{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T18:08:05Z","timestamp":1784570885056,"version":"3.55.0"},"reference-count":74,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["CNPq grant number 200574\/2018-3"],"award-info":[{"award-number":["CNPq grant number 200574\/2018-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["grant number 305878\/2016-6"],"award-info":[{"award-number":["grant number 305878\/2016-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["grants SFB1009B02, LU477\/23-1, BR 5189\/1-1, KFO324"],"award-info":[{"award-number":["grants SFB1009B02, LU477\/23-1, BR 5189\/1-1, KFO324"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011264","name":"FP7 People: Marie-Curie Actions","doi-asserted-by":"publisher","award":["FP7 IRSES, grant 295251, WK"],"award-info":[{"award-number":["FP7 IRSES, grant 295251, WK"]}],"id":[{"id":"10.13039\/100011264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Influenza virus infections represent a major public health issue by causing annual epidemics and occasional pandemics that affect thousands of people worldwide. Vaccination is the main prophylaxis to prevent these epidemics\/pandemics, although the effectiveness of licensed vaccines is rather limited due to the constant mutations of influenza virus antigenic characteristics. The available anti-influenza drugs are still restricted and there is an increasing viral resistance to these compounds, thus highlighting the need for research and development of new antiviral drugs. In this work, two semisynthetic derivatives of digitoxigenin, namely C10 (3\u03b2-((N-(2-hydroxyethyl)aminoacetyl)amino-3-deoxydigitoxigenin) and C11 (3\u03b2-(hydroxyacetyl)amino-3-deoxydigitoxigenin), showed anti-influenza A virus activity by affecting the expression of viral proteins at the early and late stages of replication cycle, and altering the transcription and synthesis of new viral proteins, thereby inhibiting the formation of new virions. Such antiviral action occurred due to the interference in the assembly of viral polymerase, resulting in an impaired polymerase activity and, therefore, reducing viral replication. Confirming the in vitro results, a clinically relevant ex vivo model of influenza virus infection of human tumor-free lung tissues corroborated the potential of these compounds, especially C10, to completely abrogate influenza A virus replication at the highest concentration tested (2.0 \u00b5M). Taken together, these promising results demonstrated that C10 and C11 can be considered as potential new anti-influenza drug candidates.<\/jats:p>","DOI":"10.3390\/molecules25204853","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T02:01:42Z","timestamp":1603418502000},"page":"4853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Semisynthetic Cardenolides Acting as Antiviral Inhibitors of Influenza A Virus Replication by Preventing Polymerase Complex Formation"],"prefix":"10.3390","volume":"25","author":[{"given":"Laurita","family":"Boff","sequence":"first","affiliation":[{"name":"Institute of Virology (IVM), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms University (WWU), 48149 M\u00fcnster, Germany"},{"name":"Laboratory of Applied Virology, Department of Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Florian\u00f3polis, Santa Catarina 88040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Institute of Virology (IVM), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms University (WWU), 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"da Rocha Matos","sequence":"additional","affiliation":[{"name":"Institute of Virology (IVM), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms University (WWU), 48149 M\u00fcnster, Germany"},{"name":"Respiratory Viruses and Measles Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 22775-051, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Del Sarto","sequence":"additional","affiliation":[{"name":"Institute of Virology (IVM), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms University (WWU), 48149 M\u00fcnster, Germany"},{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Brunotte","sequence":"additional","affiliation":[{"name":"Institute of Virology (IVM), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms University (WWU), 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Munkert","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biology, Department of Biology, Friedrich-Alexander-University, 91054 Erlangen-Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-4336","authenticated-orcid":false,"given":"Flaviano","family":"Melo Ottoni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0085-9571","authenticated-orcid":false,"given":"Gabriela","family":"Silva Ramos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4239-4349","authenticated-orcid":false,"given":"Wolfgang","family":"Kreis","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biology, Department of Biology, Friedrich-Alexander-University, 91054 Erlangen-Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9468-376X","authenticated-orcid":false,"given":"Fern\u00e3o","family":"Castro Braga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Jos\u00e9 Alves","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Maia de P\u00e1dua","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, 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