Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 91
Filtrar
1.
Molecules ; 29(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38792166

RESUMO

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic, or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity to exploit innovative solutions against these hazards. Recently, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs was evaluated against the non-enveloped RNA viruses, hepatitis A virus (HAV) and murine norovirus (MNV), a surrogate for human norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. The results showed that almost all peptides displayed virucidal effects, with about 90% of infectivity reduction in HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles causing their damage or hindering the recognition of cellular receptors. Hence, RiLK1 could represent a versatile antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.


Assuntos
Antivirais , Doenças Transmitidas por Alimentos , Norovirus , Antivirais/farmacologia , Antivirais/química , Animais , Doenças Transmitidas por Alimentos/prevenção & controle , Doenças Transmitidas por Alimentos/tratamento farmacológico , Doenças Transmitidas por Alimentos/virologia , Norovirus/efeitos dos fármacos , Humanos , Camundongos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Vírus da Hepatite A/efeitos dos fármacos , Viroses/tratamento farmacológico , Testes de Sensibilidade Microbiana
2.
Int J Toxicol ; 43(4): 368-376, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38501993

RESUMO

In a 3-month toxicity study in cynomolgus monkeys at a European contract laboratory, animals were infected with HAV, initially resulting in hepatic injury being incorrectly attributed to the test compound. Elevated serum ALT/AST/GLDH (5- to 10-fold) were noted in individual animals from all groups including controls, with no apparent dose, exposure, or time-related relationship. Liver histopathology revealed minimal to slight inflammatory cell accumulation in periportal zones of most animals, and minimal to slight hepatocyte degeneration/necrosis in 10/42 animals from all groups. As these findings were more pronounced in 6 drug-treated animals, including 2/6 in the low dose group, the draft report concluded: "treatment-related hepatotoxicity at all dose levels precluded determination of a NOAEL." However, the unusual pattern of hepatotoxicity suggested a factor other than drug exposure might have caused the hepatic effects. Therefore, snap-frozen liver samples were tested for hepatitis viruses using a PCR method. Tests for hepatitis B, C, and E virus were negative; however, 20/42 samples were positive for hepatitis A virus (HAV). Infection was strongly associated with increased serum ALT/GLDH, and/or hepatocyte degeneration/necrosis. Re-evaluation of the study in light of these data concluded that the hepatic injury was not drug-related. A subsequent 6-month toxicology study in HAV-vaccinated cynomolgus monkeys confirmed the absence of hepatotoxicity. Identification of HAV infection supported progression of the drug candidate into later clinical trials. Although rarely investigated, subclinical HAV infection has occasionally been reported in laboratory primates, including those used for toxicology studies and it may be more prevalent than the literature indicates.


Assuntos
Hepatite A , Fígado , Macaca fascicularis , Animais , Masculino , Fígado/efeitos dos fármacos , Fígado/patologia , Feminino , Vírus da Hepatite A/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , Alanina Transaminase/sangue , Testes de Toxicidade
3.
J Virol ; 97(2): e0198722, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36728416

RESUMO

Hepatitis A virus (HAV) infection often causes acute hepatitis, which results in a case fatality rate of 0.2% and fulminant hepatitis in 0.5% of cases. However, no specific potent anti-HAV drug is available on the market to date. In the present study, we focused on inhibition of HAV internal ribosomal entry site (IRES)-mediated translation and investigated novel therapeutic drugs through drug repurposing by screening for inhibitors of HAV IRES-mediated translation and cell viability using a reporter assay and cell viability assay, respectively. The initial screening of 1,158 drugs resulted in 77 candidate drugs. Among them, nicotinamide significantly inhibited HAV HA11-1299 genotype IIIA replication in Huh7 cells. This promising drug also inhibited HAV HM175 genotype IB subgenomic replicon and HAV HA11-1299 genotype IIIA replication in a dose-dependent manner. In the present study, we found that nicotinamide inhibited the activation of activator protein 1 (AP-1) and that knockdown of c-Jun, which is one of the components of AP-1, inhibited HAV HM175 genotype IB IRES-mediated translation and HAV HA11-1299 genotype IIIA and HAV HM175 genotype IB replication. Taken together, the results showed that nicotinamide inhibited c-Jun, resulting in the suppression of HAV IRES-mediated translation and HAV replication, and therefore, it could be useful for the treatment of HAV infection. IMPORTANCE Drug screening methods targeting HAV IRES-mediated translation with reporter assays are attractive and useful for drug repurposing. Nicotinamide (vitamin B3, niacin) has been shown to effectively inhibit HAV replication. Transcription complex activator protein 1 (AP-1) plays an important role in the transcriptional regulation of cellular immunity or viral replication. The results of this study provide evidence that AP-1 is involved in HAV replication and plays a role in the HAV life cycle. In addition, nicotinamide was shown to suppress HAV replication partly by inhibiting AP-1 activity and HAV IRES-mediated translation. Nicotinamide may be useful for the control of acute HAV infection by inhibiting cellular AP-1 activity during HAV infection processes.


