qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties

Detalhes bibliográficos
Autor(a) principal: Silva, Marcos Túlio da
Data de Publicação: 2021
Outros Autores: Oliveira, Matheus Gabriel de, Paula, José Realino de, Silva, Vinicius Barreto da, Neves, Kidney de Oliveira Gomes, Machado, Marcos Batista, Nunomura, Rita de Cássia Saraiva
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Research, Society and Development
Texto Completo: https://rsdjournal.org/index.php/rsd/article/view/23220
Resumo: Objective: To quantify the quassinoids of P. sprucei, a medicinal plant that is native to the Amazon region, using qNMR and investigate the inhibitory potential of isobrucein B and neosergeolide on the 3CLpro and RdRp targets of SARS-CoV-2 through in silico approaches. Methods: the quantification was performed in a fraction (F2-F3) enriched with the quassinoids isobrucein B and neosergeolide using the PULCON method. In silico assays were performed using molecular docking to assess interactions and binding affinity between neosergeolide and isobrucein B ligands with SARS-CoV-2 3CLpro and RdRp targets, and online servers were used to estimate pharmacokinetic and toxicity. Results: It was possible to determine the quantity of the two quassinoids isobrucein B and neosergeolide in the F2-F3 fraction (769.6 mg), which were present in significant amounts in the PsMeOH extract (5.46%). The results of the docking analysis, based on the crystallized structures of RdRp and 3CLpro, indicated that isobrucein B and neosergeolide are potential inhibitors of the two proteins evaluated, as well as showing the importance of hydrogen bonding and pi (π) interactions for the active sites foreseen for each target. Conclusion: The results suggest that P. sprucei quassinoids may interact with 3CLpro and RdRp targets. In vitro and in vivo experiments are needed to confirm the results of molecular docking and investigate the risks of using P. sprucei as a medicinal plant against COVID-19.
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spelling qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological propertiesCuantificación por qNMR y análisis in silico de isobruceína B y neosergeolida de Picrolemma sprucei como inhibidores potenciales de la proteasa del SARS-CoV-2 (3CLpro) y la ARN polimerasa dependiente de ARN (RdRp) y propiedades farmacocinéticas y toxicológicasQuantificação por qRMN e análise in silico de isobruceína B e neosergeolida de Picrolemma sprucei como potenciais inibidores de protease SARS-CoV-2 (3CLpro) e RNA polimerase dependente de RNA (RdRp) e propriedades farmacocinéticas e toxicológicasQuassinoidsCaferanaMolecular DockingqNMRSARS-CoV-2.CuassinoidesCaferanaqRMNAcoplamiento molecularSARS-CoV-2.QuassinoidesCaferanaDocking molecularqRMNSARS-CoV-2.Objective: To quantify the quassinoids of P. sprucei, a medicinal plant that is native to the Amazon region, using qNMR and investigate the inhibitory potential of isobrucein B and neosergeolide on the 3CLpro and RdRp targets of SARS-CoV-2 through in silico approaches. Methods: the quantification was performed in a fraction (F2-F3) enriched with the quassinoids isobrucein B and neosergeolide using the PULCON method. In silico assays were performed using molecular docking to assess interactions and binding affinity between neosergeolide and isobrucein B ligands with SARS-CoV-2 3CLpro and RdRp targets, and online servers were used to estimate pharmacokinetic and toxicity. Results: It was possible to determine the quantity of the two quassinoids isobrucein B and neosergeolide in the F2-F3 fraction (769.6 mg), which were present in significant amounts in the PsMeOH extract (5.46%). The results of the docking analysis, based on the crystallized structures of RdRp and 3CLpro, indicated that isobrucein B and neosergeolide are potential inhibitors of the two proteins evaluated, as well as showing the importance of hydrogen bonding and pi (π) interactions for the active sites foreseen for each target. Conclusion: The results suggest that P. sprucei quassinoids may interact with 3CLpro and RdRp targets. In vitro and in vivo experiments are needed to confirm the results of molecular docking and investigate the risks of using P. sprucei as a medicinal plant against COVID-19.Objetivo: Cuantificar los cuassinoides de P. sprucei, una planta medicinal nativa de la región Amazónica, mediante qNMR e investigar a través de enfoques in silico, el potencial inhibitorio de isobruceína B y neosergeolida sobre objetivos 3CLpro y RdRp del SARS-CoV-2. Métodos: la cuantificación se realizó en una fracción (F2-F3) enriquecida con los cuassinoides isobruceína B y neosergeolida, utilizando qRMN por el método PULCON. Se realizaron ensayos in silico utilizando acoplamiento molecular