Navegando por Autor "Ferraz, Ariane Coelho"

Agora exibindo 1 - 15 de 15

Antioxidant and antiviral activity of fullerol against Zika virus.
(2021) Pereira, Samille Henriques; Almeida, Letícia Trindade; Ferraz, Ariane Coelho; Ladeira, Marina de Souza; Ladeira, Luiz Orlando; Magalhães, Cíntia Lopes de Brito; Silva, Breno de Mello
Neglected for years, Zika virus (ZIKV) has become one of the most relevant arboviruses in current public health. The recent Zika fever epidemic in the Americas generated a worldwide alert due to the association with diseases such as Guillain-Barr ́e syndrome and congenital syndromes. Among the pathogenesis of ZIKV, recent studies suggest that oxidative stress plays an important role during infection and that compounds capable of modulating oxidative stress are promising as therapeutics. Furthermore, so far there are no specific and efficient antiviral drug or vaccine available against ZIKV. Thus, fullerol was evaluated in the context of infection by ZIKV, since it is a carbon nanomaterial known for its potent antioxidant action. In this study, fullerol did not alter cell viability at the concentrations tested, proving to be inert, beyond to presenting high antioxidant power at low concentra- tions. ZIKV infection of human glioblastoma increased the production of reactive oxygen species by 60% and modulated the Nrf-2 pathway activity negatively. After treatment with fullerol, both conditions were restored to baseline levels. Additionally, fullerol was able to reduce viral production by up to 90%. Therefore, our results suggest that fullerol as a promising candidate in the control of ZIKV infections, presenting both antioxidant and antiviral action.
Antiviral activity of silymarin against Mayaro virus and protective effect in virus-induced oxidative stress.
(2018) Camini, Fernanda Caetano; Silva, Tales Fernando da; Caetano, Camila Carla da Silva; Almeida, Letícia Trindade; Ferraz, Ariane Coelho; Vitoreti, Verônica Maria Alves; Silva, Breno de Mello; Silva, Silvana de Queiroz; Magalhães, José Carlos de; Magalhães, Cíntia Lopes de Brito
Mayaro virus (MAYV) is a neglected arbovirus belonging to the family Togaviridae. Its infection leads to Mayaro fever, with clinical manifestations such as fever, myalgia, headache, rash, arthralgia, vomiting, and diarrhea. The most prominent complaint from infected person is the long-lasting arthritis/arthralgia. The treatment for Mayaro fever is mainly symptom-based and there are no vaccines or antiviral drugs currently available, thus, natural products with anti-MAYV activity may provide a potential alternative. Recent evidences suggest that oxidative stress plays an important role in MAYV infection and compounds capable of modulating oxidative stress could represent a novel therapeutic approach in modulating MAYV-associated oxidative cellular damage. Silymarin is a complex extracted of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. Its antioxidant and antiviral effects, including its antiviral activity against the Chikungunya virus (CHIKV), prompted us to think whether silymarin could also reduce the replication of the MAYV and restore the pro-oxidant/antioxidant balance in the context of MAYV infection, leading to reduced cellular oxidative stress. We assessed the antiviral activity and protective effect of silymarin against oxidative stress in MAYV-infected HepG2 cells. Cytopathic effect inhibition, viral replication, and plaque reduction assays were used to determine the anti-MAYV activity of silymarin. Additionally, we determined whether silymarin could reduce MAYV-induced oxidative cell damage. Briefly, silymarin exhibited potent antiviral activity against MAYV and reduced MAYV-induced ROS formation and levels of malondialdehyde (MDA) and carbonyl protein, which are biomarkers of oxidative stress. In conclusion, the ability of silymarin to inhibit MAYV replication and attenuate MAYV-induce oxidative stress warrants further investigation of this compound as a novel therapeutic approach to Mayaro fever disease.
Antiviral effect of silymarin against Zika virus in vitro.