Assuntos
Vírus da Hepatite A , Niacinamida , Proteínas Proto-Oncogênicas c-jun , Humanos , Avaliação Pré-Clínica de Medicamentos , Hepatite A , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/fisiologia , Niacinamida/farmacologia , Biossíntese de Proteínas , Fator de Transcrição AP-1/genética , Replicação Viral/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun/genética
4.
J Virol ; 96(18): e0064622, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36040176

RESUMO

Hepatitis A virus (HAV) infection is a major cause of acute viral hepatitis worldwide. Furthermore, HAV causes acute liver failure or acute-on-chronic liver failure. However, no potent anti-HAV drugs are currently available in the clinical situations. There have been some reports that amantadine, a broad-spectrum antiviral, suppresses HAV replication in vitro. Therefore, we examined the effects of amantadine and rimantadine, derivates of adamantane, on HAV replication, and investigated the mechanisms of these drugs. In the present study, we evaluated the effects of amantadine and rimantadine on HAV HM175 genotype IB subgenomic replicon replication and HAV HA11-1299 genotype IIIA replication in cell culture infection systems. Amantadine and rimantadine significantly inhibited HAV replication at the post-entry stage in Huh7 cells. HAV infection inhibited autophagy by suppressing the autophagy marker light chain 3 and reducing number of lysosomes. Proteomic analysis on HAV-infected Huh7 cells treated by amantadine and rimantadine revealed the changes of the expression levels in 42 of 373 immune response-related proteins. Amantadine and rimantadine inhibited HAV replication, partially through the enhancement of autophagy. Taken together, our results suggest a novel mechanism by which HAV replicates along with the inhibition of autophagy and that amantadine and rimantadine inhibit HAV replication by enhancing autophagy. IMPORTANCE Amantadine, a nonspecific antiviral medication, also effectively inhibits HAV replication. Autophagy is an important cellular mechanism in several virus-host cell interactions. The results of this study provide evidence indicating that autophagy is involved in HAV replication and plays a role in the HAV life cycle. In addition, amantadine and its derivative rimantadine suppress HAV replication partly by enhancing autophagy at the post-entry phase of HAV infection in human hepatocytes. Amantadine may be useful for the control of acute HAV infection by inhibiting cellular autophagy pathways during HAV infection processes.


Assuntos
Amantadina , Autofagia , Vírus da Hepatite A , Hepatite A , Rimantadina , Replicação Viral , Amantadina/farmacologia , Amantadina/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Autofagia/efeitos dos fármacos , Linhagem Celular , Hepatite A/tratamento farmacológico , Anticorpos Anti-Hepatite A , Vírus da Hepatite A/efeitos dos fármacos , Humanos , Proteômica , Rimantadina/farmacologia , Rimantadina/uso terapêutico , Replicação Viral/efeitos dos fármacos
5.
Proc Natl Acad Sci U S A ; 119(28): e2204511119, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35867748

RESUMO

Despite excellent vaccines, resurgent outbreaks of hepatitis A have caused thousands of hospitalizations and hundreds of deaths within the United States in recent years. There is no effective antiviral therapy for hepatitis A, and many aspects of the hepatitis A virus (HAV) replication cycle remain to be elucidated. Replication requires the zinc finger protein ZCCHC14 and noncanonical TENT4 poly(A) polymerases with which it associates, but the underlying mechanism is unknown. Here, we show that ZCCHC14 and TENT4A/B are required for viral RNA synthesis following translation of the viral genome in infected cells. Cross-linking immunoprecipitation sequencing (CLIP-seq) experiments revealed that ZCCHC14 binds a small stem-loop in the HAV 5' untranslated RNA possessing a Smaug recognition-like pentaloop to which it recruits TENT4. TENT4 polymerases lengthen and stabilize the 3' poly(A) tails of some cellular and viral mRNAs, but the chemical inhibition of TENT4A/B with the dihydroquinolizinone RG7834 had no impact on the length of the HAV 3' poly(A) tail, stability of HAV RNA, or cap-independent translation of the viral genome. By contrast, RG7834 inhibited the incorporation of 5-ethynyl uridine into nascent HAV RNA, indicating that TENT4A/B function in viral RNA synthesis. Consistent with potent in vitro antiviral activity against HAV (IC50 6.11 nM), orally administered RG7834 completely blocked HAV infection in Ifnar1-/- mice, and sharply reduced serum alanine aminotransferase activities, hepatocyte apoptosis, and intrahepatic inflammatory cell infiltrates in mice with acute hepatitis A. These results reveal requirements for ZCCHC14-TENT4A/B in hepatovirus RNA synthesis, and suggest that TENT4A/B inhibitors may be useful for preventing or treating hepatitis A in humans.


