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1.
Electron. j. biotechnol ; 50: 16-22, Mar. 2021. ilus, tab
Article in English | LILACS | ID: biblio-1292419

ABSTRACT

BACKGROUND: Cecropin P1, acting as an antimicrobial, has a broad-spectrum antibacterial activity with some antiviral and antifungal properties. It is a promising natural alternative to antibiotics which is originally isolated from the pig intestinal parasitic nematode Ascaris suum. Many studies have shown that Cecropin P1 is helpful for the prevention or treatment of clinical diseases. Therefore, it is very necessary to establish a safe, nontoxic, and efficient expression method of Cecropin P1. RESULTS: The results indicated that the recombinant protein was about 5.5 kDa showed by Tricine­SDS­ PAGE and Western blot. And Cecropin P1 was efficiently secreted and expressed after 12 h of induction, with an increasing yield over the course of the induction. Its maximum concentration was 7.83 mg/L after concentration and purification. In addition, in vitro experiments demonstrated that Cecropin P1 not only exerted a strong inhibitory effect on Escherichia coli, Salmonella sp., Shigella sp., and Pasteurella sp., but also displayed an antiviral activity against PRRSV NADC30-Like strain. CONCLUSIONS: Collectively, the strategy of expressing Cecropin P1 in Saccharomyces cerevisiae is harmless, efficient, and safe for cells. In addition, the expressed Cecropin P1 has antiviral and antibacterial properties concurrently.


Subject(s)
Peptides/pharmacology , Saccharomyces cerevisiae/drug effects , Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Peptides/chemistry , In Vitro Techniques , Recombinant Proteins , Microbial Sensitivity Tests , Blotting, Western
2.
Braz. j. med. biol. res ; 54(7): e10240, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249316

ABSTRACT

Dengue is the most important arthropod-borne viral disease worldwide. Infection with any of the four dengue virus (DENV) serotypes can be asymptomatic or lead to disease with clinical symptoms ranging from undifferentiated and self-limiting fever to severe dengue disease, which can be fatal in some cases. Currently, no specific antiviral compound is available for treating DENV. The aim of this study was to identify compounds in plants from Paraguayan folk medicine with inhibitory effects against DENV. We found high virucidal activity (50% maximal effective concentration (EC50) value of 24.97 µg/mL) against DENV-2 in the ethanolic extract of the roots of Solanum sisymbriifolium Lam. (Solanaceae) without an evident cytotoxic effect on Vero E6 cells. Three saponins isolated from the root extract showed virucidal effects (EC50 values ranging from 24.9 to 35.1 µg/mL) against DENV-2. Additionally, the saponins showed inhibitory activity against yellow fever virus (EC50 values ranging from 126 to 302.6 µg/mL), the prototype virus of the Flavivirus genus, suggesting that they may also be effective against other members of this genus. Consequently, these saponins may be lead compounds for the development of antiviral agents.


Subject(s)
Saponins/pharmacology , Solanum , Dengue Virus , Antiviral Agents/pharmacology , Virus Replication , Yellow fever virus
3.
Article in Chinese | WPRIM | ID: wpr-879126

ABSTRACT

Isatidis Radix is the dried root of the Isatis indigotica, with pharmacological effects such as heat-clearing and detoxification, cooling blood and pharyngeal relief, antibacterial and anti-inflammatory effects. It is often used clinically to prevent and treat influenza and other diseases. In this paper, relevant domestic and foreign literatures in recent years were summarized, and it was found that Isatidis Radix lignans, indole alkaloids, polysaccharides, etc. were the main active components against influenza virus. Then its pharmacological effects and the mechanism of action were reviewed, providing a basis for in-depth research on the antiviral effect of Isatidis Radix.


Subject(s)
Antiviral Agents/pharmacology , Drugs, Chinese Herbal , Isatis , Orthomyxoviridae , Plant Roots , Polysaccharides
4.
Medwave ; 20(9): e8049, 30-10-2020.
Article in English, Spanish | LILACS | ID: biblio-1141141

ABSTRACT

En diciembre de 2019 una nueva especie de ß-coronavirus causante de neumonía fue identificada en la ciudad China de Wuhan, el cual posteriormente fue denominado SARS-CoV-2. Este virus de ácido ribonucleico presenta ciertas similitudes con otros virus del mismo material genético, dentro de ellos se ha visto que la infección por virus de la inmunodeficiencia humana se asemeja en diversos aspectos a la infección por SARS-CoV-2. En este comentario presentamos algunas de las similitudes virológicas, inmunológicas, clínicas y farmacológicas entre estos dos virus, las cuales podrían permitirnos entender de mejor manera la inmunopatogenia de COVID-19, así como también tomar algunas decisiones en cuanto al manejo antiviral.


