The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/54666 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laboratório de Estrutura e Regulação de Proteínas. Rio de Janeiro, RJ, Brasil. |
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Miranda, Milene D.Chaves, Otávio AugustoRosa, Alice S.Azevedo, Alexandre R.Pinheiro, Luiz Carlos da SilvaSoares, Vinicius C.Dias, Suelen S. G.Abrantes, Juliana L.Bernardino, Alice Maria R.Paixão, Izabel C. P. PaixãoSouza, Thiago Moreno L.Fontes, Carlos Frederico L.2022-08-16T19:29:01Z2022-08-16T19:29:01Z2022MIRANDA, Milene D. et al. The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle.International Journal of Molecular Sciences, v. 23, 8135, p. 1 - 15, July 2022.1422--0067https://www.arca.fiocruz.br/handle/icict/5466610.3390/ ijms23158135engMDPIPirazolopiridinaAntiviralAncoragem molecularHSV-1ICP-27gDPyrazolopyridineAntiviralMolecular dockingHSV-1ICP-27gDThe Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laboratório de Estrutura e Regulação de Proteínas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Instituto Nacional para Ciência e Tecnologia sobre Inovação em Doenças de Populações Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral.Rio de Janeiro, RJ, Brasil.Centro Universitário UniLaSalle-RJ. Departamento de Engenharia de Produção. Niterói, RJ, BrasilUniversidade do Estado do Rio de Janeiro. Faculdade de Formação de Professores. Departamento .de Ciências. São Gonçalo, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Programa de Imunologia e Inflamação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Estrutura e Regulação de Proteínas, Instituto de Bioquímica Médica, Programa de Biologia Estrutural. Rio de Janeiro, RJ,Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de janiro, RJ, Brasil / Universidade Federal Fluminense. Programa em Neurologia e Neurociências e Programa de Biotecnologia Marinha. Programa de Pós-graduação em Ciências e Biotecnologia. Instituto de Biologia. Laboratório de Virologia Molecular. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Química, Departamento de Química Orgânica. Programa de Pós-graduação em Química. Niterói, RJ, Brasil.Universidade Federal Fluminense. Programa em Neurologia e Neurociências e Programa de Biotecnologia Marinha. Programa de Pós-graduação em Ciências e Biotecnologia. Instituto de Biologia. Laboratório de Virologia Molecular. Niterói, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Instituto Nacional para Ciência e Tecnologia sobre Inovação em Doenças de Populações Negligenciadas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laboratório de Estrutura e Regulação de Proteínas. Rio de Janeiro, RJ, Brasil.Herpes simplex virus type-1 (HSV-1) infection causes several disorders, and acyclovir is used as a reference compound. However, resistant strains are commonly observed. Herein, we investigate the effects of N-heterocyclic compounds (pyrazolopyridine derivatives), named ARA-04, ARA-05, and AM-57, on HSV-1 in vitro replication. We show that the 50% effective concentration (EC50) values of the compounds ARA-04, ARA-05, and AM-57 were 1.00 0.10, 1.00 0.05, and 0.70 0.10 M, respectively. These compounds presented high 50% cytotoxic concentration (CC50) values, which resulted in a selective index (SI) of 1000, 1000, and 857.1 for ARA-04, ARA-05, and AM-57, respectively. To gain insight into which step of the HSV-1 replication cycle these molecules would impair, we performed adsorption and penetration inhibition assays and time-of-addition experiments. Our results indicated that ARA-04 and ARA-05 affected viral adsorption, while AM-57 interfered with the virus replication during its - and -phases and decreased ICP27 content during initial and late events of HSV-1 replication. In addition, we also observed that AM-57 caused a strong decrease in viral gD content, which was reinforced by in silico calculations that suggested AM-57 interacts preferentially with the viral complex between a general transcription factor and virion protein (TFIIBc-VP16). In contrast, ARA-04 and ARA-05 interact preferentially in the proteins responsible for the viral adsorption process (nectin-1 and glycoprotein). Thus, our results suggest that the 1H-pyrazolo[3,4-b]pyridine derivatives inhibit the HSV-1 replicative cycle with a novel mechanism of action, and its scaffold can be used as a template for the synthesis of promising new molecules with antiviral effects, including to reinforce the presented data herein for a limited number of molecules.