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

dc.creatorBoff, Laurita
dc.creatorSchreiber, André
dc.creatorMatos, Aline da Rocha
dc.creatorDel Sarto, Juliana
dc.creatorBrunotte, Linda
dc.creatorMunkert, Jennifer
dc.creatorOttoni, Flaviano Melo
dc.creatorRamos, Gabriela Silva
dc.creatorKreis, Wolfang
dc.creatorBraga, Fernão Castro
dc.creatorAlves, Ricardo José
dc.creatorPádua, Rodrigo Maia de
dc.creatorSimões, Cláudia Maria Oliveira
dc.creatorLUdwig, Stephan
dc.date2020-12-28T15:21:04Z
dc.date2020-12-28T15:21:04Z
dc.date2020
dc.date.accessioned2023-09-26T20:54:38Z
dc.date.available2023-09-26T20:54:38Z
dc.identifierBOFF, 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.identifier1420-3049
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/45447
dc.identifier10.3390/molecules25204853
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8866021
dc.descriptionInfluenza 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherMDPI
dc.rightsopen access
dc.subjectCardenolides semisintéticos
dc.subjectInibição da atividade de polimerase
dc.subjectMecanismo de ação
dc.subjectInibição da atividade de polimerase
dc.subjectSemisynthetic cardenolides
dc.subjectAnti-influenza
dc.subjectMechanism of action
dc.subjectPolymerase activity inhibition
dc.titleSemisynthetic Cardenolides acting as antiviral inhibitors of Influenza A virus replication by preventing Polymerase complex formation
dc.typeArticle


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