Assuntos
Proteínas Cromossômicas não Histona , DNA Polimerase Dirigida por DNA , Vírus da Hepatite A , Hepatite A , Proteínas Intrinsicamente Desordenadas , RNA Nucleotidiltransferases , RNA Viral , Replicação Viral , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Proteínas Cromossômicas não Histona/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo , Hepatite A/tratamento farmacológico , Hepatite A/metabolismo , Hepatite A/virologia , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/genética , Vírus da Hepatite A/fisiologia , Humanos , Proteínas Intrinsicamente Desordenadas/metabolismo , Camundongos , Camundongos Mutantes , RNA Nucleotidiltransferases/metabolismo , RNA Viral/biossíntese , RNA Viral/genética , Receptor de Interferon alfa e beta/genética , Replicação Viral/efeitos dos fármacos
6.
Molecules ; 27(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35268642

RESUMO

Diseases caused by viruses are a global threat, resulting in serious medical and social problems for humanity. They are the main contributors to many minor and major outbreaks, epidemics, and pandemics worldwide. Over the years, medicinal plants have been used as a complementary treatment in a range of diseases. In this sense, this review addresses promising antiviral plants from Marajó island, a part of the Amazon region, which is known to present a very wide biodiversity of medicinal plants. The present review has been limited to articles and abstracts available in Scopus, Web of Science, Science Direct, Scielo, PubMed, and Google Scholar, as well as the patent offices in Brazil (INPI), United States (USPTO), Europe (EPO) and World Intellectual Property Organization (WIPO). As a result, some plants from Marajó island were reported to have actions against HIV-1,2, HSV-1,2, SARS-CoV-2, HAV and HBV, Poliovirus, and influenza. Our major conclusion is that plants of the Marajó region show promising perspectives regarding pharmacological potential in combatting future viral diseases.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Extratos Vegetais/química , Plantas Medicinais/química , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Brasil , COVID-19/virologia , HIV-1/efeitos dos fármacos , Vírus da Hepatite A/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação
7.
Viruses ; 13(10)2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34696330

RESUMO

The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide. It is transmitted mainly by direct contact with patients who have been infected or by ingesting contaminated water or food. The virus is endemic in low-income countries where sanitary and sociodemographic conditions are poor. Paradoxically, improving sanitary conditions in these countries, which reduces the incidence of HAV infections, can lead to more severe disease in susceptible adults. The populations of developed countries are highly susceptible to HAV, and large outbreaks can occur when the virus is spread by globalization and by increased travel and movement of foodstuffs. Most of these outbreaks occur among high-risk groups: travellers, men who have sex with men, people who use substances, and people facing homelessness. Hepatitis A infections can be prevented by vaccination; safe and effective vaccines have been available for decades. Several countries have successfully introduced universal mass vaccination for children, but high-risk groups in high-income countries remain insufficiently protected. The development of HAV antivirals may be important to control HAV outbreaks in developed countries where a universal vaccination programme is not recommended.


Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Vírus da Hepatite A/efeitos dos fármacos , Hepatite A/epidemiologia , Hepatite A/prevenção & controle , Surtos de Doenças/prevenção & controle , Hepatite A/tratamento farmacológico , Homossexualidade Masculina , Humanos , Incidência , Masculino , Fatores de Risco , Minorias Sexuais e de Gênero , Viagem
8.
Sci Rep ; 11(1): 18970, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556768

RESUMO

It is widely accepted that Hepatitis A virus (HAV) is responsible for liver failure and even death in older people and in people with other serious health issues; so, proposing new compounds with inhibitory activity can help to treated of these disease's. In current study, a new class of quinolines is proposed with inhibitor activity of the HAV proteinase. So, in the first step, fused quinoline derivatives has been synthesized in short reaction time (12.0 min) and high efficiency yields (94%) in presence of 1-carboxymethyl-2,3-dimethylimidazolium iodide ([cmdmim]I) ionic liquid catalyst using a new method. In the following, chemical reactivity and inhibitory activity of synthesized quinolines were evaluated in density functional theory (DFT) framework and molecular docking methodologies. High global softness (0.67 eV), low HOMOSWBNNT-LUMO4a gap (4.78 eV), and more negative adsorption energy (- 87.9 kJ mol-1) in these quinolines reveal that the 4a and 4b compounds have better delivery than other quinolines using SWBNNT as suitable carrier to target cells. Molecular docking shows that the best cavity of the HAV has - 134.2 kJ mol-1 interaction energy involving bonding and non-bonding interactions. In fact, these interactions are between fused quinolines with especial geometries and sidechain flexibility amino acids residues inside the best binding site of the HAV, as hydrogen bonding, steric, and electrostatic interactions. So, these interactions imply that proposed fused quinolines have good inhibitor activity for the HAV.