In December 2019, a new species of pneumonia-causing betacoronavirus was identified in Wuhan, China, which was later identified as SARS-CoV-2. This RNA virus presents certain similarities with other viruses of the same genetic material. It has been seen that infection by human immunodeficiency virus resembles the infection by SARS-CoV-2 in various aspects. In this comment, we present some of the virological, immunological, clinical, and pharmacological similarities between HIV and SARS-CoV-2, which could allow us to understand the immunopathogenesis of COVID-19 better, as well as make some decisions in regarding antiviral management.


Subject(s)
Humans , HIV Infections/virology , HIV/isolation & purification , SARS-CoV-2/isolation & purification , COVID-19/virology , Antiviral Agents/pharmacology , HIV Infections/immunology , HIV/immunology , Pandemics , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/drug therapy
5.
Arq. gastroenterol ; 57(3): 267-271, July-Sept. 2020. tab, graf
Article in English | LILACS | ID: biblio-1131666

ABSTRACT

ABSTRACT BACKGROUND: Chronic hepatitis C still figures as an important cause of morbidity among the Brazilian population, and is closely associated with metabolic disturbances, including insulin resistance (IR), which can be evaluated by the Homeostatic Model Assessment (HOMA-IR). IR may entail lower sustained virologic response (SVR) on certain therapeutic regimens and faster progression to advanced hepatic fibrosis. With the arrival of the direct acting agents (DAA) in hepatitis C treatment, there is an increased need in observing the impact in patients' IR profile while using such therapies. OBJECTIVE: - 1) To compare the results of HOMA-IR in patients affected by chronic hepatitis C before treatment with DAA and 12 months after finishing it with SVR. 2) To evaluate the evolution of weight after curing chronic hepatitis C. METHODS: We included patients older than 18 from two tertiary care in Curitiba - PR, of both sexes, with chronic hepatitis C, treated with DAA, from July 2015 to September 2017. We also evaluated the patients' levels of fasting insulin, fasting glucose and glycated hemoglobin before starting treatment and 12 months after finishing it. We also used epidemiologic data, such as age, sex, hepatic fibrosis degree, body mass index, abdominal circumference, viral genotype and the presence of diabetes mellitus before and after treatment. IR was assessed before and after treatment and calculated by the HOMA-IR score. Insulin resistance was defined by a HOMA-IR greater than 2.5. We excluded patients who lost follow-up, those who did not achieve SRV and those who did not have a laboratory profile. The results of quantitative variables were described by means, medians, and standard deviations. P values <0.05 indicated statistical significance. RESULTS: We included 75 patients in this study, with a mean age of 55.2 years and 60% of males. Forty-three patients had advanced fibrosis. Twenty one (28%) had a previous diabetes mellitus diagnosis. We identified 31 (41.3%) patients with IR before antiviral treatment, and this number increased to 39 (52%) after 12 months of finishing treatment, according to HOMA-IR. There was no statistic difference between insulin, glucose and HOMA-IR measurements before and after curing hepatitis C. We observed a weight gain in patients shortly after curing hepatitis C, but this did not persist at the end of the study. We also had no significant difference in IR prevalence when viral genotype was concerned. CONCLUSION: In this study, there was no statistically significant difference between HOMA-IR results in patients before and 12 months after treatment for hepatitis C. Even though patients gained weight after the cure, this was not statistically significant after a year (P=0.131).