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALMileneMiranda_ThiagoSouza_IOC_etal_2022.pdfMileneMiranda_ThiagoSouza_IOC_etal_2022.pdfapplication/pdf2496440https://www.arca.fiocruz.br/bitstream/icict/54666/2/MileneMiranda_ThiagoSouza_IOC_etal_2022.pdf9d75c0a5ed7ac5d31383c80ae6d20ec6MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/54666/1/license.txt5a560609d32a3863062d77ff32785d58MD51icict/546662022-08-16 16:29:01.141oai:www.arca.fiocruz.br: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ório 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| dc.title.pt_BR.fl_str_mv |
The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle |
| title |
The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle |
| spellingShingle |
The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle Miranda, Milene D. Pirazolopiridina Antiviral Ancoragem molecular HSV-1 ICP-27 gD Pyrazolopyridine Antiviral Molecular docking HSV-1 ICP-27 gD |
| title_short |
The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle |
| title_full |
The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle |
| title_fullStr |
The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle |
| title_full_unstemmed |
The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle |
| title_sort |
The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle |
| author |
Miranda, Milene D. |
| author_facet |
Miranda, Milene D. Chaves, Otávio Augusto Rosa, Alice S. Azevedo, Alexandre R. Pinheiro, Luiz Carlos da Silva Soares, Vinicius C. Dias, Suelen S. G. Abrantes, Juliana L. Bernardino, Alice Maria R. Paixão, Izabel C. P. Paixão Souza, Thiago Moreno L. Fontes, Carlos Frederico L. |
| author_role |
author |
| author2 |
Chaves, Otávio Augusto Rosa, Alice S. Azevedo, Alexandre R. Pinheiro, Luiz Carlos da Silva Soares, Vinicius C. Dias, Suelen S. G. Abrantes, Juliana L. Bernardino, Alice Maria R. Paixão, Izabel C. P. Paixão Souza, Thiago Moreno L. Fontes, Carlos Frederico L. |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Miranda, Milene D. Chaves, Otávio Augusto Rosa, Alice S. Azevedo, Alexandre R. Pinheiro, Luiz Carlos da Silva Soares, Vinicius C. Dias, Suelen S. G. Abrantes, Juliana L. Bernardino, Alice Maria R. Paixão, Izabel C. P. Paixão Souza, Thiago Moreno L. Fontes, Carlos Frederico L. |
| dc.subject.other.pt_BR.fl_str_mv |
Pirazolopiridina Antiviral Ancoragem molecular HSV-1 ICP-27 gD |
| topic |
Pirazolopiridina Antiviral Ancoragem molecular HSV-1 ICP-27 gD Pyrazolopyridine Antiviral Molecular docking HSV-1 ICP-27 gD |
| dc.subject.en.pt_BR.fl_str_mv |
Pyrazolopyridine Antiviral Molecular docking HSV-1 ICP-27 gD |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laboratório de Estrutura e Regulação de Proteínas. Rio de Janeiro, RJ, Brasil. |
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2022 |
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2022-08-16T19:29:01Z |
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2022-08-16T19:29:01Z |
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2022 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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MIRANDA, Milene D. et al. The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle.International Journal of Molecular Sciences, v. 23, 8135, p. 1 - 15, July 2022. |
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https://www.arca.fiocruz.br/handle/icict/54666 |
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1422--0067 |
| dc.identifier.doi.none.fl_str_mv |
10.3390/ ijms23158135 |
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MIRANDA, Milene D. et al. The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle.International Journal of Molecular Sciences, v. 23, 8135, p. 1 - 15, July 2022. 1422--0067 10.3390/ ijms23158135 |
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