Assuntos
Proteases Virais 3C/antagonistas & inibidores , Antivirais/farmacologia , Hepatite A/tratamento farmacológico , Quinolinas/farmacologia , Antivirais/química , Antivirais/uso terapêutico , Hepatite A/virologia , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/enzimologia , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Quinolinas/química , Quinolinas/uso terapêutico , Relação Estrutura-Atividade
9.
J Hepatol ; 75(6): 1323-1334, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34331968

RESUMO

BACKGROUND & AIMS: Hepatitis A virus (HAV) is a common cause of enterically transmitted viral hepatitis. In non-immune individuals, infection results in typically transient but occasionally fulminant and fatal inflammatory liver injury. Virus-specific T cell frequencies peak when liver damage is at its zenith, leading to the prevalent notion that T cells exacerbate liver disease, as suspected for other hepatotropic virus infections. However, the overall contribution of T cells to the control of HAV and the pathogenesis of hepatitis A is unclear and has been impeded by a historic lack of small animal models. METHODS: Ifnar1-/- mice are highly permissive for HAV and develop pathogenesis that recapitulates many features of hepatitis A. Using this model, we identified HAV-specific CD8+ and CD4+ T cells by epitope mapping, and then used tetramers and functional assays to quantify T cells in the liver at multiple times after infection. We assessed the relationships between HAV-specific T cell frequency, viral RNA amounts, and liver pathogenesis. RESULTS: A large population of virus-specific T cells accumulated within the livers of Ifnar1-/- mice during the first 1-2 weeks of infection and persisted over time. HAV replication was enhanced and liver disease exacerbated when mice were depleted of T cells. Conversely, immunization with a peptide vaccine increased virus-specific CD8+ T cell frequencies in the liver, reduced viral RNA abundance, and lessened liver injury. CONCLUSION: These data show that T cells protect against HAV-mediated liver injury and can be targeted to improve liver health. LAY SUMMARY: Hepatitis A virus is a leading cause of acute viral hepatitis worldwide. T cells were thought to contribute to liver injury during acute infection. We now show that virus-specific T cells protect against infection and limit liver injury.


Assuntos
Hepatite A/prevenção & controle , Hepatopatias/prevenção & controle , Linfócitos T/metabolismo , Análise de Variância , Animais , Modelos Animais de Doenças , Hepatite A/tratamento farmacológico , Hepatite A/epidemiologia , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/patogenicidade , Hepatopatias/tratamento farmacológico , Hepatopatias/epidemiologia , Camundongos , North Carolina , Estatísticas não Paramétricas , Linfócitos T/fisiologia
10.
Food Environ Virol ; 13(2): 241-247, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33689143

RESUMO

Seeking a means of sanitizing berries, the effectiveness of steady state levels of gaseous chlorine dioxide (ClO2) against hepatitis A virus (HAV) on laboratory-contaminated berries was determined. The generated ClO2 was maintained with 1 or 2 mg/l air inside a 269-l glove box to treat 50 g batches of blueberries, raspberries, and blackberries, and 100 g batches of strawberries that were immersion coated with HAV. Normalized data for ClO2 (ppm-h/g product) is reported as a function of ClO2 concentration, treatment time, and weight of treated product. Treatments of ClO2 ranging from 1.00 to 6.27 ppm-h/g berry were evaluated. When compared to untreated HAV-contaminated berries, log reductions of HAV were > 2.1 for all berry types and conditions tested indicating the gaseous ClO2 was effective. The average log reduction with strawberries, raspberries, blueberries and blackberries treated with 1.00 ppm-h/g, the lowest ClO2 treatment tested, were 2.44, 2.49, 3.23, and 3.45, respectively. The highest treatment of 6.27 ppm-h/g was applied at two different gas concentrations of 1 mg/l and 2 mg/l. Average log reductions for blueberries and strawberries treated with 6.27 ppm-h/g were 4.34 and 4.42, and 4.03 and 3.51, applied at 1 mg/l and 2 mg/l, respectively. For blackberries and raspberries 3.20 and 3.24, and 3.23 and 3.97 log reductions were observed for 6.27 ppm-h/g treatments applied at 1 mg/l and 2 mg/l, respectively. Results indicate that HAV contamination of berries can be substantially reduced by gaseous ClO2 and offer industry a waterless means of sanitizing berries against HAV.