RESUMO CONTEXTO: A hepatite C crônica ainda figura como importante causa de morbimortalidade na população brasileira, e está associada a alterações metabólicas, incluindo a resistência insulínica (RI), que pode ser avaliada pelo índice HOMA-IR. A RI pode inclusive implicar em menores taxas de reposta virológica sustentada (RVS) em certos regimes terapêuticos e à uma mais rápida progressão para fibrose hepática avançada. Com o advento dos novos antivirais de ação direta (DAA) oferecidos para hepatite C, há crescente necessidade de observar o impacto dos mesmos no perfil de RI em pacientes submetidos à tais terapêuticas. OBJETIVO: - 1) Comparar os valores do HOMA-IR dos pacientes com hepatite C crônica antes do tratamento com os DAAS com os valores deste índice após 12 meses do término do tratamento com RVS. 2) Avaliar evolução do peso após obtenção da cura da hepatite C crônica. MÉTODOS: Foram incluídos pacientes maiores de 18 anos de dois serviços terciários de Curitiba - PR, de ambos os sexos, portadores de hepatite C crônica, com tratamento com os antivirais de ação direta, no período de julho de 2015 a setembro de 2017. Tais pacientes também foram submetidos a dosagem dos níveis de insulina de jejum, glicemia de jejum e hemoglobina glicada antes de iniciar o tratamento da hepatite C e até 12 meses após o término. Também foram utilizados dados como idade, sexo, grau de fibrose hepática, índice de massa corporal, circunferência abdominal, genótipo viral e presença de diabetes mellitus antes e depois do tratamento. A RI foi estimada antes e após 12 meses do término do tratamento e calculada pelo HOMA-IR. Os resultados de variáveis quantitativas foram descritos por médias, medianas, valores mínimos, valores máximos e desvios padrões. Valores de P<0,05 indicaram significância estatística. RESULTADOS: Foram incluídos 75 pacientes no estudo com média de idade de 55,2 anos, sendo 60% do sexo masculino. Destes pacientes, 43 tinham fibrose avançada. Vinte e um (28%) pacientes tinham o diagnóstico de diabetes mellitus. A RI foi observada em 31 (41,3%) pacientes antes do tratamento antiviral, sendo que este número aumentou para 39 (52%) de acordo com a dosagem do HOMA-IR 12 meses após o término do tratamento. Não houve diferença estatística entre os valores de insulina, glicemia e HOMA-IR antes e após a cura da hepatite. Houve um ganho de peso inicial após a obtenção da cura da hepatite C, mas que não se manteve ao final do estudo. CONCLUSÃO: Não foi vista diferença estatística significante entre os valores do HOMA-IR apresentados pelos pacientes portadores de hepatite C crônica antes do tratamento e 12 meses após a cura da doença. Embora tenha ocorrido ganho de peso após obtenção da cura da doença, este não se deu de forma estatisticamente significativa (P=0,131) ao final de um ano.


Subject(s)
Humans , Male , Female , Insulin Resistance , Hepatitis C, Chronic/drug therapy , Antiviral Agents/therapeutic use , Antiviral Agents/pharmacology , Ribavirin/therapeutic use , Brazil , Treatment Outcome , Hepacivirus/drug effects , Hepacivirus/genetics , Middle Aged
6.
Braz. j. med. biol. res ; 53(9): e10475, 2020. tab
Article in English | LILACS, ColecionaSUS | ID: biblio-1132550

ABSTRACT

SARS-CoV-2 has recently emerged, becoming a global threat, affecting directly all human beings owing to its morbidity and mortality and indirectly, due to the enormous economic and psychological impact produced by social isolation, the most effective measure so far, but unsustainable for a long period. The scientific effort to understand and control SARS-CoV-2 transmission and clinical impact has been huge, and important achievements are highlighted in this review. Diagnosis is central and is the first step in recognizing and fighting any infectious agent. Instrumental to that is the quality of the data, relying on serological and molecular surveys in addition to trustworthy clinical records. However, the fast spread of a virus adapted for human-to-human respiratory transmission raised a demand for millions of molecular tests that are simply not available. Several candidate drugs are under evaluation in clinical trials. Those with an already recognized safety profile are more auspicious, since, if proven effective, can cut several steps of production and phase 2 and 3 trials. More than one hundred vaccine prototypes are in different stages of development, however, safety and efficacy evaluations cannot be obviated, implicating, most optimistically, in at least months for us to have an effective immunization, the definite measure to allow a safe return to the pre-pandemic lifestyle. Science has never been more necessary and present in daily life. Relying on the best of human wit is the only way out to this pandemic, saving as many lives as possible.


