{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:04:25Z","timestamp":1790190265373,"version":"4.1.0"},"reference-count":22,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Farmak Public Joint Stock Company, Kiev, Ukraine"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antivir Chem Chemother"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p> New therapeutics for the control of influenza virus infections are needed to alleviate the burden caused by seasonal epidemics and occasional pandemics, and to overcome the potential risk of drug-resistance emergence. Enisamium iodide (Amizon\u00ae, Farmak) is currently approved for clinical use for the treatment of influenza in 11 countries which includes Ukraine, Russia, Belarus, Kazakhstan, and Uzbekistan. However, experimental evidence of the antiviral activity of enisamium has not been reported. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> Antiviral activity of enisamium was assessed by virus yield reduction assays using differentiated normal human bronchial epithelial cells. Permeability of enisamium into differentiated normal human bronchial epithelial cells and its cytotoxicity were also assessed, and comparisons with other cell lines were made. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Enisamium inhibited replication of multiple subtypes of influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1, seasonal H3N2, the zoonotic H5N1 and H7N9, neuraminidase inhibitor-resistant variant carrying the H275Y NA substitution (N1 numbering), and influenza B virus at doses 23- to 64-fold lower than cytotoxic concentrations. The permeability of enisamium in Madin\u2013Darby canine kidney cells (where no antiviral activity was found) was less than 0.08%, while higher permeability was observed in differentiated normal human bronchial epithelial cells (1.9%). The kinetics of enisamium intracellular uptake in differentiated normal human bronchial epithelial cells was concentration dependent. In time-of-addition experiments in differentiated normal human bronchial epithelial cells, enisamium treatment within 4\u2009h after A(H1N1) virus inoculation resulted in 100-fold or greater reductions in virus titers, suggesting that it affects an early stage of the virus life cycle. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p> Enisamium exhibits antiviral activity against influenza viruses in vitro, supporting the reported clinical efficacy against influenza virus infections. <\/jats:p><\/jats:sec>","DOI":"10.1177\/2040206618811416","type":"journal-article","created":{"date-parts":[[2018,11,23]],"date-time":"2018-11-23T01:35:00Z","timestamp":1542936900000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Activity of enisamium, an isonicotinic acid derivative, against influenza viruses in differentiated normal human bronchial epithelial cells"],"prefix":"10.1177","volume":"26","author":[{"given":"David","family":"Boltz","sequence":"first","affiliation":[{"name":"Illinois Institute of Technology Research Institute, Chicago, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjian","family":"Peng","sequence":"additional","affiliation":[{"name":"Illinois Institute of Technology Research Institute, Chicago, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Muzzio","sequence":"additional","affiliation":[{"name":"Illinois Institute of Technology Research Institute, Chicago, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradyot","family":"Dash","sequence":"additional","affiliation":[{"name":"St Jude Children\u2019s Research Hospital, Memphis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G","family":"Thomas","sequence":"additional","affiliation":[{"name":"St Jude Children\u2019s Research Hospital, Memphis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Margitich","sequence":"additional","affiliation":[{"name":"Farmak Public Joint Stock Company, Kiev, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,11,22]]},"reference":[{"key":"bibr1-2040206618811416","first-page":"187","volume":"6","author":"Kamali A","year":"2013","journal-title":"Infect Drug Resist"},{"key":"bibr2-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp0900648"},{"key":"bibr3-2040206618811416","unstructured":"World Health Organization (WHO). Weekly epidemiological record, no. 44\u201345, 477\u2013488, http:\/\/www.who.int\/wer\/2013\/wer8844_45.pdf?ua=1 (2013, accessed February 2018)."},{"key":"bibr4-2040206618811416","unstructured":"Centers for Disease Control and Prevention. 2017\u20132018 influenza season week 2 ending January 13. Antiviral resistance, https:\/\/www.cdc.gov\/flu\/weekly\/ (2018, accessed February 2018)."},{"key":"bibr5-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01067-13"},{"key":"bibr6-2040206618811416","doi-asserted-by":"crossref","unstructured":"Takashita E, Ejima M, Itoh Ret\u00a0al. A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November to December 2013. Euro Surveill 2014; 19: 1\u20136.","DOI":"10.2807\/1560-7917.ES2014.19.1.20666"},{"key":"bibr7-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis337"},{"key":"bibr8-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0910448"},{"key":"bibr9-2040206618811416","unstructured":"Zhebrovska F, Margitych V, Kostiuk G, et\u00a0al. Alpha-crystalline form of carbabenzpyride. Patent 8,404,857 B2, USA, 2013."},{"key":"bibr10-2040206618811416","unstructured":"Okhapkina \u0415\u0410, Melnikova \u0422I, Deeva EGet\u00a0al. A prospective single-blind comparative clinical study of efficacy and safety of Amizon 0.25 g tablets manufactured by Farmak JSC in patients with influenza and influenza like illness. Report of Research Institute of Influenza of North-West Branch of Russian Academy of Medical Sciences (NWB RAMS), 2010, p.1\u201361."},{"key":"bibr11-2040206618811416","doi-asserted-by":"publisher","DOI":"10.4149\/av_2018_211"},{"key":"bibr12-2040206618811416","first-page":"493","volume":"27","author":"Reed LJ","year":"1938","journal-title":"Am J Hyg"},{"key":"bibr13-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075014"},{"key":"bibr14-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2004.03.011"},{"key":"bibr15-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021183"},{"key":"bibr16-2040206618811416","first-page":"1647","volume-title":"Fields\u2019 virology","author":"Shaw ML","year":"2011"},{"key":"bibr17-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2016.11.008"},{"key":"bibr18-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308001101"},{"key":"bibr19-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.3.981-986.2005"},{"key":"bibr20-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101143108"},{"key":"bibr21-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp393"},{"key":"bibr22-2040206618811416","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00888-16"}],"container-title":["Antiviral Chemistry and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2040206618811416","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/2040206618811416","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2040206618811416","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T02:55:50Z","timestamp":1728442550000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/2040206618811416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":22,"alternative-id":["10.1177\/2040206618811416"],"URL":"https:\/\/doi.org\/10.1177\/2040206618811416","relation":{},"ISSN":["0956-3202","2040-2066"],"issn-type":[{"value":"0956-3202","type":"print"},{"value":"2040-2066","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]},"article-number":"2040206618811416"}}