(2020) Silva, Tales Fernando da; Ferraz, Ariane Coelho; Almeida, Letícia Trindade; Caetano, Camila Carla da Silva; Camini, Fernanda Caetano; Lima, Rafaela Lameira Souza; Andrade, Ana Cláudia dos Santos Pereira; Oliveira, Danilo Bretas de; Rocha, Kamila Lorene Soares; Silva, Breno de Mello; Magalhães, José Carlos de; Magalhães, Cíntia Lopes de Brito
Zika virus (ZIKV) epidemic and its association with severe neurological syndromes have raised worldwide concern. Despite the great clinical relevance of this infection, no vaccine or specific treatment is available and the search for antiviral compounds against ZIKV is extremely necessary. Several natural compounds, such as silymarin, exhibit antioxidant, hepatoprotective, and antiviral properties; however, the antiviral potential of this compound remains partially investigated. Therefore, the objective of this study was to evaluate in vitro the antiviral activity of silymarin against ZIKV infection. Global antiviral activity, dose-dependent, plaque reduction, and time-of-drug-addition assays were used to determine the anti-ZIKV activity of silymarin. Additionally, to start characterizing the mechanisms of action we determined whether silymarin could have a virucidal effect and inhibit viral adsorption and penetration stages. Regarding its global antiviral activity, silymarin showed significant inhibition of ZIKV infection, protecting cells infected with EC50 equal to 34.17μg/mL, with a selectivity index greater than 17 and 4x greater than that of the positive control (ribavirin). Its greatest efficiency was achieved at 125μg/mL, whose cell viability did not differ from the control without infection and treatment. Furthermore, treatment with silymarin reduced viral load by up to two logs (> 90%) concerning viral control, when evaluating virucidal activity and the precocious times of infection. Thus, our results set to show the promising anti-ZIKV activity of silymarin, which does not seem to have a single inhibition mechanism, acting at different times of infection, and still has the advantage of silymarin be a phytotherapy already available on the market.
Avaliação da atividade hepatoprotetora, antioxidante, anti-inflamatória e antiviral da silimarina em camundongos BALB/c infectados com o vírus Mayaro.
(2022) Ferraz, Ariane Coelho; Magalhães, Cíntia Lopes de Brito; Magalhães, José Carlos de; Magalhães, Cíntia Lopes de Brito; Magalhães, José Carlos de; Souza, Daniele da Glória de; Costa, Vivian Vasconcelos; Costa, Daniela Caldeira; Brandão, Geraldo Célio
Embora pouco conhecido pela população, o vírus Mayaro (MAYV), agente etiológico da Febre Mayaro, é responsável por causar doença febril aguda inespecífica, na qual a maioria dos pacientes desenvolve artrite/artralgia incapacitante e persistente. A Febre Mayaro é uma doença negligenciada e subnotificada, sem tratamento ou vacina, que vem ganhando atenção nos últimos anos após a observação laboratorial da competência do vetor urbano Aedes aegypti transmitir o vírus. Além disso, com a crescente modificação humana do ecossistema, os casos de Febre Mayaro estão sendo cada vez mais relatados fora de áreas florestais endêmicas, sendo um alerta sobre a possibilidade de estabelecimento de uma epidemia em um futuro próximo. Assim, para mitigar a falta de informações sobre os aspectos patológicos decorrentes da infecção pelo MAYV, descrevemos anteriormente o envolvimento do estresse oxidativo em cultura de células hepáticas infectadas e também em um modelo animal susceptível à infecção. Esses trabalhos ascenderam questões sobre uma possível abordagem terapêutica utilizando compostos antioxidantes na tentativa de modular o dano celular oxidativo desencadeado pelo MAYV. Então, mostramos que a silimarina, um complexo de antioxidantes obtido da erva Silybum marianum, atenuou o estresse oxidativo induzido pelo MAYV, bem como foi capaz de exercer atividade antiviral em cultura de células, uma vez que reduziu significativamente a multiplicação viral. Dessa forma, esses resultados in vitro nos levaram a determinar se a silimarina poderia reduzir o dano hepático e a inflamação, além do estresse oxidativo e da multiplicação do MAYV após a infecção em um modelo animal imunocompetente. Assim sendo, no presente trabalho, demostramos que camundongos BALB/c (3 semanas) infectados via subcutânea com o MAYV são susceptíveis à infecção, sem mortalidade, mas com menor ganho de peso, hepatomegalia, esplenomegalia, anemia, trombocitopenia, leucopenia e aumento dos níveis séricos das transaminases hepáticas. Ainda, no fígado desses animais observamos aumento de citocinas pró-inflamatórias, infiltrado inflamatório, aumento dos biomarcadores de estresse oxidativo e redução do sistema de defesa antioxidante. No entanto, no grupo de animais infectados e tratados com silimarina (100mg/kg/dia via gavagem) durante 5 dias, todos esses parâmetros foram revertidos ou significativamente melhorados, e a detecção de carga viral no fígado, baço, cérebro, músculo quadríceps e pata foi significativamente reduzida. Portanto, este trabalho reforça os potentes efeitos hepatoprotetor, antioxidante, antiinflamatório e antiviral da silimarina contra a infecção por MAYV, demonstrando seu potencial terapêutico contra a Febre Mayaro.