Assuntos
Mirtilos Azuis (Planta)/virologia , Compostos Clorados/farmacologia , Conservação de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Fragaria/virologia , Vírus da Hepatite A/efeitos dos fármacos , Óxidos/farmacologia , Rubus/virologia , Compostos Clorados/química , Conservação de Alimentos/instrumentação , Conservantes de Alimentos/química , Frutas/virologia , Gases/química , Gases/farmacologia , Vírus da Hepatite A/crescimento & desenvolvimento , Óxidos/química
11.
Food Environ Virol ; 13(1): 107-116, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33501613

RESUMO

Enteric viruses, such as human norovirus (NoV) and hepatitis A virus (HAV), are the major causes of foodborne illnesses worldwide. These viruses have low infectious dose, and may remain infectious for weeks in the environment and food. Limited information is available regarding viral survival and transmission in low-moisture foods (LMF). LMFs are generally considered as ready-to-eat products, which undergo no or minimal pathogen reduction steps. However, numerous foodborne viral outbreaks associated with LMFs have been reported in recent years. The objective of this study was to examine the survival of foodborne viruses in LMFs during 4-week storage at ambient temperature and to evaluate the efficacy of advanced oxidative process (AOP) treatment in the inactivation of these viruses. For this purpose, select LMFs such as pistachios, chocolate, and cereal were inoculated with HAV and the norovirus surrogates, murine norovirus (MNV) and feline calicivirus (FCV), then viral survival on these food matrices was measured over a four-week incubation at ambient temperature, by both plaque assay and droplet-digital RT-PCR (ddRT-PCR) using the modified ISO-15216 method as well as the magnetic bead assay for viral recovery. We observed an approximately 0.5 log reduction in viral genome copies, and 1 log reduction in viral infectivity for all three tested viruses following storage of select inoculated LMFs for 4 weeks. Therefore, the present study shows that the examined foodborne viruses can persist for a long time in LMFs. Next, we examined the inactivation efficacy of AOP treatment, which combines UV-C, ozone, and hydrogen peroxide vapor, and observed that while approximately 100% (4 log) inactivation can be achieved for FCV, and MNV in chocolate, the inactivation efficiency diminishes to approximately 90% (1 log) in pistachios and 70% (< 1 log) in cereal. AOP treatment could therefore be a good candidate for risk reduction of foodborne viruses from certain LMFs depending on the food matrix and surface of treatment.


Assuntos
Chocolate/virologia , Grão Comestível/virologia , Conservação de Alimentos/métodos , Doenças Transmitidas por Alimentos/virologia , Vírus da Hepatite A/crescimento & desenvolvimento , Norovirus/crescimento & desenvolvimento , Pistacia/virologia , Inativação de Vírus/efeitos dos fármacos , Água/análise , Animais , Calicivirus Felino/efeitos dos fármacos , Calicivirus Felino/genética , Calicivirus Felino/crescimento & desenvolvimento , Calicivirus Felino/fisiologia , Chocolate/análise , Grão Comestível/química , Contaminação de Alimentos/análise , Conservação de Alimentos/instrumentação , Conservantes de Alimentos/química , Conservantes de Alimentos/farmacologia , Armazenamento de Alimentos , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/genética , Vírus da Hepatite A/fisiologia , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/farmacologia , Camundongos , Norovirus/efeitos dos fármacos , Norovirus/genética , Norovirus/fisiologia , Oxirredução , Ozônio/química , Ozônio/farmacologia , Pistacia/química
12.
Food Funct ; 12(4): 1498-1515, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33481979

RESUMO

The genus Foeniculum is known for its wide ethnobotanical use in the Mediterranean region. Herein, we explored the compositional differences of volatile oils and headspace aroma of Florence fennel (Foeniculum vulgare var. azoricum (Mill.) Thell.) based on its different organs and various geographical origins via gas chromatography coupled with mass spectrometry (GC-MS). Sixty-seven volatile components were detected with phenylpropenes and monoterpenes, including trans-anethole, limonene, α-pinene, trans-ß-ocimene, fenchyl acetate, and fenchone, as major constituents. Phenylpropenes were dominant in fennel hydro-distilled oils, whereas monoterpenes were dominant in most of the headspace aroma. The infraspecific variability was assessed using the unsupervised multivariate data analysis tools PCA and HCA, resulting in segregate clustering of accessions from different organs and locations with trans-anethole, limonene, trans-ß-ocimene, fenchone, myristicin, and apiole as major phytomarkers contributing to this segregation. The antiviral activities of samples against hepatitis A and C viruses were investigated using the plaque reduction assay, HAV 3C proteinase and HCV NS5B polymerase inhibitory assays with a percentage inhibition between 66% and 85% and IC50 values from 1.8 to 26.7 µg mL-1. In silico molecular docking scores in latter enzyme binding pockets revealed key allosteric interactions with trans-ß-ocimene and ß-fenchyl acetate showing the best Gibb's free energy. Florence fennel exhibited interesting new perspectives for medicinal and industrial applications.


