{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:58:47Z","timestamp":1791388727564,"version":"4.3.3"},"reference-count":24,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100003336","name":"Bulgarian National Science Fund","doi-asserted-by":"publisher","award":["DN 11\/12 (18.12.2017)"],"award-info":[{"award-number":["DN 11\/12 (18.12.2017)"]}],"id":[{"id":"10.13039\/501100003336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antivir Chem Chemother"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We developed a new approach for the treatment of enterovirus infections, the consecutive alternating administration (CAA) of a combination of enterovirus inhibitors. On the model of coxsackievirus B1 (CVB1) in mice, two phenomena were observed: absence of drug resistance and increased susceptibility to the antivirals. This study aims to clarify the genetic basis of these phenomena.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Brain samples from CVB1-infected mice subjected to a CAA course with the combination pleconaril\/MDL-860\/oxoglaucine were used for viral RNA extraction and next generation sequencing. In parallel, samples from monotherapeutic courses of the three substances included in the combination were studied. Whole genome sequence analysis was carried out on all samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Samples of pleconaril monotherapy showed mutations in 5\u2032untranslated region, VP3, 2C, 3C and 2A regions of viral RNA, translated in amino acid substitution of the 2A protein. The MDL-860 course induced changes in CVB1 RNA in the VP3 and 2C regions. The oxoglaucine monotherapy samples showed RNA mutation and amino acid substitution in the VP1 region and nucleotide substitution in the 3D region. In the specimens taken from mice subjected to the CAA course with pleconaril\/MDL-860\/oxoglaucine, the following RNA mutations were established: 5\u2032 untranslated region, 2A, and 2B, and amino acids substitutions in VP3 and 2A, which differ from those mentioned above. These changes could be the reason for the prevention of drug resistance development and also to be considered as the basis for the phenomenon of increased drug susceptibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results reveal that the high anti-enteroviral efficacy of the CAA course is substantiated by the appearance of specific changes in the viral genome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/2040206620906061","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T23:39:59Z","timestamp":1581377999000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Genome analysis of coxsackievirus B1 isolates during the consecutive alternating administration course of triple antiviral combination in newborn mice"],"prefix":"10.1177","volume":"28","author":[{"given":"Petar","family":"Grozdanov","sequence":"first","affiliation":[{"name":"Department of Virology, The Stephan Angeloff Institute of Microbiology, Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5244-5429","authenticated-orcid":false,"given":"Marie-Line","family":"Joffret","sequence":"additional","affiliation":[{"name":"Department of Virology, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelina","family":"Stoyanova","sequence":"additional","affiliation":[{"name":"Department of Virology, The Stephan Angeloff Institute of Microbiology, Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patsy","family":"Polston","sequence":"additional","affiliation":[{"name":"Department of Virology, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emna","family":"Achouri","sequence":"additional","affiliation":[{"name":"Department of Virology, Institut Pasteur, Paris, France"},{"name":"Department of Computational Biology, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivanka","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Department of Virology, The Stephan Angeloff Institute of Microbiology, Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Delpeyroux","sequence":"additional","affiliation":[{"name":"Department of Virology, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8554-1655","authenticated-orcid":false,"given":"Angel S","family":"Galabov","sequence":"additional","affiliation":[{"name":"Department of Virology, The Stephan Angeloff Institute of Microbiology, Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,2,10]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1423-0127-16-103"},{"key":"e_1_3_4_3_2","article-title":"Human enterovirus 71 epidemics: What\u2019s next?","volume":"6","author":"Yip CCY","year":"2013","unstructured":"Yip CCY, Lau SKP, Woo PCYet\u00a0al. Human enterovirus 71 epidemics: What\u2019s next? Emerg Health Threats J 2013; 6. DOI: 10.3402\/ehtj.v6i0.19780.","journal-title":"Emerg Health Threats J"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-014-0087-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/1348-0421.12141"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-4-783"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2009.11.003"},{"key":"e_1_3_4_8_2","first-page":"47","volume-title":"New trends of microbiology (65th Anniversary of the Stephan Angeloff Institute of Microbiology)","author":"Galabov AS","year":"2012","unstructured":"Galabov AS, Nikolaeva-Glomb L, Nikolova Iet\u00a0al. Perspectives for effective chemotherapy of enterovirus infections. In: Najdenski H, Angelova M, Stoitsova S (eds) New trends of microbiology (65th Anniversary of the Stephan Angeloff Institute of Microbiology). Sofia: The Stephan Angeloff Institute of Microbiology, 2012, pp.47\u201381."},{"key":"e_1_3_4_9_2","first-page":"91","article-title":"Antiviral combination approach: A perspective to combat enterovirus infections","volume":"26","author":"Galabov AS","year":"2015","unstructured":"Galabov AS, Nikolova I, Vassileva-Pencheva Ret\u00a0al. Antiviral combination approach: A perspective to combat enterovirus infections. Prilozi\/Contributions 2015; 26: 91\u201399.","journal-title":"Prilozi\/Contributions"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.07.004"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","unstructured":"Stoyanova A Nikolova I P\u00fcrstinger Get\u00a0al. Anti-enteroviral triple combination of viral replication inhibitors: Activity on Coxsackievirus B1 induced neuroinfection in mice. 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