Detection of the antiviral activity of epicatechin isolated from Salacia crassifolia (Celastraceae) against Mayaro virus based on protein C homology modelling and virtual screening.
(2018) Ferreira, Priscila Gonçalves; Ferraz, Ariane Coelho; Figueiredo, Jenyfer Emanuelle; Lima, Caroline Ferrante; Rodrigues, Vanessa Gregório; Taranto, Alex Gutterres; Ferreira, Jaqueline Maria Siqueira; Brandão, Geraldo Célio; Vieira Filho, Sidney Augusto; Duarte, Lucienir Pains; Magalhães, Cíntia Lopes de Brito; Magalhães, José Carlos de
Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC50) of 0.247 μmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC50) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.
Evaluation of the activity of Tontelea micrantha extracts against Bacteria, Candida and Mayaro virus.
(2018) Nizer, Waleska Stephanie da Cruz; Ferraz, Ariane Coelho; Lima, William Gustavo de; Moraes, Thaís de Fátima Silva; Ferreira, Fernanda Lopes; Ferreira, Jaqueline Maria Siqueira; Magalhães, Cíntia Lopes de Brito; Duarte, Lucienir Pains; Vieira Filho, Sidney Augusto; Magalhães, José Carlos de
Objectives: This work aimed to evaluate the antibacterial, antifungal, and anti-Mayaro virus(MAYV) activity of leaf and branch extracts from Tontelea micrantha. Materials and Methods: T. micrantha extracts were prepared through the partition of the leaf and branch samples in different solvents. Then, the antibacterial and antifungal activity was assessed against bacterial pathogens and Candida sp. by the determination of the minimum inhibitory concentration (MIC) by the broth microdilution method. The activity against anti-MAYV was evaluated through the quantification of the extract concentration that promoted the protection of 50% of the cells after the viral infection. Results: The extracts of T. micrantha were inactive (MIC >500 µg/mL) against Gram-positive, Gram-negative and Candida species at the highest concentration tested (500 µg/mL). Anti-MAYV activity was also not detected, with SI <10, ranging from 1.2 to 3.6. Conclusion: Although it is used in traditional medicine, Leaf and branch extracts from T. micrantha did not present antimicrobial activity, which could be caused by the antagonistic effect of the compounds present in the extract.
Hepatoprotective, antioxidant, anti-inflammatory, and antiviral activities of silymarin against mayaro virus infection.
(2021) Ferraz, Ariane Coelho; Almeida, Letícia Trindade; Caetano, Camila Carla da Silva; Menegatto, Marília Bueno da Silva; Lima, Rafaela Lameira Souza; Senna, João Pinto Nelson de; Cardoso, Jamille Mirelle de Oliveira; Perucci, Luiza Oliveira; Silva, André Talvani Pedrosa da; Lima, Wanderson Geraldo de; Silva, Breno de Mello; Reis, Alexandre Barbosa; Magalhães, José Carlos de; Magalhães, Cíntia Lopes de Brito
Infection caused by Mayaro virus (MAYV) is responsible for causing acute nonspecific fever, in which the ma- jority of patients develop incapacitating and persistent arthritis/arthralgia. Mayaro fever is a neglected and underreported disease without treatment or vaccine, which has gained attention in recent years after the competence of Aedes aegypti to transmit MAYV was observed in the laboratory, coupled with the fact that cases are being increasingly reported outside of endemic forest areas, calling attention to the potential of an urban cycle arising in the near future. Thus, to mitigate the lack of information about the pathological aspects of MAYV, we previously described the involvement of oxidative stress in MAYV infection in cultured cells and in a non- lethal mouse model. Additionally, we showed that silymarin, a natural compound, attenuated MAYV-induced oxidative stress and inhibited MAYV replication in cells. The antioxidant and anti-MAYV effects prompted us to determine whether silymarin could also reduce oxidative stress and MAYV replication after infection in an immunocompetent animal model. We show that infected mice exhibited reduced weight gain, hepatomegaly, splenomegaly, anaemia, thrombocytopenia, leukopenia, increased liver transaminases, increased pro- inflammatory cytokines and liver inflammation, increased oxidative damage biomarkers, and reduced antioxi- dant enzyme activity. However, in animals infected and treated with silymarin, all these parameters were reversed or significantly improved, and the detection of viral load in the liver, spleen, brain, thigh muscle, and footpad was significantly reduced. This work reinforces the potent hepatoprotective, antioxidant, anti- inflammatory, and antiviral effects of silymarin against MAYV infection, demonstrating its potential against Mayaro fever disease.