Assuntos
Antivirais , Foeniculum/química , Óleos Voláteis , Óleos de Plantas , Antivirais/análise , Antivirais/química , Antivirais/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Hepacivirus/efeitos dos fármacos , Vírus da Hepatite A/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Óleos Voláteis/análise , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Óleos de Plantas/análise , Óleos de Plantas/química , Óleos de Plantas/farmacologia
13.
Carbohydr Res ; 500: 108246, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33516074

RESUMO

A novel series of nucleosides with potential antiviral activity have been synthesized and characterized using IR, MS, 1D NMR and 2D NMR data. The antiviral activity of the synthesized compounds was assessed against the Coxsackie B virus and Hepatitis A virus (HAV-10). The results revealed that compound 6 is equipotent to the standard drug Ribavirin against HAV-10. Also, some computational studies, such as the prediction of pharmacokinetic properties, toxicity, and bioactivity, have been done.


Assuntos
Antivirais/farmacologia , Teoria da Densidade Funcional , Enterovirus Humano B/efeitos dos fármacos , Vírus da Hepatite A/efeitos dos fármacos , Simulação de Acoplamento Molecular , Nucleosídeos/farmacologia , Triazinas/farmacologia , Antivirais/síntese química , Antivirais/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Nucleosídeos/síntese química , Nucleosídeos/química , Triazinas/síntese química , Triazinas/química
14.
Int J Biol Macromol ; 170: 94-106, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33358950

RESUMO

Considering the need of new lactic acid bacteria (LAB) for the production of novel biosurfactant (BS) molecules, the current study brings out a new insight on the exploration of cheese samples for BS producers and process optimization for industrial applications. In view of this, Lactobacillus plantarum 60FHE, Lactobacillus paracasei 75FHE, and Lactobacillus paracasei 77FHE were selected as the most operative strains. The biosurfactants (BSs) described as glycolipoproteins via Fourier-transform infrared spectroscopy (FTIR) exhibited antimicrobial activity against the food-borne pathogens. L. plantarum 60FHE BS showed an anticancer activity against colon carcinoma cells and had a week antiviral activity against Hepatitis A virus. Furthermore, glycolipoprotein production was enhanced by 1.42-fold through the development of an optimized process using central composite design (CCD). Emulsifying activities were stable after 60-min incubation from 4 to 120 °C, at pH 2-12, and after the addition of NaCl (2-14%). Characterization by nuclear magnetic resonance spectroscopy (1H NMR) revealed that BS produced from strain 60FHE was glycolipoprotein. L. plantarum produced mixed BSs determined by Liquid Chromatography/Mass Spectrometry (LC-MS). Thus, indicating that BS was applied as a microbial food prevention and biomedical. Also, L. plantarum 60FHE BS was achieved with the use of statistical optimization on inexpensive food wastes.


Assuntos
Anti-Infecciosos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Proteínas de Bactérias/isolamento & purificação , Queijo/microbiologia , Glicoproteínas/isolamento & purificação , Lactobacillus plantarum/química , Lipoproteínas/isolamento & purificação , Tensoativos/isolamento & purificação , Anti-Infecciosos/química , Anti-Infecciosos/economia , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/economia , Antineoplásicos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/economia , Proteínas de Bactérias/farmacologia , Linhagem Celular Tumoral , Cromatografia Líquida , Neoplasias do Colo/patologia , Glicoproteínas/química , Glicoproteínas/economia , Glicoproteínas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Vírus da Hepatite A/efeitos dos fármacos , Humanos , Lacticaseibacillus paracasei/química , Lacticaseibacillus paracasei/isolamento & purificação , Lactobacillus plantarum/isolamento & purificação , Lipoproteínas/química , Lipoproteínas/economia , Lipoproteínas/farmacologia , Espectrometria de Massas , Ressonância Magnética Nuclear Biomolecular , Filogenia , Ribotipagem , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química , Tensoativos/economia , Tensoativos/farmacologia , Resíduos/análise
15.
Viruses ; 12(5)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32408660

RESUMO

Hepatitis A virus (HAV) infection is one of the major causes of acute hepatitis, and this infection occasionally causes acute liver failure. HAV infection is associated with HAV-contaminated food and water as well as sexual transmission among men who have sex with men. Although an HAV vaccine has been developed, outbreaks of hepatitis A and life-threatening severe HAV infections are still observed worldwide. Therefore, an improved HAV vaccine and anti-HAV drugs for severe hepatitis A should be developed. Here, we reviewed cell culture systems for HAV infection, and other issues. This review may help with improving the HAV vaccine and developing anti-HAV drugs.


