{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T03:18:38Z","timestamp":1768879118340,"version":"3.49.0"},"reference-count":41,"publisher":"SAGE Publications","issue":"5-6","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antivir Chem Chemother"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p> Chemotherapy is an important tool for controlling enterovirus infections, but clinically effective anti-enterovirus drugs do not currently exist, mainly due to the development of drug resistance. We investigated the combination effects of enterovirus replication inhibitors in order to limit this process. In previous studies, we showed the efficacy of consecutive alternating administration of the triple combinations disoxaril\/guanidine\/oxoglaucine and pleconaril\/guanidine\/oxoglaucine against coxsackievirus B1 infection in newborn mice. Drug sensitivity tests of the viral brain isolates showed that these drug combinations prevented the development of drug resistance. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> In the current study, we replaced guanidine-HCl with enteroviral RNA synthesis inhibitor MDL-860 to test the effect of a new triple combination\u2014pleconaril\/MDL-860\/oxoglaucine\u2014applied via consecutive alternating administration in newborn mice infected subcutaneously with 20 MLD<jats:sub>50<\/jats:sub> of coxsackievirus B1. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> The pleconaril\/MDL-860\/oxoglaucine combination via consecutive alternating administration showed high activity at the 75\u2009mg\/kg MDL-860 dose: a protective effect of 50% and a pronounced suppression of brain virus titers. Moreover, along with prevention of drug resistance, a phenomenon of increased drug sensitivity was established. MDL-860 sensitivity in pleconaril\/MDL-860\/oxoglaucine increased 8.2 times vs. placebo (29 times vs. monotherapy) on day 7 and oxoglaucine sensitivity\u20144.9 times vs. placebo (by 6.8 times vs. monotherapy) on day 13. As concerns pleconaril, a demonstrable prevention of drug resistance was registered without increase of drug sensitivity. Daily, simultaneous administration of pleconaril\/MDL-860\/oxoglaucine showed no protective effects and led to a rapid development of drug resistance. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p> These results add new support for using consecutive alternating administration treatment courses to achieve clinically effective chemotherapy of enterovirus infections. <\/jats:p><\/jats:sec>","DOI":"10.1177\/2040206616671571","type":"journal-article","created":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T01:19:38Z","timestamp":1478308778000},"page":"136-147","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Anti-enteroviral triple combination of viral replication inhibitors: activity against coxsackievirus B1 neuroinfection in mice"],"prefix":"10.1177","volume":"24","author":[{"given":"Adelina","family":"Stoyanova","sequence":"first","affiliation":[{"name":"Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivanka","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"P\u00fcrstinger","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgi","family":"Dobrikov","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Philipov","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angel S","family":"Galabov","sequence":"additional","affiliation":[{"name":"Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,11,4]]},"reference":[{"key":"bibr1-2040206616671571","first-page":"839","volume-title":"Fields virology","volume":"1","author":"Pallansch M","year":"2005","edition":"5"},{"key":"bibr2-2040206616671571","first-page":"1","volume":"15","author":"Khetsuriani N","year":"2006","journal-title":"MMWR Surveill Summ"},{"key":"bibr3-2040206616671571","unstructured":"Non-Polio Enteroviruses. Centers for Disease Control and Prevention. National Center for Immunization and Respiratory Diseases (NCIRD). Division of viral diseases, www.cdc.gov\/non-polio-enterovirus\/index.html (accessed 10 May 2013)."