Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.saa.2022.121751 http://hdl.handle.net/11449/241506 |
Resumo: | Human respiratory syncytial virus (hRSV) infections are one of the most causes of acute lower respiratory tract infections in children and elderly. The development of effective antiviral therapies or preventive vaccines against hRSV is not available yet. Thus, it is necessary to search for protein targets to combat this viral infection, as well as potential ways to block them. Non-Structural 1 (NS1) protein is an important factor for viral replication success since reduces the immune response by interacting with proteins in the type I interferon pathway. The influence of NS1 on the cell's immune response denotes the potential of its inhibition, being a possible target of treatment against hRSV infection. Here, it was studied the interaction of hRSV NS1 with natural flavonoids chrysin, morin, kaempferol, and myricetin and their mono-acetylated chrysin and penta-acetylated morin derivatives using spectroscopic techniques and computational simulations. The fluorescence data indicate that the binding affinities are on the order of 105 M−1, which are directly related to the partition coefficient of each flavonoid with Pearson's correlation coefficients of 0.76–0.80. The thermodynamic analysis suggests that hydrophobic interactions play a key role in the formation of the NS1/flavonoid complexes, with positive values of enthalpy and entropy changes. The computational approach proposes that flavonoids bind in a region of NS1 formed between the C-terminal α3-helix and the protein core, important for its biological function, and corroborate with experimental data revealing that hydrophobic contacts are important for the binding. Therefore, the present study provides relevant molecular details for the development of a possible new strategy to fight infections caused by hRSV. |
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Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulationsComputational simulationsFlavonoidhRSVNS1 proteinSpectroscopic techniquesHuman respiratory syncytial virus (hRSV) infections are one of the most causes of acute lower respiratory tract infections in children and elderly. The development of effective antiviral therapies or preventive vaccines against hRSV is not available yet. Thus, it is necessary to search for protein targets to combat this viral infection, as well as potential ways to block them. Non-Structural 1 (NS1) protein is an important factor for viral replication success since reduces the immune response by interacting with proteins in the type I interferon pathway. The influence of NS1 on the cell's immune response denotes the potential of its inhibition, being a possible target of treatment against hRSV infection. Here, it was studied the interaction of hRSV NS1 with natural flavonoids chrysin, morin, kaempferol, and myricetin and their mono-acetylated chrysin and penta-acetylated morin derivatives using spectroscopic techniques and computational simulations. The fluorescence data indicate that the binding affinities are on the order of 105 M−1, which are directly related to the partition coefficient of each flavonoid with Pearson's correlation coefficients of 0.76–0.80. The thermodynamic analysis suggests that hydrophobic interactions play a key role in the formation of the NS1/flavonoid complexes, with positive values of enthalpy and entropy changes. The computational approach proposes that flavonoids bind in a region of NS1 formed between the C-terminal α3-helix and the protein core, important for its biological function, and corroborate with experimental data revealing that hydrophobic contacts are important for the binding. Therefore, the present study provides relevant molecular details for the development of a possible new strategy to fight infections caused by hRSV.Department of Physics Institute of Biosciences Letters and Exact Sciences (IBILCE) São Paulo State University “Júlio de Mesquita Filho” (UNESP), SPMultiuser Center for Biomolecular Innovation (CMIB) Department of Physics Institute of Biosciences Letters and Exact Sciences (IBILCE) São Paulo State University “Júlio de Mesquita Filho” (UNESP), SPDepartment of Chemistry and Environmental Sciences Institute of Biosciences Letters and Exact Sciences (IBILCE) São Paulo State University “Júlio de Mesquita Filho” (UNESP), SPInstitute of Medical Biochemistry Leopoldo de Meis and National Center for Structural Biology and Bioimaging Federal University of Rio de Janeiro, RJDepartment of Physics Institute of Biosciences Letters and Exact Sciences (IBILCE) São Paulo State University “Júlio de Mesquita Filho” (UNESP), SPMultiuser Center for Biomolecular Innovation (CMIB) Department of Physics Institute of Biosciences Letters and Exact Sciences (IBILCE) São Paulo State University “Júlio de Mesquita Filho” (UNESP), SPDepartment of Chemistry and Environmental Sciences Institute of Biosciences Letters and Exact Sciences (IBILCE) São Paulo State University “Júlio de Mesquita Filho” (UNESP), SPUniversidade Estadual Paulista (UNESP)Federal University of Rio de JaneiroOttenio de Lourenço, Isabella [UNESP]Toscano Pedroso Quintino, Evelyn [UNESP]Henrique Pereira, Matheus [UNESP]Sprengel Lima, Caroline [UNESP]Campos Araújo, Gabriela [UNESP]Octávio Regasini, Luis [UNESP]Alves de Melo, Fernando [UNESP]Pereira de Souza, Fátima [UNESP]Andres Fossey, Marcelo [UNESP]Putinhon Caruso, Ícaro [UNESP]2023-03-01T21:06:59Z2023-03-01T21:06:59Z2022-12-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.saa.2022.121751Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, v. 283.1386-1425http://hdl.handle.net/11449/24150610.1016/j.saa.2022.1217512-s2.0-85135882461Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengSpectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopyinfo:eu-repo/semantics/openAccess2023-03-01T21:07:00Zoai:repositorio.unesp.br:11449/241506Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-03-01T21:07Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations |
