Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation

Detalhes bibliográficos
Autor(a) principal: Boff, Laurita
Data de Publicação: 2020
Outros Autores: Schreiber, André, Matos, Aline da Rocha, Del Sarto, Juliana, Brunotte, Linda, Munkert, Jennifer, Ottoni, Flaviano Melo, Ramos, Gabriela Silva, Kreis, Wolfang, Braga, Fernão Castro, Alves, Ricardo José, Pádua, Rodrigo Maia de, Simões, Cláudia Maria Oliveira, LUdwig, Stephan
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/45447
Resumo: Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany / Universidade Federal de Santa Catarina. Departamento de Ciências Faramacêuticas. Laboratório de Virologia Aplicada. Florianópolis, SC, Brasil.
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spelling Boff, LauritaSchreiber, AndréMatos, Aline da RochaDel Sarto, JulianaBrunotte, LindaMunkert, JenniferOttoni, Flaviano MeloRamos, Gabriela SilvaKreis, WolfangBraga, Fernão CastroAlves, Ricardo JoséPádua, Rodrigo Maia deSimões, Cláudia Maria OliveiraLUdwig, Stephan2020-12-28T15:21:04Z2020-12-28T15:21:04Z2020BOFF, Laurita et al. Semisynthetic Cardenolides Acting as Antiviral Inhibitors of Influenza A Virus Replication by Preventing Polymerase Complex Formation. Molecules, v. 25, p. 1-18, 2020.1420-3049https://www.arca.fiocruz.br/handle/icict/4544710.3390/molecules25204853engMDPICardenolides semisintéticosInibição da atividade de polimeraseMecanismo de açãoInibição da atividade de polimeraseSemisynthetic cardenolidesAnti-influenzaMechanism of actionPolymerase activity inhibitionSemisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleInstitute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany / Universidade Federal de Santa Catarina. Departamento de Ciências Faramacêuticas. Laboratório de Virologia Aplicada. Florianópolis, SC, Brasil.Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany.Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany / Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil.Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany.Pharmaceutical Biology, Department of Biology, Friedrich-Alexander-University, 91054 Erlangen-Nuremberg, Germany.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil.Pharmaceutical Biology, Department of Biology, Friedrich-Alexander-University, 91054 Erlangen-Nuremberg, Germany.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil.Universidade Federal de Santa Catarina. Departamento de Ciências Farmacêuticas. Laboratório de Virologia Aplicada. Florianópolis, SC, Brasil.Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany.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 (3β-((N-(2-hydroxyethyl)aminoacetyl)amino-3-deoxydigitoxigenin) and C11 (3β-(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 µM). Taken together, these promising results demonstrated that C10 and C11 can be considered as potential new anti-influenza drug candidates.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/45447/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAlineR_Matos_etal_IOC_2020.pdfAlineR_Matos_etal_IOC_2020.pdfapplication/pdf1379561https://www.arca.fiocruz.br/bitstream/icict/45447/2/AlineR_Matos_etal_IOC_2020.pdff7e46fc9b24856b4b7d8d20974072f06MD52TEXTAlineR_Matos_etal_IOC_2020.pdf.txtAlineR_Matos_etal_IOC_2020.pdf.txtExtracted texttext/plain75478https://www.arca.fiocruz.br/bitstream/icict/45447/3/AlineR_Matos_etal_IOC_2020.pdf.txte0325267cd9e568c04e9479060d67a6fMD53icict/454472020-12-29 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dc.title.pt_BR.fl_str_mv Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation
title Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation
spellingShingle Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation
Boff, Laurita
Cardenolides semisintéticos
Inibição da atividade de polimerase
Mecanismo de ação
Inibição da atividade de polimerase
Semisynthetic cardenolides
Anti-influenza
Mechanism of action
Polymerase activity inhibition
title_short Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation
title_full Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation
title_fullStr Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation
title_full_unstemmed Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation
title_sort Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation
author Boff, Laurita
author_facet Boff, Laurita
Schreiber, André
Matos, Aline da Rocha
Del Sarto, Juliana
Brunotte, Linda
Munkert, Jennifer
Ottoni, Flaviano Melo
Ramos, Gabriela Silva
Kreis, Wolfang
Braga, Fernão Castro
Alves, Ricardo José
Pádua, Rodrigo Maia de
Simões, Cláudia Maria Oliveira
LUdwig, Stephan
author_role author
author2 Schreiber, André
Matos, Aline da Rocha
Del Sarto, Juliana
Brunotte, Linda
Munkert, Jennifer
Ottoni, Flaviano Melo
Ramos, Gabriela Silva
Kreis, Wolfang
Braga, Fernão Castro
Alves, Ricardo José
Pádua, Rodrigo Maia de
Simões, Cláudia Maria Oliveira
LUdwig, Stephan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Boff, Laurita
Schreiber, André
Matos, Aline da Rocha
Del Sarto, Juliana
Brunotte, Linda
Munkert, Jennifer
Ottoni, Flaviano Melo
Ramos, Gabriela Silva
Kreis, Wolfang
Braga, Fernão Castro
Alves, Ricardo José
Pádua, Rodrigo Maia de
Simões, Cláudia Maria Oliveira
LUdwig, Stephan
dc.subject.other.pt_BR.fl_str_mv Cardenolides semisintéticos
Inibição da atividade de polimerase
Mecanismo de ação
Inibição da atividade de polimerase
topic Cardenolides semisintéticos
Inibição da atividade de polimerase
Mecanismo de ação
Inibição da atividade de polimerase
Semisynthetic cardenolides
Anti-influenza
Mechanism of action
Polymerase activity inhibition
dc.subject.en.pt_BR.fl_str_mv Semisynthetic cardenolides
Anti-influenza
Mechanism of action
Polymerase activity inhibition
description Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany / Universidade Federal de Santa Catarina. Departamento de Ciências Faramacêuticas. Laboratório de Virologia Aplicada. Florianópolis, SC, Brasil.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-12-28T15:21:04Z
dc.date.available.fl_str_mv 2020-12-28T15:21:04Z
dc.date.issued.fl_str_mv 2020
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv BOFF, Laurita et al. Semisynthetic Cardenolides Acting as Antiviral Inhibitors of Influenza A Virus Replication by Preventing Polymerase Complex Formation. Molecules, v. 25, p. 1-18, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/45447
dc.identifier.issn.pt_BR.fl_str_mv 1420-3049
dc.identifier.doi.none.fl_str_mv 10.3390/molecules25204853
identifier_str_mv BOFF, Laurita et al. Semisynthetic Cardenolides Acting as Antiviral Inhibitors of Influenza A Virus Replication by Preventing Polymerase Complex Formation. Molecules, v. 25, p. 1-18, 2020.
1420-3049
10.3390/molecules25204853
url https://www.arca.fiocruz.br/handle/icict/45447
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
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reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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