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Previous vaccinia virus vaccination can protect from monkeypox. However, after smallpox eradication, immunization against that was stopped. Indeed, therapeutic options following the disease onset are of great value. This study aimed to review the available evidence on virology and treatment approaches for monkeypox and provide guidance for patient care and future studies. Since no randomized clinical trials were ever performed, we reviewed monkeypox animal model studies and clinical trials on the safety and pharmacokinetics of available medications. Brincidofovir and tecovirimat were the most studied medications that got approval for smallpox treatment according to the Animal Rule. Due to the conserved virology among\n                    <jats:italic>Orthopoxviruses<\/jats:italic>\n                    , available medications might also be effective against monkeypox. However, tecovirimat has the strongest evidence to be effective and safe for monkeypox treatment, and if there is a choice between the two drugs, tecovirimat has shown more promise so far. The risk of resistance should be considered in patients who failed to respond to tecovirimat. Hence, the target\u2010based design of novel antivirals will enhance the availability and spectrum of effective anti\u2010\n                    <jats:italic>Orthopoxvirus<\/jats:italic>\n                    agents.\n                  <\/jats:p>","DOI":"10.1002\/jmv.28229","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:23:26Z","timestamp":1666052606000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Monkeypox treatment: Current evidence and future perspectives"],"prefix":"10.1002","volume":"95","author":[{"given":"Elnaz","family":"Khani","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bentelhoda","family":"Afsharirad","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3653-3653","authenticated-orcid":false,"given":"Taher","family":"Entezari\u2010Maleki","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy Tabriz University of Medical Sciences Tabriz Iran"},{"name":"Cardiovascular Research Center Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization. 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