Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases

Chaves, Otávio Augusto; Lima, Carlyle Ribeiro; Fintelman-Rodrigues, Natalia; Sacramento, Carolina Q.; Freitas, Caroline S. de; Vazquez, Leonardo; Temerozo, Jairo R.; Rocha, Marco E.N.; Dias, Suelen S. G.; Carels, Nicolas; Bozza, Patrícia T.; Faria Neto, Hugo Caire Castro; Souza, Thiago Moreno L.

Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases

Detalhes bibliográficos
Autor(a) principal:	Chaves, Otávio Augusto
Data de Publicação:	2022
Outros Autores:	Lima, Carlyle Ribeiro, Fintelman-Rodrigues, Natalia, Sacramento, Carolina Q., Freitas, Caroline S. de, Vazquez, Leonardo, Temerozo, Jairo R., Rocha, Marco E.N., Dias, Suelen S. G., Carels, Nicolas, Bozza, Patrícia T., Faria Neto, Hugo Caire Castro, Souza, Thiago Moreno L.
Tipo de documento:	Artigo
Idioma:	eng
Título da fonte:	Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo:	https://www.arca.fiocruz.br/handle/icict/55227
Resumo:	Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.

Metadados do item

id	CRUZ_c4d20adc810ce7ad4d6361f97441551e
oai_identifier_str	oai:www.arca.fiocruz.br:icict/55227
network_acronym_str	CRUZ
network_name_str	Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str	2135
spelling	Chaves, Otávio AugustoLima, Carlyle RibeiroFintelman-Rodrigues, NataliaSacramento, Carolina Q.Freitas, Caroline S. deVazquez, LeonardoTemerozo, Jairo R.Rocha, Marco E.N.Dias, Suelen S. G.Carels, NicolasBozza, Patrícia T.Faria Neto, Hugo Caire CastroSouza, Thiago Moreno L.2022-10-21T11:28:14Z2022-10-21T11:28:14Z2022CHAVES, Otávio Augusto et al. Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases. International Journal of Biological Macromolecules, v. 222, Part A, p. 1015-1026, Dec. 2022.0141-8130https://www.arca.fiocruz.br/handle/icict/5522710.1016/j.ijbiomac.2022.09.204engScience DirectSARS-CoV-2COVID-19BiflavonóideSARS-CoV-2COVID-19BiflavonoidAgathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteasesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.Despite the fast development of vaccines, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still circulates through variants of concern (VoC) and escape the humoral immune response. SARS-CoV-2 has provoked over 200,000 deaths/months since its emergence and only a few antiviral drugs showed clinical benefit up to this moment. Thus, chemical structures endowed with anti-SARS-CoV-2 activity are important for continuous antiviral development and natural products represent a fruitful source of substances with biological activity. In the present study, agathisflavone (AGT), a biflavonoid from Anacardium occidentale was investigated as a candidate anti-SARS-CoV-2 compound. In silico and enzymatic analysis indicated that AGT may target mainly the viral main protease (Mpro) and not the papain-like protease (PLpro) in a non-competitive way. Cell-based assays in type II pneumocytes cell lineage (Calu-3) showed that SARS-CoV-2 is more susceptible to AGT than to apigenin (APG, monomer of AGT), in a dose-dependent manner, with an EC50 of 4.23 ± 0.21 μM and CC50 of 61.3 ± 0.1 μM and with a capacity to inhibit the level of pro-inflammatory mediator tumor necrosis factor-alpha (TNF-α). These results configure AGT as an interesting chemical scaffold for the development of novel semisynthetic antivirals against SARS-CoV-2.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/55227/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAugusto_Otávio_etal_IOC_COVID-19_2022.pdfAugusto_Otávio_etal_IOC_COVID-19_2022.pdfapplication/pdf2624066https://www.arca.fiocruz.br/bitstream/icict/55227/2/Augusto_Ot%c3%a1vio_etal_IOC_COVID-19_2022.pdf7b124ac8a8ac78f96ba022209305d829MD52icict/552272023-09-14 15:46:45.873oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-14T18:46:45Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv	Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases
title	Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases
spellingShingle	Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases Chaves, Otávio Augusto SARS-CoV-2 COVID-19 Biflavonóide SARS-CoV-2 COVID-19 Biflavonoid
title_short	Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases
title_full	Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases
title_fullStr	Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases
title_full_unstemmed	Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases
title_sort	Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases
author	Chaves, Otávio Augusto
author_facet	Chaves, Otávio Augusto Lima, Carlyle Ribeiro Fintelman-Rodrigues, Natalia Sacramento, Carolina Q. Freitas, Caroline S. de Vazquez, Leonardo Temerozo, Jairo R. Rocha, Marco E.N. Dias, Suelen S. G. Carels, Nicolas Bozza, Patrícia T. Faria Neto, Hugo Caire Castro Souza, Thiago Moreno L.
author_role	author
author2	Lima, Carlyle Ribeiro Fintelman-Rodrigues, Natalia Sacramento, Carolina Q. Freitas, Caroline S. de Vazquez, Leonardo Temerozo, Jairo R. Rocha, Marco E.N. Dias, Suelen S. G. Carels, Nicolas Bozza, Patrícia T. Faria Neto, Hugo Caire Castro Souza, Thiago Moreno L.
author2_role	author author author author author author author author author author author author
dc.contributor.author.fl_str_mv	Chaves, Otávio Augusto Lima, Carlyle Ribeiro Fintelman-Rodrigues, Natalia Sacramento, Carolina Q. Freitas, Caroline S. de Vazquez, Leonardo Temerozo, Jairo R. Rocha, Marco E.N. Dias, Suelen S. G. Carels, Nicolas Bozza, Patrícia T. Faria Neto, Hugo Caire Castro Souza, Thiago Moreno L.
dc.subject.other.en_US.fl_str_mv	SARS-CoV-2 COVID-19 Biflavonóide
topic	SARS-CoV-2 COVID-19 Biflavonóide SARS-CoV-2 COVID-19 Biflavonoid
dc.subject.en.en_US.fl_str_mv	SARS-CoV-2 COVID-19 Biflavonoid
description	Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.
publishDate	2022
dc.date.accessioned.fl_str_mv	2022-10-21T11:28:14Z
dc.date.available.fl_str_mv	2022-10-21T11:28:14Z
dc.date.issued.fl_str_mv	2022
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	CHAVES, Otávio Augusto et al. Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases. International Journal of Biological Macromolecules, v. 222, Part A, p. 1015-1026, Dec. 2022.
dc.identifier.uri.fl_str_mv	https://www.arca.fiocruz.br/handle/icict/55227
dc.identifier.issn.en_US.fl_str_mv	0141-8130
dc.identifier.doi.none.fl_str_mv	10.1016/j.ijbiomac.2022.09.204
identifier_str_mv	CHAVES, Otávio Augusto et al. Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases. International Journal of Biological Macromolecules, v. 222, Part A, p. 1015-1026, Dec. 2022. 0141-8130 10.1016/j.ijbiomac.2022.09.204
url	https://www.arca.fiocruz.br/handle/icict/55227
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	Science Direct
publisher.none.fl_str_mv	Science Direct
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
institution	FIOCRUZ
reponame_str	Repositório Institucional da FIOCRUZ (ARCA)
collection	Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv	https://www.arca.fiocruz.br/bitstream/icict/55227/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/55227/2/Augusto_Ot%c3%a1vio_etal_IOC_COVID-19_2022.pdf
bitstream.checksum.fl_str_mv	5a560609d32a3863062d77ff32785d58 7b124ac8a8ac78f96ba022209305d829
bitstream.checksumAlgorithm.fl_str_mv	MD5 MD5
repository.name.fl_str_mv	Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv	repositorio.arca@fiocruz.br
_version_	1813008898380005376

Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases

Registros relacionados