Lack of activity of rutin isolated from Tontelea Micrantha leaves against Vero and BHK, Fungi, Bacteria and Mayaro virus and its in silico activity.
(2020) Nizer, Waleska Stephanie da Cruz; Ferraz, Ariane Coelho; Moraes, Thaís de Fátima Silva; Ferreira, Fernanda Lopes; Magalhães, Cíntia Lopes de Brito; Vieira Filho, Sidney Augusto; Duarte, Lucienir Pains; Magalhães, José Carlos de
This work aimed to evaluate the antibacterial, antifungal, and anti-Mayaro virus (MAYV) activity of rutin, a flavonoid isolated from the leaves of Tontelea micrantha (Celastraceae). Materials and Methods: The antibacterial and antifungal activities were evaluated by the broth microdilution method through the determination of the minimum inhibitory concentration. The anti-MAYV activity was determined by the rutin concentration required to protect 50% of the cells after viral infection. The indirect 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay was used to determine the cytotoxic concentration of rutin to 50% of Vero and BHK cells. The antimicrobial activity spectrum of rutin was predicted using the online software prediction of activity spectra for substances (PASS). Results: Although the PASS prediction had shown that a higher probability of rutin acts as an antifungal agent, the in vitro assays showed no antimicrobial activity. Regarding the cytotoxicity assay, rutin was not toxic to Vero and BHK cells. Conclusions: Many biological activities have been described for flavonoids, but the flavone rutin did not show antimicrobial activity in vitro. The results obtained in this work suggest that rutin is not a promising antimicrobial agent.
Mayaro virus induction of oxidative stress is associated with liver pathology in a non-lethal mouse model.
(2019) Caetano, Camila Carla da Silva; Camini, Fernanda Caetano; Almeida, Letícia Trindade; Ferraz, Ariane Coelho; Silva, Tales Fernando da; Lima, Rafaela Lameira Souza; Carvalho, Mayara Medeiros de Freitas; Castro, Thalles de Freitas; Carneiro, Cláudia Martins; Silva, Breno de Mello; Silva, Silvana de Queiroz; Magalhães, José Carlos de; Magalhães, Cíntia Lopes de Brito
Mayaro virus (MAYV) causes Mayaro fever in humans, a self-limiting acute disease, with persistent arthralgia and arthritis. Although MAYV has a remerging potential, its pathogenic mechanisms remain unclear. Here, we characterized a model of MAYV infection in 3–4-week BALB/c mice. We investigated whether the liver acts as a site of viral replication and if the infection could cause histopathological alterations and an imbalance in redox homeostasis, culminating with oxidative stress. MAYV-infected mice revealed lower weight gain; however, the disease was self-resolving. High virus titre, neutralizing antibodies, and increased levels of aspartate and alanine aminotransferases were detected in the serum. Infectious viral particles were recovered in the liver of infected animals and the histological examination of liver tissues revealed significant increase in the inflammatory infiltrate. MAYV induced significant oxidative stress in the liver of infected animals, as well as a deregulation of enzymatic antioxidant components. Collectively, this is the first study to report that oxidative stress occurs in MAYV infection in vivo, and that it may be crucial in virus pathogenesis. Future studies are warranted to address the alternative therapeutic strategies for Mayaro fever, such as those based on antioxidant compounds.
