Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus

Detalhes bibliográficos
Autor(a) principal: Cassani, Natasha Marques
Data de Publicação: 2022
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFU
Texto Completo: https://repositorio.ufu.br/handle/123456789/35260
http://doi.org/10.14393/ufu.di.2022.327
Resumo: Zika virus (ZIKV) is the etiologic agent of Zika fever, a globally spreading mosquito-borne infection, previously associated with cases of microcephaly. Potential new outbreaks of ZIKV are priority problems for the governments since arboviruses are infections that are easily spread in tropical regions such as Brazil. According to the Ministry of Health, ZIKV represents a worldwide public health problem, resulting in social, economic, and public health system (SUS) significant impacts, since there is no effective antiviral treatment and licensed vaccines. In this context, natural compounds have several biological reported activities, such as antioxidant, antiparasitic, antibacterial, and antiviral, as well as toxins isolated from the venom of snakes have shown activity against several viruses. Here the anti-ZIKV activity of Bothropstoxins-I and II (BthTX-I and II) isolated from Bothrops jararacussu venom was investigated. Vero E6 cells were infected with ZIKVPE243 in the presence of compounds for 72 hours, when virus titers were quantified. The results demonstrated that BthTX-I and II presented strong dose-dependent inhibition, with a selective index of 149.1 and 1.44 x 105, respectively. These toxins mainly inhibited the early stages of the replicative cycle, such as during the entry of ZIKV into host cells, as shown by the potent virucidal effect, suggesting the action of these toxins on the virus particles. Moreover, BthTX-I and II presented significant activity towards the post‑entry stages of the ZIKV replicative cycle. Molecular docking analyses showed that BthTX-I and II potentially interact with ZIKV Envelope protein through hydrogen bonds and hydrophobic interactions. Our findings show that these toxins could be used as useful templates for the development of future antiviral candidate drugs against Zika fever.
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spelling Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírusAntiviral activity of bothrops jararacussu snake toxins in the replication cycle of the zika virusantiviralZika vírustoxinasantiviralToxinsCNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADACNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOSImunologiaAgentes antiviraisInfecção pelo Zika vírusVírus da ZikaToxinasZika virus (ZIKV) is the etiologic agent of Zika fever, a globally spreading mosquito-borne infection, previously associated with cases of microcephaly. Potential new outbreaks of ZIKV are priority problems for the governments since arboviruses are infections that are easily spread in tropical regions such as Brazil. According to the Ministry of Health, ZIKV represents a worldwide public health problem, resulting in social, economic, and public health system (SUS) significant impacts, since there is no effective antiviral treatment and licensed vaccines. In this context, natural compounds have several biological reported activities, such as antioxidant, antiparasitic, antibacterial, and antiviral, as well as toxins isolated from the venom of snakes have shown activity against several viruses. Here the anti-ZIKV activity of Bothropstoxins-I and II (BthTX-I and II) isolated from Bothrops jararacussu venom was investigated. Vero E6 cells were infected with ZIKVPE243 in the presence of compounds for 72 hours, when virus titers were quantified. The results demonstrated that BthTX-I and II presented strong dose-dependent inhibition, with a selective index of 149.1 and 1.44 x 105, respectively. These toxins mainly inhibited the early stages of the replicative cycle, such as during the entry of ZIKV into host cells, as shown by the potent virucidal effect, suggesting the action of these toxins on the virus particles. Moreover, BthTX-I and II presented significant activity towards the post‑entry stages of the ZIKV replicative cycle. Molecular docking analyses showed that BthTX-I and II potentially interact with ZIKV Envelope protein through hydrogen bonds and hydrophobic interactions. Our findings show that these toxins could be used as useful templates for the development of future antiviral candidate drugs against Zika fever.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoDissertação (Mestrado)Zika vírus (ZIKV) é o agente etiológico da febre Zika, uma infecção transmitida por mosquitos, de disseminação global, e previamente associada a casos de microcefalia. Potenciais novos surtos por ZIKV são problemas prioritários para os órgãos governamentais, visto que as arboviroses são infecções facilmente disseminadas em regiões tropicais como o Brasil. De acordo com o Ministério da Saúde, o ZIKV representa um problema de saúde pública mundial, resultando em impactos social, econômico e no sistema público de saúde (SUS) significativos, uma vez que não há tratamento antiviral eficaz ou vacinas licenciadas. Nesse contexto, compostos naturais apresentam diversas atividades biológicas reportadas, como antioxidante, antiparasitária, antibacteriana e antiviral, bem com toxinas isoladas de serpentes têm demonstrado atividade contra diversos vírus. Neste trabalho, a atividade anti-ZIKV das Bothropstoxinas-I e II (BthTX-I e II) isoladas do veneno de Bothrops jararacussu foi investigada contra o ZIKV in vitro. Células Vero E6 foram infectadas com ZIKVPE243 na presença dos compostos por 72 horas, quando os focos de infecção foram quantificados. Os resultados demonstraram que BthTX-I e II apresentaram potente inibição dose-dependente da infecção pelo ZIKV, com índice de seletividade de 149,1 e 1,44 x 105, respectivamente. Essas toxinas inibiram principalmente os estágios iniciais do ciclo replicativo do vírus, como a entrada do ZIKV nas células hospedeiras, demonstrado pelo potente efeito virucida, sugerindo a ação dessas toxinas sobre as partículas virais. Adicionalmente, BthTX-I e II apresentaram atividade significativa nos estágios tardios do ciclo replicativo do ZIKV. Análises de docking molecular mostraram que BthTX-I e II potencialmente interagem com a proteína do Envelope do ZIKV através de ligações de hidrogênio e interações hidrofóbicas. Nossos dados demostram que essas toxinas podem ser usadas como modelos úteis para o desenvolvimento de futuros antivirais contra a febre Zika.2024-07-13Universidade Federal de UberlândiaBrasilPrograma de Pós-graduação em Imunologia e Parasitologia AplicadasJardim, Ana Carolina Gomeshttp://lattes.cnpq.br/7960921685798643Corbi, Pedro Paulohttp://lattes.cnpq.br/5103173900175398Machado, Marcos Batistahttp://lattes.cnpq.br/9211305601802884Cassani, Natasha Marques2022-07-14T17:58:47Z2022-07-14T17:58:47Z2022-06-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfCASSANI, Natasha Marques. Atividade antiviral de toxinas de serpente Bothrops jararacussu no ciclo replicativo do Zika vírus in vitro. 