Assuntos
Antivirais/farmacologia , Técnicas de Cultura de Células/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Vírus da Hepatite A/fisiologia , Hepatite A/tratamento farmacológico , Animais , Hepatite A/prevenção & controle , Hepatite A/virologia , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/genética , Vírus da Hepatite A/imunologia , Humanos , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Vacinas Virais/imunologia
16.
Food Microbiol ; 90: 103461, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32336357

RESUMO

Human noroviruses (HNoV) and hepatitis A virus (HAV) are predominantly linked to foodborne outbreaks worldwide. As cell-culture systems to propagate HNoV in laboratories are not easily available, Tulane virus (TV) is used as a cultivable HNoV surrogate to determine inactivation. Heat-sensitization of HAV and TV by "generally recognized as safe'' (GRAS) substances can potentially reduce their time-temperature inactivation parameters during processing to ensure food safety. Curcumin, gingerol (from ginger), and grape seed extract (GSE) reportedly have anti-inflammatory, immune-modulating and antiviral properties. The objective of this study was to determine and compare the D-values and z-values of HAV and TV at 52-68 °C with or without curcumin (0.015 mg/ml), gingerol (0.1 mg/ml), or GSE (1 mg/ml) in 2-ml glass vials. HAV at ~7 log PFU/ml and TV at ~6 log PFU/ml were diluted in phosphate buffered saline (PBS) and added to two sets of six 2-mL sterile glass vials. One set served as the control and the second set had the three extracts individually added for thermal treatments in a circulating water bath for 0-10 min. The D-values for TV in PBS ranged from 4.55 ± 0.28 to 1.08 ± 0.16 min, and for HAV in PBS ranged from to 9.21 ± 0.24 to 0.67 ± 0.19 min at 52-68 °C. Decreased D-values (52-58 °C) for TV with curcumin ranging from 4.32 ± 0.25 to 0.62 ± 0.17 min, gingerol from 4.09 ± 0.18 to 0.72 ± 0.09 min and GSE from 3.82 ± 0.18 to 0.80 ± 0.07 min, with similar trends for HAV were observed. The linear model showed significant differences (p < 0.05) between the D-values of HAV and TV with and without plant extracts for most tested temperatures. This suggests that GRAS substances can potentially lower temperature and time regimens needed to inactivate HAV and TV.


Assuntos
Antivirais/farmacologia , Microbiologia de Alimentos/métodos , Vírus da Hepatite A/efeitos dos fármacos , Temperatura Alta , Norovirus/efeitos dos fármacos , Inativação de Vírus/efeitos dos fármacos , Catecóis/farmacologia , Curcumina/farmacologia , Álcoois Graxos/farmacologia , Extrato de Sementes de Uva/farmacologia , Vírus da Hepatite A/fisiologia , Norovirus/fisiologia
17.
Sci Rep ; 10(1): 5998, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32265465

RESUMO

Microbial fermentation of plant material alters the composition of volatile and non-volatile plant natural products. We investigated the antioxidant, anticancer, and antiviral properties of extracts of defatted soybean meal fermented with Aspergillus fumigatus F-993 or A. awamori FB-133 using in vitro methods. Gas chromatography-mass spectrometry analysis of soybean meal fermented with A. awamori FB-133 and A. fumigatus F-993 identified 26 compounds with 11,14-octadecadienoic acid and methyl ester (63.63%) and 31 compounds with butylated hydroxytoluene (66.83%) and δ-myrcene (11.43%) as main constituents, respectively. The antioxidant activities of DSM extract were 3.362 ± 0.05 and 2.11 ± 0.02 mmol TE/mL, FDSM treated with A. awamori FB-133 were 4.763 ± 0.05 and 3.795 ± 0.03 mmol TE/mL and FDSM treated with A. fumigatus F-993 were 4.331 ± 0.04 and 3.971 ± 0.02 mmol TE/mL as determined by ABTS and FRAP assays, respectively. Both fermented extracts had better antioxidant activity than the unfermented extract as shown by multiple antioxidant activity assays. The concentration of fermented extracts required for 50% inhibition of cell viability was significantly lower than that of the unfermented extract when tested against the human liver cancer cell line HepG2 as shown by cell viability assays, indicating strong anticancer activity. The IC50 values for DSM, FDSM with A. fumigatusF-993 and FDSM with A. awamori FB-133 were27, 16.88 and 8.60 µg/mL, respectively. The extract of FDSM with A. awamori FB-133 showed the strongest anticancer activity, compared to DSM and FDSM with A. FumigatusF-993 extracts. Fermented extracts also reduced hepatitis A virus titres to a greater extent than unfermented extracts, thus showing strong antiviral property. Hepatitis A virus titres were reduced by 2.66 and 3 log10/0.1 mL by FDSM with A. fumigatusF-993 and FDSM by A.awamori FB-133, respectively, compared to DSM (5.50 log10/0.1 mL). Thus, the fermentation of soybean meal with A. fumigatusF-993 or A. awamori FB-133 improves the therapeutic effect of soybean extracts, which can be used in traditional medicine.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Antioxidantes/metabolismo , Antivirais/metabolismo , Fermentação , Aromatizantes/metabolismo , Glycine max/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Antivirais/farmacologia , Aspergillus fumigatus/metabolismo , Reatores Biológicos , Aromatizantes/farmacologia , Células Hep G2 , Hepatite A/tratamento farmacológico , Vírus da Hepatite A/efeitos dos fármacos , Humanos
18.
Chem Biodivers ; 17(2): e1900511, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31800173