para evaluar las interacciones y la afinidad de unión entre los ligantes de neosergeolida e isobruceína B con objetivos de SARS-CoV-2 3CLpro y RdRp, además se utilizaron servidores en línea para estimar la farmacocinética y la toxicidad. Resultados: se pudo determinar la cantidad en mg de los dos cuassinoides isobruceína B y neosergeolida en la fracción F2-F3 (769,6 mg), presentes en cantidades significativas en el extracto de PsMeOH (5,46%). Los resultados del análisis de acoplamiento molecular, basados en las estructuras cristalizadas de RdRp y 3CLpro, indicaron que isobruceína B y neosergeolida son inhibidores potenciales de las dos proteínas evaluadas, además de mostrar la importancia de los enlaces de hidrógeno y las interacciones pi (π) para los sitios activos previstos para cada objetivo. Conclusión: Los resultados sugieren que los cuassinoides de P. sprucei pueden interactuar con los objetivos 3CLpro y RdRp. Se necesitan más investigaciones y experimentos in vitro e in vivo para confirmar los resultados del acoplamiento molecular e investigar los riesgos de P. sprucei como planta medicinal contra COVID-19.Objetivo: Quantificar os quassinóides de P. sprucei, uma planta medicinal nativa da região amazônica, usando qRMN e investigar, o potencial inibitório da isobruceína B e neosergeolida nos alvos 3CLpro e RdRp da SARS-CoV-2 por meio de abordagens in silico. Métodos: a quantificação foi realizada em uma fração (F2-F3) enriquecida com os quassinóides isobruceína B e neosergeolida pelo método PULCON. Os ensaios in silico foram realizados por meio de docking molecular para avaliar a interações e afinidade de ligação entre os ligantes neosergeolida e isobruceína B com os alvos 3CLpro e RdRp da SARS-CoV-2 e servidores online foram utilizados para estimar os parâmetros farmacocinéticos e de toxicidade. Resultados: foi possível determinar a quantidade em mg dos dois quassinoides isobruceína B e neosergeolida na fração F2-F3 (769.6 mg), presentes em quantidades significativas no extrato PsMeOH (5,46%). Os resultados da análise de docking, com base nas estruturas cristalizadas de RdRp e 3CLpro, indicou isobruceína B e neosergeolida indicou que isobruceína B e neosergeolida são inibidores potenciais das duas proteínas avaliadas, bem como mostrou a importância da ligação de hidrogênio e interações pi (π) para os sítios ativos previstos para cada alvo. Conclusão: Os resultados sugerem que os quassinóides de P. sprucei  podem interagir com os alvos 3CLpro e RdRp. Experimentos in vitro e in vivo são necessários para confirmar os resultados de docking molecular e investigar os riscos de P. sprucei como planta medicinal contra a COVID-19.Research, Society and Development2021-12-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://rsdjournal.org/index.php/rsd/article/view/2322010.33448/rsd-v10i16.23220Research, Society and Development; Vol. 10 No. 16; e69101623220Research, Society and Development; Vol. 10 Núm. 16; e69101623220Research, Society and Development; v. 10 n. 16; e691016232202525-3409reponame:Research, Society and Developmentinstname:Universidade Federal de Itajubá (UNIFEI)instacron:UNIFEIenghttps://rsdjournal.org/index.php/rsd/article/view/23220/24782Copyright (c) 2021 Marcos Túlio da Silva; Matheus Gabriel de Oliveira; José Realino de Paula; Vinicius Barreto da Silva; Kidney de Oliveira Gomes Neves; Marcos Batista Machado; Rita de Cássia Saraiva Nunomurahttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessSilva, Marcos Túlio daOliveira, Matheus Gabriel de Paula, José Realino de Silva, Vinicius Barreto da Neves, Kidney de Oliveira Gomes Machado, Marcos Batista Nunomura, Rita de Cássia Saraiva 2021-12-20T11:03:07Zoai:ojs.pkp.sfu.ca:article/23220Revistahttps://rsdjournal.org/index.php/rsd/indexPUBhttps://rsdjournal.org/index.php/rsd/oairsd.articles@gmail.com2525-34092525-3409opendoar:2024-01-17T09:42:09.602152Research, Society and Development - Universidade Federal de Itajubá (UNIFEI)false
dc.title.none.fl_str_mv qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties
Cuantificación por qNMR y análisis in silico de isobruceína B y neosergeolida de Picrolemma sprucei como inhibidores potenciales de la proteasa del SARS-CoV-2 (3CLpro) y la ARN polimerasa dependiente de ARN (RdRp) y propiedades farmacocinéticas y toxicológicas
Quantificação por qRMN e análise in silico de isobruceína B e neosergeolida de Picrolemma sprucei como potenciais inibidores de protease SARS-CoV-2 (3CLpro) e RNA polimerase dependente de RNA (RdRp) e propriedades farmacocinéticas e toxicológicas
title qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties
spellingShingle qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties
Silva, Marcos Túlio da
Quassinoids
Caferana
Molecular Docking
qNMR
SARS-CoV-2.