2022. 62 f. Dissertação (Mestrado em Imunologia e Parasitologia Aplicadas) - Universidade Federal de Uberlândia, Uberlândia, 2022. DOI http://doi.org/10.14393/ufu.di.2022.327https://repositorio.ufu.br/handle/123456789/35260http://doi.org/10.14393/ufu.di.2022.327porhttp://creativecommons.org/licenses/by-nc-nd/3.0/us/info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2024-08-05T14:15:48Zoai:repositorio.ufu.br:123456789/35260Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2024-08-05T14:15:48Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false
dc.title.none.fl_str_mv Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus
Antiviral activity of bothrops jararacussu snake toxins in the replication cycle of the zika virus
title Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus
spellingShingle Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus
Cassani, Natasha Marques
antiviral
Zika vírus
toxinas
antiviral
Toxins
CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA
CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS
Imunologia
Agentes antivirais
Infecção pelo Zika vírus
Vírus da Zika
Toxinas
title_short Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus
title_full Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus
title_fullStr Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus
title_full_unstemmed Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus
title_sort Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus
author Cassani, Natasha Marques
author_facet Cassani, Natasha Marques
author_role author
dc.contributor.none.fl_str_mv Jardim, Ana Carolina Gomes
http://lattes.cnpq.br/7960921685798643
Corbi, Pedro Paulo
http://lattes.cnpq.br/5103173900175398
Machado, Marcos Batista
http://lattes.cnpq.br/9211305601802884
dc.contributor.author.fl_str_mv Cassani, Natasha Marques
dc.subject.por.fl_str_mv antiviral
Zika vírus
toxinas
antiviral
Toxins
CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA
CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS
Imunologia
Agentes antivirais
Infecção pelo Zika vírus
Vírus da Zika
Toxinas
topic antiviral
Zika vírus
toxinas
antiviral
Toxins
CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA
CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS
Imunologia
Agentes antivirais
Infecção pelo Zika vírus
Vírus da Zika
Toxinas
description Zika virus (ZIKV) is the etiologic agent of Zika fever, a globally spreading mosquito-borne infection, previously associated with cases of microcephaly. Potential new outbreaks of ZIKV are priority problems for the governments since arboviruses are infections that are easily spread in tropical regions such as Brazil. According to the Ministry of Health, ZIKV represents a worldwide public health problem, resulting in social, economic, and public health system (SUS) significant impacts, since there is no effective antiviral treatment and licensed vaccines. In this context, natural compounds have several biological reported activities, such as antioxidant, antiparasitic, antibacterial, and antiviral, as well as toxins isolated from the venom of snakes have shown activity against several viruses. Here the anti-ZIKV activity of Bothropstoxins-I and II (BthTX-I and II) isolated from Bothrops jararacussu venom was investigated. Vero E6 cells were infected with ZIKVPE243 in the presence of compounds for 72 hours, when virus titers were quantified. The results demonstrated that BthTX-I and II presented strong dose-dependent inhibition, with a selective index of 149.1 and 1.44 x 105, respectively. These toxins mainly inhibited the early stages of the replicative cycle, such as during the entry of ZIKV into host cells, as shown by the potent virucidal effect, suggesting the action of these toxins on the virus particles. Moreover, BthTX-I and II presented significant activity towards the post‑entry stages of the ZIKV replicative cycle. Molecular docking analyses showed that BthTX-I and II potentially interact with ZIKV Envelope protein through hydrogen bonds and hydrophobic interactions. Our findings show that these toxins could be used as useful templates for the development of future antiviral candidate drugs against Zika fever.
publishDate 2022
dc.date.none.fl_str_mv 2022-07-14T17:58:47Z
2022-07-14T17:58:47Z
2022-06-30
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 CASSANI, Natasha Marques. Atividade antiviral de toxinas de serpente Bothrops jararacussu no ciclo replicativo do Zika vírus in vitro. 2022. 62 f. Dissertação (Mestrado em Imunologia e Parasitologia Aplicadas) - Universidade Federal de Uberlândia, Uberlândia, 2022. DOI http://doi.org/10.14393/ufu.di.2022.327
https://repositorio.ufu.br/handle/123456789/35260
http://doi.org/10.14393/ufu.di.2022.327
identifier_str_mv CASSANI, Natasha Marques. Atividade antiviral de toxinas de serpente Bothrops jararacussu no ciclo replicativo do Zika vírus in vitro. 2022. 62 f. Dissertação (Mestrado em Imunologia e Parasitologia Aplicadas) - Universidade Federal de Uberlândia, Uberlândia, 2022. DOI http://doi.org/10.14393/ufu.di.2022.327
url https://repositorio.ufu.br/handle/123456789/35260
http://doi.org/10.14393/ufu.di.2022.327
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/us/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/us/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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)
instacron_str UFU
institution UFU
reponame_str Repositório Institucional da UFU
collection Repositório Institucional da UFU
repository.name.fl_str_mv Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)
repository.mail.fl_str_mv diinf@dirbi.ufu.br
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