},{"key":"bibr4-2040206616671571","doi-asserted-by":"publisher","DOI":"10.7883\/yoken.52.12"},{"key":"bibr5-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909233411301"},{"key":"bibr6-2040206616671571","first-page":"798","volume":"63","author":"Midgley CM","year":"2014","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"bibr7-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1128\/9781555818326.ch1"},{"key":"bibr8-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-373741-0.50006-4"},{"key":"bibr9-2040206616671571","first-page":"201","volume":"3","author":"Duarte EA","year":"1994","journal-title":"Infect Agents Dis"},{"key":"bibr10-2040206616671571","first-page":"3","volume":"323","author":"Domingo E","year":"2008","journal-title":"Curr Top Microbiol Immunol"},{"key":"bibr11-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-68-11-2729"},{"key":"bibr12-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1656(95)00088-7"},{"key":"bibr13-2040206616671571","first-page":"47","volume-title":"New trends of microbiology (65th Anniversary of the Stephan Angeloff Institute of Microbiology)","author":"Galabov AS","year":"2012"},{"key":"bibr14-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304923"},{"key":"bibr15-2040206616671571","unstructured":"Conclusions and recommendations of the Advisory Committee on Poliomyelitis Eradication, Geneva, Part II. Wkly Epidemiol Rec 2006; 81: 465\u2013468."},{"key":"bibr16-2040206616671571","volume-title":"Committee on Development of a Polio Antiviral and Its Potential Role in Global Poliomyelitis Eradication","author":"Workshop Report","year":"2006"},{"key":"bibr17-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1769"},{"key":"bibr18-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2003.11.001"},{"key":"bibr19-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1977.tb21997.x"},{"key":"bibr20-2040206616671571","doi-asserted-by":"publisher","DOI":"10.5560\/ZNC.2011.66c0627"},{"key":"bibr21-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2009.11.003"},{"key":"bibr22-2040206616671571","doi-asserted-by":"crossref","unstructured":"Vassileva-Pencheva R and Galabov AS. Effectiveness of the consecutive alternative administration course of a triple antiviral combination in coxsakievirus B3 infections in mice. Drug Res 2016; 16: 1\u20135.","DOI":"10.1055\/s-0042-112970"},{"key":"bibr23-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.07.004"},{"key":"bibr24-2040206616671571","first-page":"287","volume-title":"Selective inhibitors of viral function","author":"Caliguiri LA","year":"1973"},{"key":"bibr25-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.07.099"},{"key":"bibr26-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.10570"},{"key":"bibr27-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.38.8.747"},{"key":"bibr28-2040206616671571","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-107-26560"},{"key":"bibr29-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1128\/AM.9.1.66-72.1961"},{"key":"bibr30-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1021\/jm00153a020"},{"key":"bibr31-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.46.100192.003223"},{"key":"bibr32-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.11.8482-8489.1997"},{"key":"bibr33-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.22.4.635"},{"key":"bibr34-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.22.4.639"},{"key":"bibr35-2040206616671571","first-page":"52","volume":"43","author":"Kuzmanov BA","year":"1998","journal-title":"Fitologia"},{"key":"bibr36-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-569-5_21"},{"key":"bibr37-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1111\/1348-0421.12261"},{"key":"bibr38-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1021\/jm00008a014"},{"key":"bibr39-2040206616671571","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(02)00277-3"},{"key":"bibr40-2040206616671571","unstructured":"Clinical Trials.gov. U.S. National Institutes of Health. Effects of pleconaril nasal spray on common cold symptoms and asthma exacerbations following rhinovirus exposure (Study P04295), https:\/\/clinicaltrials.gov\/ct\/gui\/show\/NCT00394914 (accessed 23 June 2015)."},{"key":"bibr41-2040206616671571","unstructured":"Clinical Trials.gov. U.S. National Institutes of Health. A phase 2 multicenter, randomized, double-blind, placebo-controlled study of BTA798 in asthmatic adults with symptomatic human rhinovirus infection, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01175226 (accessed 12 September 2013)."}],"container-title":["Antiviral Chemistry and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2040206616671571","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/2040206616671571","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2040206616671571","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T01:24:30Z","timestamp":1727659470000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/2040206616671571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":41,"journal-issue":{"issue":"5-6","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1177\/2040206616671571"],"URL":"https:\/\/doi.org\/10.1177\/2040206616671571","relation":{},"ISSN":["0956-3202","2040-2066"],"issn-type":[{"value":"0956-3202","type":"print"},{"value":"2040-2066","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]}}}