Subject(s)
Humans , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Coronavirus Infections/epidemiology , Pandemics , Antiviral Agents/pharmacology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Pneumonia, Viral/epidemiology , Viral Vaccines , Clinical Trials as Topic , Drug Evaluation , Betacoronavirus , COVID-19 Vaccines , COVID-19
7.
Evid. actual. práct. ambul ; 23(2): e002057, 2020.
Article in Spanish | LILACS | ID: biblio-1103663

ABSTRACT

La pandemia de COVID-19 está generando información epidemiológica y clínica en una escala sin precedentes para una enfermedad de reciente aparición. Aunque ya se han iniciado numerosos ensayos clínicos de fármacos antiguos y nuevos como potenciales antivirales específicos, la mayor parte de la información publicada hasta ahora carece de los controles básicos para la evaluación de la eficacia de un medicamento. Los medios de comunicación amplifican estos resultados preliminares y suman presión a los médicos asistenciales y a los decisores de políticas públicas. Este artículo revisa las pruebas disponibles sobre los cuatro tratamientos antivirales específicos más prometedores: hidroxicloroquina, lopinavir/ritonavir, remdesvir e interferones alfa y beta. Se comprueba en todos ellos que no hay demostración suficiente de eficacia como para recomendar su uso fuera de una investigación experimental adecuadamente controlada. En el uso individual de un medicamento no hay forma de saber si está beneficiando o perjudicando al paciente. Es erróneo asumir que la eventual curación se debe al fármaco y un mal desenlace debe atribuirse a la enfermedad. Sólo la comparación entre grupos de pacientes asignados al tratamiento experimental o a un control adecuado permite conocer la eficacia y seguridad de las intervenciones. El desafío es conciliar la urgencia de actuar con la generación de nuevos conocimientos.Aunque no resulta sencillo organizar ensayos clínicos en este contexto, las instituciones pueden sumarse a los proyectos en marcha a nivel nacional e internacional. El uso de estos fármacos debe considerarse experimental, por lo que es necesario obtener el consentimiento informado del paciente. (AU)


The COVID-19 pandemic is generating epidemiological and clinical information on an unprecedented scale for a newly emerging disease. Although numerous clinical trials of old and new drugs as potential specific antivirals have already been started, most of the information published so far lacks basic controls for evaluating drug efficacy. The media amplify these preliminary results and add pressure to doctors and policymakers. This article reviews the available evidence for the four most promising specific antiviral treatments: hydroxychloroquine, lopinavir / ritonavir, remdesvir, and alpha and beta interferons. The findings show that none of them has sufficient demonstration of efficacy to recommend its use outside ofthe adequately controlled experimental study. In the individual use of a drug there is no way of knowing if it is benefiting orharming the patient. It is wrong to assume that the eventual cure is due to the drug and a poor outcome must be attributed to the disease. Only the comparison between groups of patients assigned to the experimental treatment or to an adequate control can establish the efficacy and safety of the interventions. The challenge is to reconcile the urgency to act with the generation of new knowledge. Although it is not easy to organize clinical trials in this context, the institutions can join theongoing projects at the national and international levels. The use of these drugs should be considered experimental, so it is necessary to obtain the informed consent of the patient. (AU)


Subject(s)
Humans , Antiviral Agents/pharmacology , Pneumonia, Viral/drug therapy , Interferons/pharmacology , Coronavirus Infections/drug therapy , Ritonavir/pharmacology , Lopinavir/pharmacology , Hydroxychloroquine/pharmacology , Antiviral Agents/adverse effects , Treatment Outcome , Azithromycin/pharmacology , Risk Assessment , Ritonavir/administration & dosage , Ritonavir/adverse effects , Evidence-Based Medicine/trends , Information Dissemination , Off-Label Use , Health Communication , Pandemics , Lopinavir/administration & dosage , Lopinavir/adverse effects , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Informed Consent
8.
Article in English | WPRIM | ID: wpr-881033

ABSTRACT

Coronavirus disease-2019 (COVID-19) is a new highly infectious disease caused by a novel coronavirus. Recently, the number of new cases infected pneumonia in the world continues to increase, which has aroused great concern from the international community. At present, there are no small-molecule specific anti-viral drugs for the treatment. The high mortality rate seriously threatens human health. Traditional Chinese medicine (TCM) is a unique health resource in China. The combination of TCM and Western medicine has played a positive and important role in combating COVID-19 in China. In this review, through literature mining and analysis, it was found that TCM has the potential to prevent and treat the COVID-19. Then, the network pharmacological studies demonstrated that TCM played roles of anti-virus, anti-inflammation and immunoregulation in the management of COVID-19 via multiple components acting on multiple targets and multiple pathways. Finally, clinical researches also confirmed the beneficial effects of TCM on the treatment of patients. This review may provide meaningful and useful information on further drug development of COVID-19 and other viral infectious diseases.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Humans , Medicine, Chinese Traditional/trends , SARS-CoV-2/drug effects
9.
Braz. j. microbiol ; 49(4): 785-789, Oct.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-974292

