Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFU |
Texto Completo: | https://repositorio.ufu.br/handle/123456789/29449 http://doi.org/10.14393/ufu.di.2020.209 |
Resumo: | Chikungunya fever is a disease caused by the Chikungunya virus (CHIKV) that is transmitted by the bite of the female of Aedessp mosquito. The symptoms include fever, muscle aches, skin rash e and severe joint pains. The disease may develop into a chronic condition and joint pain that may last for months or years. Currently, there is no effective antiviral treatment against CHIKV infection, being necessary the development of novel therapies. Treatments based on natural compounds havebeen widely studied, as many drugs were produced by using natural molecules and their derivatives.Para-cymene (pCYM) is a naturally occurring aromatic organic compound that is a common ligand for ruthenium, forming the organometallic ruthenium and pCYM complex. Organometallic complexes have shown promising as a new generation of compounds that presented relevant biological properties, however, there is a lack of knowledge concerning the anti-CHIKV activity of these complexes. In this context, the present work evaluated the effects of the ruthenium and pCYM complex ([Ru2Cl4(η6-p-cymene)2]) (RcP) and its precursors on CHIKV infection in vitro. To this, BHK21 cells were infected with CHIKV-nanoluciferase (CHIKV-nanoluc), a viral construct with the reporter gene -nanoluc, at the presence or absence of the compounds for 16 hours, and citotoxicity (MTT) and infectivity (Luciferase) rates were accessed. The results demonstrated that RcPexhibited a strong therapeutic index judged by the selective index of 43.1(ratio of cytotoxicity to antiviral potency). Antiviral effects of RcPon different stages of the CHIKV replicative cycle were investigated and the results showed that it reduced 77% of virus entry to the host cells at non-toxic concentrations. Further assays demonstrated the virucidal activity of the compound that completely knocked down virus infectivity. Molecular docking calculations were performed in order to investigate possible interactions between pCYM and CHIKVglycoproteins and results suggested bindings between pCYM and a sitelocated behind the fusion loop between glycoproteins E3 and E2. Additionally, infrared spectroscopy spectral analysisindicated interactions of RcP with CHIKV glycoproteins.This data suggests that RcP may acts on CHIKV viral particles, disrupting virus entry to the host cells. Additional analyses are being performed to evaluate the mode of action of this complex. |
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Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitroRuthenium and para-cymene complex inhibits the Chikunguna virus in vitroVírus ChikungunyaAntiviralAreno complexoComplexo de rutênio e para-cimenoComplexos organometálicosChikungunya virusAntiviralArene complexRuthenium andpara-cymene complexOrganometallic complexesCNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS::VIROLOGIAChikungunya fever is a disease caused by the Chikungunya virus (CHIKV) that is transmitted by the bite of the female of Aedessp mosquito. The symptoms include fever, muscle aches, skin rash e and severe joint pains. The disease may develop into a chronic condition and joint pain that may last for months or years. Currently, there is no effective antiviral treatment against CHIKV infection, being necessary the development of novel therapies. Treatments based on natural compounds havebeen widely studied, as many drugs were produced by using natural molecules and their derivatives.Para-cymene (pCYM) is a naturally occurring aromatic organic compound that is a common ligand for ruthenium, forming the organometallic ruthenium and pCYM complex. Organometallic complexes have shown promising as a new generation of compounds that presented relevant biological properties, however, there is a lack of knowledge concerning the anti-CHIKV activity of these complexes. In this context, the present work evaluated the effects of the ruthenium and pCYM complex ([Ru2Cl4(η6-p-cymene)2]) (RcP) and its precursors on CHIKV infection in vitro. To this, BHK21 cells were infected with CHIKV-nanoluciferase (CHIKV-nanoluc), a viral construct with the reporter gene -nanoluc, at the presence or absence of the compounds for 16 hours, and citotoxicity (MTT) and infectivity (Luciferase) rates were accessed. The results demonstrated that RcPexhibited a strong therapeutic index judged by the selective index of 43.1(ratio of cytotoxicity to antiviral potency). Antiviral effects of RcPon different stages of the CHIKV replicative cycle were investigated and the results showed that it reduced 77% of virus entry to the host cells at non-toxic concentrations. Further assays demonstrated the virucidal activity of the compound that completely knocked down virus infectivity. Molecular docking calculations were performed in order to investigate possible interactions between pCYM and CHIKVglycoproteins and results suggested bindings between pCYM and a sitelocated behind the fusion loop between glycoproteins E3 and E2. Additionally, infrared spectroscopy spectral analysisindicated interactions of RcP with CHIKV glycoproteins.This data suggests that RcP may acts on CHIKV viral particles, disrupting virus entry to the host cells. Additional analyses are being performed to evaluate the mode of action of this complex.