treat-smallpox."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5570","DOI":"10.1128\/AAC.02814-14","article-title":"In Vitro Efficacy of Brincidofovir against Variola Virus","volume":"58","author":"Olson","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/jac\/dku545","article-title":"ST-246 is a key antiviral to inhibit the viral F13L phospholipase, one of the essential proteins for orthopoxvirus wrapping","volume":"70","author":"Duraffour","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/S1473-3099(22)00228-6","article-title":"Clinical features and management of human monkeypox: A retrospective observational study in the UK","volume":"22","author":"Adler","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4103\/ijp.IJP_417_20","article-title":"Are multiple sclerosis therapies safe in severe acute respiratory syndrome coronavirus 2 times?","volume":"52","author":"Ferrara","year":"2020","journal-title":"Indian J. Pharmacol."},{"key":"ref_31","first-page":"2129","article-title":"Poxviridae","volume":"Volume 2","author":"Knipe","year":"2013","journal-title":"Fields Virology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e0149521","DOI":"10.1128\/mBio.01495-21","article-title":"Ancient Gene Capture and Recent Gene Loss Shape the Evolution of Orthopoxvirus-Host Interaction Genes","volume":"12","author":"Senkevich","year":"2021","journal-title":"mBio"},{"key":"ref_33","first-page":"2160","article-title":"Poxviruses","volume":"Volume 2","author":"Knipe","year":"2013","journal-title":"Fields Virology"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gao, J., Gigante, C., Khmaladze, E., Liu, P., Tang, S., Wilkins, K., Zhao, K., Davidson, W., Nakazawa, Y., and Maghlakelidze, G. (2018). Genome Sequences of Akhmeta Virus, an Early Divergent Old World Orthopoxvirus. Viruses, 10.","DOI":"10.3390\/v10050252"},{"key":"ref_35","first-page":"165","article-title":"Human monkeypox, 1970\u201379","volume":"58","author":"Breman","year":"1980","journal-title":"Bull World Health Organ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.virol.2008.11.015","article-title":"Mousepox in the C57BL\/6 strain provides an improved model for evaluating anti-poxvirus therapies","volume":"385","author":"Parker","year":"2009","journal-title":"Virology"},{"key":"ref_37","first-page":"492","article-title":"The survival of smallpox virus (variola minor) in natural circumstances","volume":"38","author":"Wolff","year":"1968","journal-title":"Bull. World Heal. Organ."},{"key":"ref_38","first-page":"115","article-title":"The role of squirrels in sustaining monkeypox virus transmission","volume":"39","author":"Khodakevich","year":"1987","journal-title":"Trop. Geogr. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"746","DOI":"10.4269\/ajtmh.2010.09-0716","article-title":"A silent enzootic of an orthopoxvirus in Ghana, West Africa: Evidence for multi-species involvement in the absence of widespread human disease","volume":"82","author":"Reynolds","year":"2010","journal-title":"Amer. J. Tropical. Med. Hyg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.3201\/eid1009.040310","article-title":"Experimental infection of ground squirrels (Spermophilius tridecemlineatus) with Monkeypox virus","volume":"10","author":"Tesh","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"155","DOI":"10.4269\/ajtmh.2007.76.155","article-title":"Comparative pathology of north american and central african strains of monkeypox virus in a ground squirrel model of the disease","volume":"76","author":"Sbrana","year":"2007","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3201\/eid1003.030878","article-title":"Monkeypox Transmission and Pathogenesis in Prairie Dogs","volume":"10","author":"Guarner","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1354\/vp.41-6-702","article-title":"Extensive lesions of Monkeypox in a prairie dog (Cynomys sp)","volume":"41","author":"Langohr","year":"2004","journal-title":"Vet. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"539","DOI":"10.3201\/eid1104.040907","article-title":"Experimental Infection of Prairie Dogs with Monkeypox Virus","volume":"11","author":"Xiao","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1099\/vir.0.005108-0","article-title":"A prairie dog animal model of systemic orthopoxvirus disease using West African and Congo Basin strains of monkeypox virus","volume":"90","author":"Hutson","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.virol.2008.09.025","article-title":"Experimental infection of an African dormouse (Graphiurus kelleni) with monkeypox virus","volume":"383","author":"Schultz","year":"2009","journal-title":"Virology"},{"key":"ref_47","first-page":"1","article-title":"The eradication of smallpox","volume":"23","author":"Fenner","year":"1977","journal-title":"Prog. Med. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hutson, C.L., Abel, J.A., Carroll, D.S., Olson, V.A., Braden, Z.H., Hughes, C.M., Dillon, M., Hopkins, C., Karem, K.L., and Damon, I.K. (2010). Comparison of West African and Congo Basin Monkeypox Viruses in BALB\/c and C57BL\/6 Mice. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008912"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1128\/JVI.02012-09","article-title":"A Mouse Model of Lethal Infection for Evaluating Prophylactics and Therapeutics against Monkeypox Virus","volume":"84","author":"Stabenow","year":"2010","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Osorio, J.E., Iams, K.P., Meteyer, C.U., and Rocke, T.E. (2009). Comparison of Monkeypox Viruses Pathogenesis in Mice by In Vivo Imaging. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006592"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8172","DOI":"10.1128\/JVI.00621-10","article-title":"Identification of Wild-Derived Inbred Mouse Strains Highly Susceptible to Monkeypox Virus Infection for Use as Small Animal Models","volume":"84","author":"Americo","year":"2010","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/cid\/cit703","article-title":"Human monkeypox","volume":"58","author":"McCollum","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e210","DOI":"10.1093\/cid\/ciaa143","article-title":"Clinical Course and Outcome of Human Monkeypox in Nigeria","volume":"71","author":"Ogoina","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/14787210.2019.1567330","article-title":"Monkeypox re-emergence in Africa: A call to expand the concept and practice of One Health","volume":"17","author":"Reynolds","year":"2019","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nature07529","article-title":"Protein kinase R reveals an evolutionary model for defeating viral mimicry","volume":"457","author":"Elde","year":"2009","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nsmb.1529","article-title":"Rapid evolution of protein kinase PKR alters sensitivity to viral inhibitors","volume":"16","author":"Rothenburg","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"a010199","DOI":"10.1101\/cshperspect.a010199","article-title":"Poxvirus DNA replication","volume":"5","author":"Moss","year":"2013","journal-title":"Cold Spring Harb. Perspect Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1093\/molbev\/msq088","article-title":"Using Time-Structured Data to Estimate Evolutionary Rates of Double-Stranded DNA Viruses","volume":"27","author":"Firth","year":"2010","journal-title":"Mol. Biol. Evol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1016\/j.cub.2016.10.061","article-title":"17th Century Variola Virus Reveals the Recent History of Smallpox","volume":"26","author":"Duggan","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nrg2323","article-title":"Rates of evolutionary change in viruses: Patterns and determinants","volume":"9","author":"Duffy","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"msac009","DOI":"10.1093\/molbev\/msac009","article-title":"Purifying selection determines the short-term time dependency of Evolutionary Rates in SARS-CoV-2 and pH1N1 influenza","volume":"39","author":"Ghafari","year":"2022","journal-title":"Mol. Biol. Evol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7073","DOI":"10.1093\/nar\/17.17.7073","article-title":"Amplification of the ribonucleotide reductase small subunit gene: Analysis of novel joints and the mechanism of gene duplication in vaccinia virus","volume":"17","author":"Slabaugh","year":"1989","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"11576","DOI":"10.1128\/JVI.00618-14","article-title":"Duplication of the A17L Locus of Vaccinia Virus Provides an Alternate Route to Rifampin Resistance","volume":"88","author":"Erlandson","year":"2014","journal-title":"J. Virol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15941\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:33Z","timestamp":1760146893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":63,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415941"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415941","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]}}}