Acridonas com potencial atividade antiviral na replicação do vírus Oropouche
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Data
2021-07-08
Autores
Avilla, Clarita Maria Secco
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Universidade Estadual Paulista (Unesp)
Resumo
O vírus Oropouche (OROV) é um arbovírus pertencente à família Peribunyaviridae, gênero Orthobunyavirus, foi isolado pela primeira vez em Trinidad Tobago em 1955. Em 1960 foi identificado pela primeira vez no Brasil, no estado do Pará e um ano depois foi registrada a primeira epidemia no mesmo estado. Depois disso, outras epidemias ocorreram, principalmente na região norte do Brasil. Todavia, relatos de casos e inquéritos sorológicos tem demostrado que o vírus esta se espalhado pelo Brasil e América Latina e é visto como candidato a uma próxima epidemia nas Américas. Os sintomas são semelhantes aos de outras arboviroses além de possíveis acometimentos no SNC. Atualmente, não existem vacinas ou antivirais contra o OROV. Desta forma, é de suma importância a busca por moléculas ativas no controle da infecção viral. Os derivados de acridonas já demonstraram atividade biológica no tratamento de doenças como câncer, Alzheimer, e em doenças infecciosas bacteriana, viral e por protozoários. Portanto, o objetivo deste estudo é analisar a ação de um painel de derivados de acridonas na inibição da replicação do OROV. Para tanto, um painel de onze acridonas (FAC2-FAC7, FAC15-FAC17 e FAC20-FAC22), foram testadas e quatro selecionadas (FAC16, FAC20, FAC21 e FAC22) para continuidade dos estudos. Inicialmente, realizou-se ensaio de viabilidade celular (MTT) (300-2,34µM), em linhagens celulares VERO, para definir a concentração viável dos compostos. Os resultados obtidos mostraram inibição total da replicação viral em células tratadas com as moléculas FAC20 e FAC22, não havendo formação de placas. Em relação a FAC21, a redução foi de 90%, enquanto a FAC16 reduziu aproximadamente 75% a formação de placas. Na avaliação da inibição da replicação viral pelo ensaio virucida a FAC20 inibiu completamente a formação de placas, já as FAC16 e FAC21 inibiram aproximadamente 85% e a FAC22 mostrou redução de 90% a replicação viral. Nos ensaios de imunofluorescência, os mesmos foram realizados com protocolo de tratamento, virucida e pré-tratamento, a inibição da replicação também foi observada nestes ensaios. Com o trabalho realizado, foi possível concluir que os derivados de acridona utilizados no presente estudo apresentam potencial na inibição da replicação do OROV in vitro.
The Oropouche virus (OROV) is an arbovirus that belongs to the Peribunyaviridae familiy, genus Orthobunyavirus, and was isolated for the first time in Trinidad Tobago in 1955. In 1960 it was identified for the first time in Brazil, in the state of Pará and a year later the first epidemic in the same state happened. After that, other epidemics occurred, mainly in the northern region of Brazil. However, case reports and serological surveys have shown that the virus is spreading in Brazil and Latin America and is seen as a candidate for an upcoming epidemics in the Americas. The symptoms are similar to those of other arboviruses in addition to possible CNS involvement. Currently, there are no vaccines or antivirals against OROV. Thus, the search for active molecules in the control of viral infection is extremely important. Acridone derivatives have already shown biological activity in the treatment of diseases such as cancer, Alzheimer's, and in infectious bacterial, viral and protozoan diseases. Therefore, the aim of this study was to analyze the action of an acridone derivative panel in inhibiting OROV replication. For this purpose, a panel of eleven acridones (FAC2-FAC7, FAC15-FAC17 and FAC20-FAC22), were tested and four selected (FAC16, FAC20, FAC21 and FAC22) to continue the studies. Initially, a cell viability test (MTT) (300-2.34µM) was carried out on VERO cell lines to define the viable concentration of the compounds. The results obtained showed total inhibition of viral replication in cells treated with the molecules FAC20 and FAC22, with no plaque formation. In relation to FAC21, the reduction was 90%, while FAC16 reduced approximately 75% of the formation of plaques. In assessing the inhibition of viral replication by the virucidal assay, FAC20 completely inhibited plaque formation, whereas FAC16 and FAC21 inhibited approximately 85% and FAC22 showed a 90% reduction in viral replication. In the immunofluorescence assays, which were performed with treatment protocol, virucide and pre-treatment, inhibition of replication was also observed in these assays. With the work done so far, it was possible to conclude that the acridone derivatives used in the present study have the potential to inhibit OROV in vitro replication.
The Oropouche virus (OROV) is an arbovirus that belongs to the Peribunyaviridae familiy, genus Orthobunyavirus, and was isolated for the first time in Trinidad Tobago in 1955. In 1960 it was identified for the first time in Brazil, in the state of Pará and a year later the first epidemic in the same state happened. After that, other epidemics occurred, mainly in the northern region of Brazil. However, case reports and serological surveys have shown that the virus is spreading in Brazil and Latin America and is seen as a candidate for an upcoming epidemics in the Americas. The symptoms are similar to those of other arboviruses in addition to possible CNS involvement. Currently, there are no vaccines or antivirals against OROV. Thus, the search for active molecules in the control of viral infection is extremely important. Acridone derivatives have already shown biological activity in the treatment of diseases such as cancer, Alzheimer's, and in infectious bacterial, viral and protozoan diseases. Therefore, the aim of this study was to analyze the action of an acridone derivative panel in inhibiting OROV replication. For this purpose, a panel of eleven acridones (FAC2-FAC7, FAC15-FAC17 and FAC20-FAC22), were tested and four selected (FAC16, FAC20, FAC21 and FAC22) to continue the studies. Initially, a cell viability test (MTT) (300-2.34µM) was carried out on VERO cell lines to define the viable concentration of the compounds. The results obtained showed total inhibition of viral replication in cells treated with the molecules FAC20 and FAC22, with no plaque formation. In relation to FAC21, the reduction was 90%, while FAC16 reduced approximately 75% of the formation of plaques. In assessing the inhibition of viral replication by the virucidal assay, FAC20 completely inhibited plaque formation, whereas FAC16 and FAC21 inhibited approximately 85% and FAC22 showed a 90% reduction in viral replication. In the immunofluorescence assays, which were performed with treatment protocol, virucide and pre-treatment, inhibition of replication was also observed in these assays. With the work done so far, it was possible to conclude that the acridone derivatives used in the present study have the potential to inhibit OROV in vitro replication.
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Palavras-chave
Arbovirus, Acridona, Orthobunyavirus, Terapêutica, Acridone, Therapeutics