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorDissertação (Mestrado)A febre chikungunya é uma doença causada pelo vírus Chikungunya (CHIKV) transmitida pela picada da fêmea do mosquito Aedes sp. Os sintomas incluem febre, dores musculares, erupção cutânea e fortes dores nas articulações. A doença pode evoluir para uma condição crônica apresentando dores nas articulações por meses ou anos. Atualmente, não existe tratamento antiviral eficaz contra a infecção pelo CHIKV, sendo necessário o desenvolvimento de novas terapias. Tratamentos baseados em compostos naturais têm sido amplamente estudados, pois muitos medicamentos foram produzidos usando moléculas naturais e seus derivados. O para-cimeno (pCYM) é um composto orgânico aromático de ocorrência natural que é um ligante comum para o rutênio, formando o complexo organometálico de rutênio e pCYM. Os complexos organometálicos mostraram-se promissores como uma nova geração de compostos que apresentaram propriedades biológicas relevantes, no entanto, há um desconhecimento sobre a atividade anti-CHIKV desses complexos. Neste contexto, o presente trabalho avaliou os efeitos do complexo de rutênio e pCYM ([Ru2Cl4 (η6-p-cimeno) 2]) (RcP) e seus precursores na infecção por CHIKV in vitro. Para isso, as células BHK21 foram infectadas com CHIKV-nanoluciferase (CHIKV-nanoluc), uma construção viral com o gene repórter -nanoluc, na presença ou ausência dos compostos por 16 horas e taxas de citotoxicidade (MTT) e infectividade (luciferase) foram acessados. Os resultados demonstraram que oRcP exibiu um forte índice terapêutico avaliado pelo índice seletivo de 43,1 (razão entre citotoxicidade e potência antiviral). Os efeitos antivirais da RcP em diferentes estágios do ciclo replicativo do CHIKV foram investigados e os resultados mostraram que reduziu 77% da entrada do vírus nas células hospedeiras em concentrações não tóxicas. Ensaios adicionais demonstraram a atividade virucida do composto que inibiu completamente a infectividade do vírus. Análises de docking molecular foram realizados para investigar possíveis interações entre as glicoproteínas pCYM e CHIKV e os resultados sugeriram ligações entre pCYM e um local localizado atrás do loop de fusão entre as glicoproteínas E3 e E2. Além disso, a análise espectral por espectroscopia de infravermelho indicou interações de RcP com glicoproteínas CHIKV. Esses dados sugerem que a RcP pode atuar nas partículas virais do CHIKV, impedindo a entrada do vírus nas células hospedeiras. Análises adicionais estão sendo realizadas para avaliar o modo de ação desse complexo.Universidade Federal de UberlândiaBrasilPrograma de Pós-graduação em Imunologia e Parasitologia AplicadasPacca, Carolina Colombelli Mazarohttp://lattes.cnpq.br/2515945405129776Jardim, Ana Carolina Gomeshttp://lattes.cnpq.br/7960921685798643Teixeira, Samuel CotaOliva, Cíntia BitarOliveira, Débora Moraes Rossini2020-06-23T22:47:15Z2020-06-23T22:47:15Z2020-02-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfMORAES, Débora Oliveira Rossini. Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro. 2020. 85 f. Dissertação (Mestrado em Imunologia e Parasitologia Aplicadas). Universidade Federal de Uberlândia. Uberlândia, 2020. DOI http://doi.org/10.14393/ufu.di.2020.209.https://repositorio.ufu.br/handle/123456789/29449http://doi.org/10.14393/ufu.di.2020.209porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2020-06-24T06:17:07Zoai:repositorio.ufu.br:123456789/29449Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2020-06-24T06:17:07Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false |
dc.title.none.fl_str_mv |
Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro Ruthenium and para-cymene complex inhibits the Chikunguna virus in vitro |
title |
Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro |
spellingShingle |
Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro Oliveira, Débora Moraes Rossini Vírus Chikungunya Antiviral Areno complexo Complexo de rutênio e para-cimeno Complexos organometálicos Chikungunya virus Antiviral Arene complex Ruthenium andpara-cymene complex Organometallic complexes CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS::VIROLOGIA |
title_short |
Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro |
title_full |
Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro |
title_fullStr |
Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro |
title_full_unstemmed |
Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro |
title_sort |
Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro |
author |
Oliveira, Débora Moraes Rossini |
author_facet |
Oliveira, Débora Moraes Rossini |
author_role |
author |
dc.contributor.none.fl_str_mv |
