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Ivermectin is a putative antiviral compound; the proposed mechanism is the inhibition of nuclear translocation of viral proteins, facilitated by mammalian host importins, a necessary process for propagation of infections. We systematically reviewed the evidence for the applicability of ivermectin against viral infections including SARS\u2010CoV\u20102 regarding efficacy, mechanisms and selective toxicity. The SARS\u2010CoV\u20102 genome was mined to determine potential nuclear location signals for ivermectin and meta\u2010analyses for<jats:italic>in vivo<\/jats:italic>studies included all comparators over time, dose range and viral replication in multiple organs. Ivermectin inhibited the replication of many viruses including those in<jats:italic>Flaviviridae<\/jats:italic>,<jats:italic>Circoviridae<\/jats:italic>and<jats:italic>Coronaviridae<\/jats:italic>families<jats:italic>in vitro<\/jats:italic>. Real and mock nuclear location signals were identified in SARS\u2010CoV\u20102, a potential target for ivermectin and predicting a sequestration bait for importin \u03b2, stopping infected cells from reaching a virus\u2010resistant state. While pharmacokinetic evaluations indicate that ivermectin could be toxic if applied based on<jats:italic>in vitro<\/jats:italic>studies, inhibition of viral replication<jats:italic>in vivo<\/jats:italic>was shown for Porcine circovirus in piglets and Suid herpesvirus in mice. Overall standardized mean differences and 95% confidence intervals for ivermectin versus controls were \u22124.43 (\u22125.81, \u22123.04),<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.00001. Based on current results, the potential for repurposing ivermectin as an antiviral agent is promising. However, further work is needed to reconcile<jats:italic>in vitro<\/jats:italic>studies with clinical efficacy. Developing ivermectin as an additional antiviral agent should be pursued with an emphasis on pre\u2010clinical trials in validated models of infection.<\/jats:p>","DOI":"10.1111\/fcp.12644","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T05:51:18Z","timestamp":1610689878000},"page":"260-276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A systematic review of experimental evidence for antiviral effects of ivermectin and an in silico analysis of ivermectin's possible mode of action against SARS\u2010CoV\u20102"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1166-0947","authenticated-orcid":false,"given":"Robert T.","family":"Kinobe","sequence":"first","affiliation":[{"name":"College of Public Health, Medical and Veterinary Sciences James Cook University Townsville QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Owens","sequence":"additional","affiliation":[{"name":"College of Public Health, Medical and Veterinary Sciences James Cook University Townsville QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-020-0336-z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092100"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.10.009"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks147"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20120150"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.06.002"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/8043983"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104760"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.10.004"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057110390360"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2018.09.010"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.005"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1948-7134.2009.00022.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-43"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(200006)22:6<532::AID-BIES6>3.0.CO;2-O"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240550106"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvd092"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2009.07.003"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-015-2653-2"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8030409"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006934"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquaculture.2013.11.022"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007681"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007210"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2019.01.010"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2019.03.012"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2007.00579.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104787"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01012-07"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13337-012-0084-1"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290286"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2012.00102"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01818"},{"key":"e_1_2_10_35_1","first-page":"1","article-title":"Understanding COVID\u201019 via comparative analysis of dark proteomes of SARS\u2010CoV\u20102, human SARS and bat SARS\u2010like coronaviruses","volume":"25","author":"Giri R","year":"2020","journal-title":"Cell Mol. 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