ABSTRACT

ABSTRACT Bovine viral diarrhea virus can cause acute disease in livestock, leading to economic losses. We show that Prostaglandin A1 inhibits bovine viral diarrhea virus replication in Madin-Darby bovine kidney cells (94% inhibition using 5 µg/mL). Light and electron microscopy of infected cells shows that Prostaglandin A1 also prevents virus-induced vacuolization, but at higher concentrations (10 µg/mL).


Subject(s)
Animals , Cattle , Antiviral Agents/pharmacology , Prostaglandins A/pharmacology , Bovine Virus Diarrhea-Mucosal Disease/virology , Diarrhea Viruses, Bovine Viral/drug effects , Antiviral Agents/analysis , Prostaglandins A/analysis , Virus Replication/drug effects , Bovine Virus Diarrhea-Mucosal Disease/drug therapy , Cell Line , Diarrhea Viruses, Bovine Viral/physiology , Diarrhea Viruses, Bovine Viral/genetics , Diarrhea
10.
Braz. j. infect. dis ; 22(6): 477-486, Nov.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-984016

ABSTRACT

ABSTRACT Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it "HepG2.RL1". Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection.


Subject(s)
Humans , Female , Middle Aged , Antiviral Agents/pharmacology , Virus Replication/drug effects , Hepatitis B virus/drug effects , Lamivudine/pharmacology , Cytidine/analogs & derivatives , DNA, Viral/chemistry , Microbial Sensitivity Tests , Cell Line , Hepatitis B virus/isolation & purification , Hepatitis B virus/physiology , Hepatocytes/virology , Drug Resistance, Viral/drug effects , Mutation
11.
Rev. Soc. Bras. Med. Trop ; 51(5): 584-590, Sept.-Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-957459

ABSTRACT

Abstract INTRODUCTION: The Mayaro virus (MAYV), which is an arbovirus closely related to the Chikungunya virus, causes a dengue-like acute illness that is endemic to Central and South America. We investigated the anti-MAYV activity of prostaglandin A1 (PGA1), a hormone which exhibits antiviral activity against both ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) viruses. Further, we examined the effects of inducting the stress protein HSP70 following PGA1 treatment. METHODS: Hep-2 cells infected with MAYV were treated with PGA1 (0.1-6μg/ml) 12h before infection and for different periods post-infection. Inhibition of viral replication inhibition was analyzed via viral titer determination, whereas the effect of PGA1 on viral morphogenesis was examined via transmission electron microscopy (TEM). Autoradiography (with 35S methionine labeling) and western blotting were used to assess the effect of PGA1 treatment on viral and cellular protein synthesis, and on HSP70 induction, respectively. RESULTS: PGA1 strongly reduced viral replication in Hep-2 cells, particularly when added during the early stages of viral replication. Although PGA1 treatment inhibited viral replication by 95% at 24 hours post-infection (hpi), viral structural protein synthesis was inhibited only by 15%. TEM analysis suggested that PGA1 inhibited replication before viral morphogenesis. Western blot and densitometry analyses showed that PGA1 treatment increased HSP70 protein levels, although this was not detectable via autoradiography. CONCLUSIONS: PGA1 inhibits MAYV replication in Hep-2 cells at early stages of viral replication, prior to production of viral structural proteins, possibly via HSP70 induction.


Subject(s)
Humans , Animals , Cattle , Prostaglandins A/pharmacology , Virus Replication/drug effects , Alphavirus/drug effects , HSP70 Heat-Shock Proteins/pharmacology , Epithelial Cells/virology , Antiviral Agents/pharmacology , Cell Line , Blotting, Western , Alphavirus/ultrastructure , Microscopy, Electron, Transmission , Electrophoresis, Polyacrylamide Gel , Epithelial Cells/ultrastructure
12.
Braz. j. infect. dis ; 22(3): 186-192, May-June 2018. tab, graf
Article in English | LILACS | ID: biblio-974205