Pacca, Carolina Colombelli Mazaro http://lattes.cnpq.br/2515945405129776 Jardim, Ana Carolina Gomes http://lattes.cnpq.br/7960921685798643 Teixeira, Samuel Cota Oliva, Cíntia Bitar |
dc.contributor.author.fl_str_mv |
Oliveira, Débora Moraes Rossini |
dc.subject.por.fl_str_mv |
Vírus Chikungunya Antiviral Areno complexo Complexo de rutênio e para-cimeno Complexos organometálicos Chikungunya virus Antiviral Arene complex Ruthenium andpara-cymene complex Organometallic complexes CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS::VIROLOGIA |
topic |
Vírus Chikungunya Antiviral Areno complexo Complexo de rutênio e para-cimeno Complexos organometálicos Chikungunya virus Antiviral Arene complex Ruthenium andpara-cymene complex Organometallic complexes CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS::VIROLOGIA |
description |
Chikungunya fever is a disease caused by the Chikungunya virus (CHIKV) that is transmitted by the bite of the female of Aedessp mosquito. The symptoms include fever, muscle aches, skin rash e and severe joint pains. The disease may develop into a chronic condition and joint pain that may last for months or years. Currently, there is no effective antiviral treatment against CHIKV infection, being necessary the development of novel therapies. Treatments based on natural compounds havebeen widely studied, as many drugs were produced by using natural molecules and their derivatives.Para-cymene (pCYM) is a naturally occurring aromatic organic compound that is a common ligand for ruthenium, forming the organometallic ruthenium and pCYM complex. Organometallic complexes have shown promising as a new generation of compounds that presented relevant biological properties, however, there is a lack of knowledge concerning the anti-CHIKV activity of these complexes. In this context, the present work evaluated the effects of the ruthenium and pCYM complex ([Ru2Cl4(η6-p-cymene)2]) (RcP) and its precursors on CHIKV infection in vitro. To this, BHK21 cells were infected with CHIKV-nanoluciferase (CHIKV-nanoluc), a viral construct with the reporter gene -nanoluc, at the presence or absence of the compounds for 16 hours, and citotoxicity (MTT) and infectivity (Luciferase) rates were accessed. The results demonstrated that RcPexhibited a strong therapeutic index judged by the selective index of 43.1(ratio of cytotoxicity to antiviral potency). Antiviral effects of RcPon different stages of the CHIKV replicative cycle were investigated and the results showed that it reduced 77% of virus entry to the host cells at non-toxic concentrations. Further assays demonstrated the virucidal activity of the compound that completely knocked down virus infectivity. Molecular docking calculations were performed in order to investigate possible interactions between pCYM and CHIKVglycoproteins and results suggested bindings between pCYM and a sitelocated behind the fusion loop between glycoproteins E3 and E2. Additionally, infrared spectroscopy spectral analysisindicated interactions of RcP with CHIKV glycoproteins.This data suggests that RcP may acts on CHIKV viral particles, disrupting virus entry to the host cells. Additional analyses are being performed to evaluate the mode of action of this complex. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-06-23T22:47:15Z 2020-06-23T22:47:15Z 2020-02-27 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
MORAES, Débora Oliveira Rossini. Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro. 2020. 85 f. Dissertação (Mestrado em Imunologia e Parasitologia Aplicadas). Universidade Federal de Uberlândia. Uberlândia, 2020. DOI http://doi.org/10.14393/ufu.di.2020.209. https://repositorio.ufu.br/handle/123456789/29449 http://doi.org/10.14393/ufu.di.2020.209 |
identifier_str_mv |
MORAES, Débora Oliveira Rossini. Complexo de rutênio e para-cimeno inibe o vírus Chikunguna in vitro. 2020. 85 f. Dissertação (Mestrado em Imunologia e Parasitologia Aplicadas). Universidade Federal de Uberlândia. Uberlândia, 2020. DOI http://doi.org/10.14393/ufu.di.2020.209. |
url |
https://repositorio.ufu.br/handle/123456789/29449 http://doi.org/10.14393/ufu.di.2020.209 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Uberlândia Brasil Programa de Pós-graduação em Imunologia e Parasitologia Aplicadas |
publisher.none.fl_str_mv |
Universidade Federal de Uberlândia Brasil Programa de Pós-graduação em Imunologia e Parasitologia Aplicadas |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFU instname:Universidade Federal de Uberlândia (UFU) instacron:UFU |
instname_str |
Universidade Federal de Uberlândia (UFU) |
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UFU |
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UFU |
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Repositório Institucional da UFU |
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Repositório Institucional da UFU |
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Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU) |
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diinf@dirbi.ufu.br |
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1805569732281106432 |