Methanol extract and N,N-dimethyltryptamine from psychotria viridis ruiz & pav. inhibit in vitro the Zika virus infection.
(2021) Moraes, Thaís de Fátima Silva; Ferraz, Ariane Coelho; Nizer, Waleska Stephanie da Cruz; Tótola, Antônio Helvécio; Soares, Débora Barbosa da Silva; Duarte, Lucienir Pains; Vieira Filho, Sidney Augusto; Magalhães, Cíntia Lopes de Brito; Magalhães, José Carlos de
Zika virus (ZIKV) is a public health problem due to its association with serious fetal and neurological complications and the lack of antiviral agents and licensed vaccines against this virus. Surveillance studies have alerted about the potential occurrence of a new South American epidemic episode due to the recent circulation of an African ZIKV strain detected in Brazil. Therefore, it is essential to discover antiviral agents, including natural substances, that are capable of neutralizing the action of ZIKV. Several Psychotria species have antimicrobial and anti-infammatory properties. Thus, a methanol extract and dimethyltryptamine from Psychotria viridis were evaluated for their ability to inhibit ZIKV infection in vitro by measur- ing the efective concentration that protects 50% of cells and investigating their possible mechanisms of action. The tested samples showed antiviral activity against ZIKV. The extract showed virucidal activity, afecting viral and non-cellular ele- ments, inactivating the virus before infection or when it becomes extracellular after the second cycle of infection. It was also observed that both extract and dimethyltryptamine could inhibit the virus at intracellular stages of the viral cycle. In addition to dimethyltryptamine, it is believed that other compounds also contribute to the promising virucidal efect observed for the methanol extract. To our knowledge, this is the frst report of the activity of a methanolic extract and dimethyltryptamine from Psychotria viridis against cellular ZIKV infection. These two samples, extracted from natural sources, are potential candidates for use as antiviral drugs to inhibit ZIKV infections.
Netzahualcoyonol from Salacia multiflora (Lam.) DC. (Celastraceae) roots as a bioactive compound against gram-positive pathogens.
(2022) Nizer, Waleska Stephanie da Cruz; Ferraz, Ariane Coelho; Moraes, Thaís de Fátima Silva; Lima, William Gustavo de; Santos, Josana Pereira dos; Duarte, Lucienir Pains; Magalhães, Cíntia Lopes de Brito; Vieira Filho, Sidney Augusto; Magalhães, José Carlos de
The expression of virulence factors, such as biofilm formation, in association with the acquisition of resistance to multiple drugs, has evidenced the need for new and effective antimicrobial agents against Staphylococcus aureus. The evaluation of the pharmacological properties of plant-derived compounds is a promising alternative to the development of new antimicrobials. In this study, we aimed to evaluate the antibacterial, antibiofilm, and the synergistic and cytotoxic effects of netzahualcoyonol isolated from Salacia multiflora (Lam.) DC. roots. Netzahualcoyonol presented bacteriostatic (1.56–25.0 mg/mL) and bactericidal (25.0–400.0 mg/mL) effects against Gram-positive bacteria, disrupted the biofilm of S. aureus, and presented a synergistic effect after its combination with b-lactams and aminoglycosides. The low cytotoxicity of netzahualcoyonol (Selectivity Index (SI) for S. aureus (2.56), S. saprophyticus (20.56), and Bacillus subtilis (1.28)) suggests a good security profile. Taken together, these results show that netzahualcoyonol is promising for the development of a new effective antibacterial agent.
Pristimerin isolated from Salacia crassifolia (Mart. Ex. Schult.) G. Don. (Celastraceae) roots as a potential antibacterial agent against Staphylococcus aureus.