RESUMO

The in vitro cytotoxic activity in Vero cells and the antiviral activity of Erythrina speciosa methanol extract, fractions, and isolated vitexin were studied. The results revealed that E. speciosa leaves ethyl acetate soluble fraction of the methanol extract (ESLE) was the most active against herpes simplex virus type 1 (HSV-1). Bioactivity-guided fractionation was performed on ESLE to isolate the bioactive compounds responsible for this activity. One sub-fraction from ESLE (ESLE IV) showed the highest activity against HSV-1 and Hepatitis A HAV-H10 viruses. Vitexin isolated from ESLE VI exhibited a significant antiviral activity (EC50 =35±2.7 and 18±3.3 µg/mL against HAV-H10 and HSV-1 virus, respectively), which was notably greater than the activity of the extract and the fractions. Molecular docking studies were carried out to explore the molecular interactions of vitexin with different macromolecular targets. Analysis of the in silico data together with the in vitro studies validated the antiviral activity associated with vitexin. These outcomes indicated that vitexin is a potential candidate to be utilized commendably in lead optimization for the development of antiviral agents.


Assuntos
Antivirais/metabolismo , Apigenina/metabolismo , Erythrina/química , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Antivirais/química , Antivirais/farmacologia , Apigenina/química , Apigenina/farmacologia , Sítios de Ligação , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , DNA Polimerase Dirigida por DNA/química , DNA Polimerase Dirigida por DNA/metabolismo , Erythrina/metabolismo , Frutas/química , Frutas/metabolismo , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/metabolismo , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/metabolismo , Proteínas Virais/química , Proteínas Virais/metabolismo
19.
Int J Med Sci ; 16(10): 1366-1370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692913

RESUMO

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis including acute liver failure. Hepatitis B infection (HBV) occurs worldwide, with the highest rates in Asian and African countries, and there are several reports that HAV infection may have a more severe clinical course in patients with chronic HBV infection. We previously demonstrated that Japanese miso extracts have inhibitory effects on HAV replication. In the present study, we examined the replication of HAV and HBV in a hepatocyte superinfection model and the inhibitory effects of Japanese miso extracts on both viruses. According to the results, HAV infection inhibited HBV replication in superinfected hepatocytes, and Japanese rice-koji miso extracts had inhibitory effects on HAV replication. Our findings provide useful information for clinicians in managing HAV infection in patients with chronic HBV infection.


Assuntos
Hepatite A/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Extratos Vegetais/farmacologia , Superinfecção/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Hepatite A/complicações , Hepatite A/virologia , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/patogenicidade , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Hepatócitos/virologia , Humanos , Oryza/química , Extratos Vegetais/uso terapêutico , Glycine max/química , Superinfecção/complicações , Superinfecção/virologia
20.
Carbohydr Polym ; 226: 115261, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582052

RESUMO

The main objective of this work to explore new safe antiviral agents against hepatitis A virus (HAV), norovirus (NoV) and Coxsackievirus B4 (CoxB4) infections. In this context, we have successfully prepared new polyquaternary phosphonium oligochitosans (PQPOC1,2) to use them as natural synergistic in-situ bioreductants of silver ions into nanosilver and stabilizing agent for these nanosilver to fabricate PQPOCs-AgNPs nano-biocomposites (NBC1,2). The antiviral performance of the PQPOCs and NBCs against FCV, HAV, and CoxB4 reflects great virucidal activities for NBCs as compared with PQPOCs with maximum viral reduction% (41.42, 80.62, and 84.04%) for NBC1 against FCV, HAV, and CoxB4, respectively. Furthermore, the antiviral activity of NBC1 is concentration- / pH-dependent where NBC1 acquired its maximum antiviral at [NBC1] = 200 µL/mL and pH 4. Based upon these facts, we could attribute the enhanced virucidal efficacy of NBC1: (i) binding of AgNPs to the virions active sites. (ii) Electrostatic interaction between the positive brushes of PQPOC and negative targets of viruses. (iii) Inducing ribonuclease catalyzed by CS to degrade the viral RNA and consequently prevents its transcription and translation.


Assuntos
Antivirais , Quitina/análogos & derivados , Enterovirus/efeitos dos fármacos , Vírus da Hepatite A/efeitos dos fármacos , Nanocompostos/química , Norovirus/efeitos dos fármacos , Prata/farmacologia , Antivirais/síntese química , Antivirais/química , Antivirais/farmacologia , Quitina/síntese química , Quitina/química , Quitina/farmacologia , Quitosana , Oligossacarídeos , Prata/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...