Cuassinoides
Caferana
qRMN
Acoplamiento molecular
SARS-CoV-2.
Quassinoides
Caferana
Docking molecular
qRMN
SARS-CoV-2.
title_short qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties
title_full qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties
title_fullStr qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties
title_full_unstemmed qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties
title_sort qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties
author Silva, Marcos Túlio da
author_facet Silva, Marcos Túlio da
Oliveira, Matheus Gabriel de
Paula, José Realino de
Silva, Vinicius Barreto da
Neves, Kidney de Oliveira Gomes
Machado, Marcos Batista
Nunomura, Rita de Cássia Saraiva
author_role author
author2 Oliveira, Matheus Gabriel de
Paula, José Realino de
Silva, Vinicius Barreto da
Neves, Kidney de Oliveira Gomes
Machado, Marcos Batista
Nunomura, Rita de Cássia Saraiva
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Silva, Marcos Túlio da
Oliveira, Matheus Gabriel de
Paula, José Realino de
Silva, Vinicius Barreto da
Neves, Kidney de Oliveira Gomes
Machado, Marcos Batista
Nunomura, Rita de Cássia Saraiva
dc.subject.por.fl_str_mv Quassinoids
Caferana
Molecular Docking
qNMR
SARS-CoV-2.
Cuassinoides
Caferana
qRMN
Acoplamiento molecular
SARS-CoV-2.
Quassinoides
Caferana
Docking molecular
qRMN
SARS-CoV-2.
topic Quassinoids
Caferana
Molecular Docking
qNMR
SARS-CoV-2.
Cuassinoides
Caferana
qRMN
Acoplamiento molecular
SARS-CoV-2.
Quassinoides
Caferana
Docking molecular
qRMN
SARS-CoV-2.
description Objective: To quantify the quassinoids of P. sprucei, a medicinal plant that is native to the Amazon region, using qNMR and investigate the inhibitory potential of isobrucein B and neosergeolide on the 3CLpro and RdRp targets of SARS-CoV-2 through in silico approaches. Methods: the quantification was performed in a fraction (F2-F3) enriched with the quassinoids isobrucein B and neosergeolide using the PULCON method. In silico assays were performed using molecular docking to assess interactions and binding affinity between neosergeolide and isobrucein B ligands with SARS-CoV-2 3CLpro and RdRp targets, and online servers were used to estimate pharmacokinetic and toxicity. Results: It was possible to determine the quantity of the two quassinoids isobrucein B and neosergeolide in the F2-F3 fraction (769.6 mg), which were present in significant amounts in the PsMeOH extract (5.46%). The results of the docking analysis, based on the crystallized structures of RdRp and 3CLpro, indicated that isobrucein B and neosergeolide are potential inhibitors of the two proteins evaluated, as well as showing the importance of hydrogen bonding and pi (π) interactions for the active sites foreseen for each target. Conclusion: The results suggest that P. sprucei quassinoids may interact with 3CLpro and RdRp targets. In vitro and in vivo experiments are needed to confirm the results of molecular docking and investigate the risks of using P. sprucei as a medicinal plant against COVID-19.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-07
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://rsdjournal.org/index.php/rsd/article/view/23220
10.33448/rsd-v10i16.23220
url https://rsdjournal.org/index.php/rsd/article/view/23220
identifier_str_mv 10.33448/rsd-v10i16.23220
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://rsdjournal.org/index.php/rsd/article/view/23220/24782
dc.rights.driver.fl_str_mv https://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Research, Society and Development
publisher.none.fl_str_mv Research, Society and Development
dc.source.none.fl_str_mv Research, Society and Development; Vol. 10 No. 16; e69101623220
Research, Society and Development; Vol. 10 Núm. 16; e69101623220
Research, Society and Development; v. 10 n. 16; e69101623220
2525-3409
reponame:Research, Society and Development
instname:Universidade Federal de Itajubá (UNIFEI)
instacron:UNIFEI
instname_str Universidade Federal de Itajubá (UNIFEI)
instacron_str UNIFEI
institution UNIFEI
reponame_str Research, Society and Development
collection Research, Society and Development
repository.name.fl_str_mv Research, Society and Development - Universidade Federal de Itajubá (UNIFEI)
repository.mail.fl_str_mv rsd.articles@gmail.com
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