title |
Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations |
spellingShingle |
Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations Ottenio de Lourenço, Isabella [UNESP] Computational simulations Flavonoid hRSV NS1 protein Spectroscopic techniques |
title_short |
Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations |
title_full |
Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations |
title_fullStr |
Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations |
title_full_unstemmed |
Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations |
title_sort |
Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations |
author |
Ottenio de Lourenço, Isabella [UNESP] |
author_facet |
Ottenio de Lourenço, Isabella [UNESP] Toscano Pedroso Quintino, Evelyn [UNESP] Henrique Pereira, Matheus [UNESP] Sprengel Lima, Caroline [UNESP] Campos Araújo, Gabriela [UNESP] Octávio Regasini, Luis [UNESP] Alves de Melo, Fernando [UNESP] Pereira de Souza, Fátima [UNESP] Andres Fossey, Marcelo [UNESP] Putinhon Caruso, Ícaro [UNESP] |
author_role |
author |
author2 |
Toscano Pedroso Quintino, Evelyn [UNESP] Henrique Pereira, Matheus [UNESP] Sprengel Lima, Caroline [UNESP] Campos Araújo, Gabriela [UNESP] Octávio Regasini, Luis [UNESP] Alves de Melo, Fernando [UNESP] Pereira de Souza, Fátima [UNESP] Andres Fossey, Marcelo [UNESP] Putinhon Caruso, Ícaro [UNESP] |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Federal University of Rio de Janeiro |
dc.contributor.author.fl_str_mv |
Ottenio de Lourenço, Isabella [UNESP] Toscano Pedroso Quintino, Evelyn [UNESP] Henrique Pereira, Matheus [UNESP] Sprengel Lima, Caroline [UNESP] Campos Araújo, Gabriela [UNESP] Octávio Regasini, Luis [UNESP] Alves de Melo, Fernando [UNESP] Pereira de Souza, Fátima [UNESP] Andres Fossey, Marcelo [UNESP] Putinhon Caruso, Ícaro [UNESP] |
dc.subject.por.fl_str_mv |
Computational simulations Flavonoid hRSV NS1 protein Spectroscopic techniques |
topic |
Computational simulations Flavonoid hRSV NS1 protein Spectroscopic techniques |
description |
Human respiratory syncytial virus (hRSV) infections are one of the most causes of acute lower respiratory tract infections in children and elderly. The development of effective antiviral therapies or preventive vaccines against hRSV is not available yet. Thus, it is necessary to search for protein targets to combat this viral infection, as well as potential ways to block them. Non-Structural 1 (NS1) protein is an important factor for viral replication success since reduces the immune response by interacting with proteins in the type I interferon pathway. The influence of NS1 on the cell's immune response denotes the potential of its inhibition, being a possible target of treatment against hRSV infection. Here, it was studied the interaction of hRSV NS1 with natural flavonoids chrysin, morin, kaempferol, and myricetin and their mono-acetylated chrysin and penta-acetylated morin derivatives using spectroscopic techniques and computational simulations. The fluorescence data indicate that the binding affinities are on the order of 105 M−1, which are directly related to the partition coefficient of each flavonoid with Pearson's correlation coefficients of 0.76–0.80. The thermodynamic analysis suggests that hydrophobic interactions play a key role in the formation of the NS1/flavonoid complexes, with positive values of enthalpy and entropy changes. The computational approach proposes that flavonoids bind in a region of NS1 formed between the C-terminal α3-helix and the protein core, important for its biological function, and corroborate with experimental data revealing that hydrophobic contacts are important for the binding. Therefore, the present study provides relevant molecular details for the development of a possible new strategy to fight infections caused by hRSV. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-15 2023-03-01T21:06:59Z 2023-03-01T21:06:59Z |
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.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.saa.2022.121751 Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, v. 283. 1386-1425 http://hdl.handle.net/11449/241506 10.1016/j.saa.2022.121751 2-s2.0-85135882461 |
url |
http://dx.doi.org/10.1016/j.saa.2022.121751 http://hdl.handle.net/11449/241506 |
identifier_str_mv |
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, v. 283. 1386-1425 10.1016/j.saa.2022.121751 2-s2.0-85135882461 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799964505888784384 |