(2021) Nizer, Waleska Stephanie da Cruz; Ferraz, Ariane Coelho; Moraes, Thaís de Fátima Silva; Lima, William Gustavo de; Santos, Josana Pereira dos; Duarte, Lucienir Pains; Ferreira, Jaqueline Maria Siqueira; Magalhães, Cíntia Lopes de Brito; Vieira Filho, Sidney Augusto; Andrade, Ana Cláudia dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Abrahão, Jônatas Santos; Magalhães, José Carlos de
Ethnopharmacological relevance: Pristimerin is a triterpenoid considered the main component of Salacia crassifolia extracts. This terpene has shown promising antitumor, anti-inflammatory, and antimicrobial effects. Likewise, S. crassifolia has been used in traditional medicine to treat cancer and as an antimicrobial and anti-inflammatory agent. Aim of the study: This study aimed to evaluate the antibacterial activity of the hexane extract of Salacia crassifolia roots (HER) and its isolate, pristimerin, against pathogenic bacteria. Materials and methods: First, we evaluated the spectrum of action of HER and pristimerin by the determination of the minimum inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC). Subsequently, we analyzed the time-kill curve of these plant-derived compounds against Staphylococcus aureus. Then, we examined their mode of action by three different assays: the crystal violet methodology, the release of intracellular material, and transmission electron microscopy methods (TEM). Finally, we evaluated the effect of HER and pristimerin on the pre-formed biofilm of S. aureus by the crystal violet assay, the synergistic effect by the checkerboard method, the cytotoxicity against Vero cells, and the in silico activity using the online software PASS. Results: HER and pristimerin presented a narrow spectrum of action against Gram-positive bacteria (MIC 0.195–25 μg/mL), and their primary mode of action is the alteration of membrane permeability of S. aureus. Our results show that the compounds disrupted the pre-formed biofilm of S. aureus in a dose-dependent manner. Furthermore, HER and pristimerin presented a significant synergic effect after the combination with well-known antibiotics, which was associated with the ability of these phytomedicines to change membrane permeability. Regarding the cytotoxic effect, the selective index (SI) of HER ranged from 0.37 to 11.86, and the SI of pristimerin varied from 0.24 to 30.87, according to the bacteria tested. Conclusions: Overall, HER and pristimerin showed a promising antibacterial effect in vitro through the alteration of membrane permeability of S. aureus.
Virucidal activity of proanthocyanidin against Mayaro virus.
(2019) Ferraz, Ariane Coelho; Moraes, Thaís de Fátima Silva; Nizer, Waleska Stephanie da Cruz; Santos, Michelli dos; Tótola, Antônio Helvécio; Ferreira, Jaqueline Maria Siqueira; Vieira Filho, Sidney Augusto; Rodrigues, Vanessa Gonçalves; Duarte, Lucienir Pains; Magalhães, Cíntia Lopes de Brito; Magalhães, José Carlos de
Mayaro virus (MAYV) is a sublethal arbovirus transmitted by mosquitoes with possible installation of an urban cycle in the Americas. Its infection causes disabling arthralgia, and still, there is no vaccine or treatment to it. We recently investigated nearly 600 compounds by molecular docking and identified epicatechin as a potent antiviral against MAYV. The root extract of Maytenus imbricata showed anti-MAYV activity and two isolated compounds from this plant were also evaluated in vitro. Proanthocyanidin (PAC), a dimer containing epicatechin, showed an effective concentration for 50% of the cells infected by MAYV (EC50) of 37.9 ± 2.4 μM and a selectivity index (SI) above 40. PAC showed significant virucidal activity, inhibiting 100% of the virus proliferation (7 log units), and caused moderate effect during adsorption and virus internalization stage. However, PAC was unable to block the infection when only the cells were pretreated. It was observed a reduction in virus yields when adding PAC at different moments after infection. The set of results indicates that PAC binds to viral and non-cellular elements and may inactivate the MAYV. The inactivation occurs before infection or when the virus reaches the extracellular environment from the 2nd cycle of infection that could block its progression cellto-cell or to tissues not yet infected.
Virucidal antiviral activity of Maytenus quadrangulata extract against Mayaro virus : evidence for the presence of catechins.