ABSTRACT

ABSTRACT Background This study aimed to evaluate the clinical effectiveness in terms of sustained virological response and tolerability of available second generation direct-acting antivirals in Brazilian patients. Methods This was a retrospective observational study conducted in six centers in Southern Brazil. The sample comprised adult patients who were chronically infected with hepatitis C virus, regardless of virus genotype, fibrosis stage, or prior treatment. Statistical analysis was performed to compare the effectiveness among the treatments, and also to uncover the factors influencing the achievement of sustained virological response. Results A total of 296 patients were included in the study, with the majority receiving sofosbuvir with daclatasvir (59%) or sofosbuvir with simeprevir (26%). Overall sustained virological response rates were approximately 91.6%. For genotype 1, sofosbuvir with daclatasvir had an sustained virological response rate of approximately 95%, while the sustained virological response rate of sofosbuvir with simeprevir was 92%; this difference was statistically significant only for subtype 1b. The only treatment used for genotype 3 patients was sofosbuvir with daclatasvir, and lower rates of sustained virological response were observed for this group, compared to genotype 1 (84% versus 95%, p < 0.05). Apart from this difference between genotypes, and a difference between patients who achieved rapid virologic response compared with those who did not, there were no other statistically significant factors associated with sustained virological response. Conclusions The results point to the effectiveness of second-generation direct-acting antivirals in hepatitis C virus Brazilian patients, especially those with genotype 1. Furthermore, that patients with genotype 3 need more attention and adjustments in available treatment options.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Antiviral Agents/pharmacology , Hepatitis C, Chronic/drug therapy , Reference Values , Ribavirin/pharmacology , Time Factors , Brazil , Logistic Models , Polymerase Chain Reaction , Retrospective Studies , Viral Load , Hepatitis C, Chronic/complications , Dose-Response Relationship, Drug , Simeprevir/pharmacology , Sofosbuvir/pharmacology , Sustained Virologic Response , Imidazoles/pharmacology , Liver Cirrhosis/virology
13.
Arq. gastroenterol ; 55(2): 184-187, Apr.-June 2018. tab
Article in English | LILACS | ID: biblio-950515

ABSTRACT

ABSTRACT BACKGROUND: The interaction between serum lipids and C virus infection is well known, as are serum lipid levels in the Peg-IFN / RBV-based treatment. However, with direct action antivirals (DAAs) this behavior is still unclear. OBJECTIVE: To compare serum lipids levels between patients treated with Peg-IFN/RBV and DAAs and to evaluate lipids in sustained virological response (SVR) with DAAs. METHODS: Retro prospective study comparing the behavior of total cholesterol (TC), low-density lipoprotein (LDL) and triglycerides (TG) serum levels during treatment with DAAs (G-DAAs) and a control historic group Peg-IFN/RBV (G-PR). Coorte, prospective study, to study the behavior of lipids in the SVR with DAAs. Data were collected at the beginning of treatment (baseline: t-base) and at week 12 of treatment (t-12) for G-DAAs and at week 24 (t-24) for G-PR, groups. In the cohort evaluation, the samples at t-base and at week 12 after the end of treatment (t-SVR). Delta lipids: difference between lipids in t-12 / t-24 minus t-base for comparison between G-PR and G-AADs groups and t-SVR minus t-base for lipid analysis in SVR. Analysis with Kruskal Wallis and Wilcoxon tests to compare the delta lipids of the groups. The P value was 0.05. RESULTS: In the assessment between G-PR and G-DAAs groups, we included 63 and 121 patients, respectively. The groups did not differ one from the other (BMI, sex, genotype, fibrosis, total cholesterol, LDL, and TG) except by age (50.38±10.44 vs 56±9.69, P=0.0006). We observed a decrease in levels of TC and LDL and an increase in TG, in G-PR, and in G-DAAs the opposite (Δ TC -13.9±34.5 vs 4.12±34.3 P=0.0005, Δ LDL -7.16±32 vs 10.13±29.92, P=0.003, Δ TG 4.51±53.7 vs -8.24±49.93, P=0.0025). In the coorte analysis, we included 102 patients, 70% men and 56% F4, 95 of them reached SVR. We observed an increase of TC and LDL and a decrease of TG in both groups (SVR and non SVR), with no statistical difference (Δ TC P=0.68; Δ LDL P=0.69; Δ TG P=0.43). We did not find significant difference in delta evaluation by genotype 1 and 3 (Δ TC +29.7±40.2 vs +13.4±30.3, P=0.06; Δ LDL +21.4±28.6 vs +16.6±31.3, P=0.41; Δ TG -3.6±60.6 vs -0.7±40, P=0.91). CONCLUSION: Serum lipids level differed during treatment with Peg-IFN and DAAs. Treatment with DAAs was associated with an increase of TC and LDL and a decrease of TG, independently of SVR.


