| Author | Boff, Laurita | |
| Author | Schreiber, André | |
| Author | Matos, Aline da Rocha | |
| Author | Del Sarto, Juliana | |
| Author | Brunotte, Linda | |
| Author | Munkert, Jennifer | |
| Author | Ottoni, Flaviano Melo | |
| Author | Ramos, Gabriela Silva | |
| Author | Kreis, Wolfang | |
| Author | Braga, Fernão Castro | |
| Author | Alves, Ricardo José | |
| Author | Pádua, Rodrigo Maia de | |
| Author | Simões, Cláudia Maria Oliveira | |
| Author | LUdwig, Stephan | |
| Access date | 2020-12-28T15:21:04Z | |
| Available date | 2020-12-28T15:21:04Z | |
| Document date | 2020 | |
| Citation | 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. | pt_BR |
| ISSN | 1420-3049 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/45447 | |
| Language | eng | pt_BR |
| Publisher | MDPI | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Cardenolides semisintéticos | pt_BR |
| Subject in Portuguese | Inibição da atividade de polimerase | pt_BR |
| Subject in Portuguese | Mecanismo de ação | pt_BR |
| Subject in Portuguese | Inibição da atividade de polimerase | pt_BR |
| Title | Semisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation | pt_BR |
| Type | Article | |
| DOI | 10.3390/molecules25204853 | |
| Abstract | 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. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany. | pt_BR |
| Affilliation | Pharmaceutical Biology, Department of Biology, Friedrich-Alexander-University, 91054 Erlangen-Nuremberg, Germany. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Pharmaceutical Biology, Department of Biology, Friedrich-Alexander-University, 91054 Erlangen-Nuremberg, Germany. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciências Farmacêuticas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Santa Catarina. Departamento de Ciências Farmacêuticas. Laboratório de Virologia Aplicada. Florianópolis, SC, Brasil. | pt_BR |
| Affilliation | Institute of Virology (IVM). Centre for Molecular Biology of Inflammation (ZMBE). Westfaelische Wilhelms University (WWU), 48149 Münster, Germany. | pt_BR |
| Subject | Semisynthetic cardenolides | pt_BR |
| Subject | Anti-influenza | pt_BR |
| Subject | Mechanism of action | pt_BR |
| Subject | Polymerase activity inhibition | pt_BR |