(2023) Nunes, Damiana Antônia de Fátima; Lopes, Gabriela Francine Martins; Nizer, Waleska Stephanie da Cruz; Aguilar, Mariana Guerra de; Santos, Felipe Rocha da Silva; Sousa, Grasiely Faria de; Ferraz, Ariane Coelho; Duarte, Lucienir Pains; Brandão, Geraldo Célio; Vieira Filho, Sidney Augusto; Magalhães, Cíntia Lopes de Brito; Ferreira, Jaqueline Maria Siqueira; Magalhães, José Carlos de
Ethnopharmacological relevance: Mayaro virus (MAYV) is an arbovirus endemic to the Amazon region, which comprises the states of the North and Midwest region of Brazil and encompasses the largest tropical forest in the world, the Amazon Forest. The confirmation of its potential transmission by Aedes aegypti and recent cases in Brazil, mainly in large centers in the northern region, led to the classification of Mayaro fever as an emerging disease. Traditional medicine is commonly used to treat various diseases, mainly by local riverside populations. Some species of the genus Maytenus, which have similar morphologies, are popularly used to treat infections and inflammations. In this context, our research group has studied and confirmed the antiviral activity of several plant-derived compounds. However, several species of this same genus have not been studied and therefore deserve attention. Aim of the study: This study aimed to demonstrate the effects of ethyl acetate extracts of leaves (LAE) and branches (TAE) of Maytenus quadrangulata against MAYV. Materials and methods: Mammalian cells (Vero cells) were used to evaluate the cytotoxicity of the extracts. After cell infection by MAYV and the treatment with the extracts, we evaluated the selectivity index (SI), the virucidal effect, viral adsorption and internalization, and the effect on viral gene expression. The antiviral action was confirmed by quantifying the viral genome using RT-qPCR and by analyzing the effect on virus yield in infected cells. The treatment was performed based on the effective concentration protective for 50% of the infected cells (EC50). Results: The leaves (LAE; EC50 12.0 μg/mL) and branches (TAE; EC50 101.0 μg/mL) extracts showed significative selectivity against the virus, with SI values of 79.21 and 9.91, respectively, which were considered safe. Phytochemical analysis revealed that the antiviral action was associated with the presence of catechins, mainly in LAE. This extract was chosen for the subsequent studies since it reduced the viral cytopathic effect and virus production, even at high viral loads [MOI (multiplicity of infection) 1 and 5]. The effects of LAE resulted in a marked reduction in viral gene expression. The viral title was drastically reduced when LAE was added to the virus before infection or during replication stages, reducing virus production up to 5-log units compared to infected and untreated cells.
Zika virus induces oxidative stress and decreases antioxidant enzyme activities in vitro and in vivo.
(2020) Almeida, Letícia Trindade; Ferraz, Ariane Coelho; Caetano, Camila Carla da Silva; Menegatto, Marília Bueno da Silva; Andrade, Ana Cláudia dos Santos Pereira; Lima, Rafaela Lameira Souza; Camini, Fernanda Caetano; Pereira, Samille Henriques; Pereira, Karla Yanca da Silva; Silva, Breno de Mello; Perucci, Luiza Oliveira; Silva, André Talvani Pedrosa da; Magalhães, José Carlos de; Magalhães, Cíntia Lopes de Brito
The first outbreak of Zika virus (ZIKV) infection in the Americas, especially in Brazil, was reported in 2015. Fever, headache, rash, and conjunctivitis are the common symptoms of ZIKV infection. Unexpected clinical outcomes, such as microcephaly and Guillain-Barré syndrome, have also been reported. The recent spread of ZIKV and its association with severe illness has created an urgent need to understand its pathogenesis and find potential therapeutic targets. Studies show that some viruses, including Flavivirus, trigger oxidative stress, which affects cellular metabolism, viral cycle, and pathogenesis. However, the role of oxidative stress in ZIKV infection needs to be investigated. Here, we analyzed ZIKV infection-triggered oxidative stress and modified antioxidant enzyme activities. U87-MG and HepG2 cells were infected to measure reactive oxygen species (ROS), malondialdehyde (MDA), and carbonyl protein levels, the activities of superoxide dismutase (SOD) and catalase (CAT), and the activation of nuclear factor erythroid 2p45-related factor 2 (Nrf2). ZIKV infection induced a significant increase in ROS, lipid peroxidation, and protein carbonylation products and a significant decrease in SOD and CAT activities accompanied by inhibition of Nrf2 activation in both cell lines. Further, MDA and carbonyl protein levels and SOD and CAT activities were evaluated in the brain and liver of ZIKV-infected C57BL/6 mice, and oxidative stress associated with antioxidant depletion was also found to occur in vivo. Together, our findings indicate the potential use of antioxidants as a novel therapeutic approach to Zika disease, and future studies in this direction are warranted.