RESUMO CONTEXTO: A interação entre lípides séricos e infecção pelo vírus C já é bem conhecida, assim como o comportamento dos níveis séricos daqueles durante o tratamento com Peg-IFN/RBV. No entanto, com antivirais de ação direta (AADs) este comportamento ainda não está claro. OBJETIVO: Comparar os níveis séricos de lípides entre pacientes tratados com Peg-IFN/RBV e AADs e avaliar os lípides na resposta virológica sustentada (RVS) com AADs. MÉTODOS: Estudo retro prospectivo comparando o comportamento dos níveis séricos de colesterol total (CT), lipoproteínas de baixa densidade (LDL) e triglicérides (TG) durante o tratamento com AADs (G-AADs) e um grupo histórico de controle Peg-IFN/RBV (G-PR). Coorte, estudo prospectivo, para estudar o comportamento dos lípides na RVS com AADs. Os dados foram coletados no início do tratamento (baseline: t-base) e na décima segunda semana de tratamento (t-12) para G-AADs e na vigésima quarta semana de tratamento (t-24) para G-PR para a análise comparativa entre os dois grupos. Na avaliação de coorte, as amostras foram coletadas no t-base e na décima segunda semana após o término do tratamento (t-RVS). Delta lípides: diferença entre lípides em t-12/t-24 menos t-base para comparação entre os grupos G-PR e G-AADs e t-RVS menos t-base para análise de lípides na RVS. A análise estatística descritiva, os testes não paramétricos de Kruskal Wallis e Wilcoxon foram utilizados para comparar o delta lípides dos grupos. O valor de P considerado foi de 0,05. RESULTADOS: Na avaliação entre os grupos G-PR e G-AADs, incluímos 63 e 121 pacientes, respectivamente. Os grupos não diferiram um do outro (IMC, sexo, genótipo, fibrose, colesterol total, LDL e TG), exceto por idade (50,38±10,44 vs 56±9,69, P=0,0006). Observamos uma diminuição nos níveis de CT e LDL e um aumento de TG no G-PR, no G-AADs ocorreu o oposto (Δ CT -13,9±34,5 vs 4,12±34,3 P=0,0005, Δ LDL -7,16±32 vs 10,13±29,92, P=0,003, Δ TG 4,51±53,7 vs -8,24±49,93, P=0,0025). Na análise de coorte, foram incluídos 102 pacientes, 70% homens e 56% F4. Noventa e cinco deles atingiram a RVS. Observamos um aumento de CT e LDL e uma diminuição de TG em ambos os grupos (RVS e não RVS), sem diferença estatística (Δ CT P=0,68; Δ LDL P=0,69; Δ TG P=0,43). Não encontramos diferença significativa na avaliação dos deltas pelos genótipos 1 e 3 (Δ CT +29,7±40,2 vs +13,4±30,3, P=0,06; Δ LDL + 21,4±28,6 vs +16,6±31,3, P=0,41; Δ TG -3,6±60,6 vs -0,7±40, P=0,91). CONCLUSÃO: O nível de lípides séricos diferiu durante o tratamento com Peg-IFN/RBV e AADs. O tratamento com AADs foi associado a um aumento de CT e LDL e uma diminuição de TG, independentemente da RVS.


Subject(s)
Humans , Male , Female , Adult , Antiviral Agents/therapeutic use , Hepatitis C/drug therapy , Hepacivirus/genetics , Sustained Virologic Response , Lipids/blood , Antiviral Agents/pharmacology , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Triglycerides/blood , Recombinant Proteins/therapeutic use , Prospective Studies , Interferon-alpha/therapeutic use , Hepatitis C/virology , Hepacivirus/drug effects , Drug Therapy, Combination , Genotype , Cholesterol, LDL/blood , Middle Aged
14.
Rev. Soc. Bras. Med. Trop ; 51(2): 141-145, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-897064

ABSTRACT

Abstract INTRODUCTION: Human cytomegalovirus is one of the causes of opportunist infections in immunocompromised patients, and is triggered by factors such as state of viral latency, weakened immune responses, and development of antiviral resistance to ganciclovir, the only drug offered by the public health system in Brazil to treat the infection. The goal of this study was to identify mutations that may be associated with antiviral resistance in immunocompromised patients. METHODS: Molecular analysis was performed in 82 blood samples and subjected to genomic DNA extraction by a silica-based method. Three sequences of the HCMV UL97 gene, which encodes a phosphotransferase protein required for activation of ganciclovir, were amplified by polymerase chain reaction. Pyrosequencing methods were applied to one external 2096-bp segment DNA and two internal sequences between nucleotides 1087 to 1828 to detect mutations in this gene. RESULTS: Approximately 10% of sequences contained mutations between nucleotides 377 and 594, in conserved regions of the UL97 gene, leading to amino acid changes. Eleven coding mutations were identified, including changes leading to amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first time in Brazil. In addition, one mutation (A594V) that is associated with ganciclovir resistance was detected in a kidney transplant patient. CONCLUSIONS: Further studies to detect mutations associated with HCMV resistance to antiviral drugs are required to demonstrate the need to increase the variety and availability of drugs used to treat viral infections in the public health care system in Brazil.


Subject(s)
Humans , Antiviral Agents/therapeutic use , Phosphotransferases/genetics , Immunocompromised Host , Cytomegalovirus Infections/drug therapy , Cytomegalovirus/enzymology , Drug Resistance, Viral/genetics , Mutation/genetics , Antiviral Agents/pharmacology , Case-Control Studies , Polymerase Chain Reaction , Cross-Sectional Studies , Cytomegalovirus/drug effects , Cytomegalovirus/genetics , Drug Resistance, Viral/drug effects , Genotype
15.
Braz. J. Pharm. Sci. (Online) ; 54(spe): e01002, 2018. graf
Article in English | LILACS | ID: biblio-974426

ABSTRACT

Few Zika virus (ZIKV) outbreaks had been reported since its first detection in 1947, until the recent epidemics occurred in South America (2014/2015) and expeditiously became a global public health emergency. This arbovirus reached 0.5-1.3 million cases of ZIKV infection in Brazil in 2015 and rapidly spread in new geographic areas such as the Americas. Despite the mild symptoms of the Zika fever, the major concern is related to the related severe neurological disorders, especially microcephaly in newborns. Advances in ZIKV drug discovery have been made recently and constitute promising approaches to ZIKV treatment. In this review, we summarize current computational drug discovery efforts and their applicability to discovery of anti-ZIKV drugs. Lastly, we present successful examples of the use of computational approaches to ZIKV drug discovery.


Subject(s)
Computer-Aided Design/statistics & numerical data , Drug Discovery/instrumentation , Zika Virus , Antiviral Agents/pharmacology , Triage/methods , Computing Methodologies , Flavivirus
16.
An. acad. bras. ciênc ; 89(3): 1555-1564, July-Sept. 2017. tab, graf
Article in English | LILACS | ID: biblio-886762

ABSTRACT

ABSTRACT Diarrhea is an infectious disease caused by bacterial, virus, or protozoan, and dengue is caused by virus, included among the neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antidiarrheal potential of species of Maytenus genus, a phytochemical investigation followed by antibacterial activity test with extracts of branches and heartwood and bark of roots from Maytenus gonoclada were conducted. Moreover, due the frequency of isolation of lupeol from Maytenus genus the antiviral activity against Dengue virus and cytotoxicity of lupeol and its complex with β-cyclodextrins were also tested. The results indicated the bioactivity of ethyl acetate extract from branches and ethanol extract from heartwood of roots of M. gonoclada against diarrheagenic bacteria. The lupeol showed potent activity against Dengue virus and low cytotoxicity in LLC-MK2 cells, but its complex with β-cyclodextrin was inactive. Considering the importance of novel and selective antiviral drug candidates the results seem to be promising.


Subject(s)
Antiviral Agents/pharmacology , Plant Extracts/pharmacology , Maytenus/chemistry , Dengue Virus/drug effects , Pentacyclic Triterpenes/pharmacology , Anti-Bacterial Agents/pharmacology , Antidiarrheals/pharmacology , Antiviral Agents/isolation & purification , Cell Line , Maytenus/classification , Pentacyclic Triterpenes/isolation & purification , Anti-Bacterial Agents/isolation & purification , Antidiarrheals/isolation & purification
18.
Mem. Inst. Oswaldo Cruz ; 112(6): 458-468, June 2017. tab, graf
Article in English | LILACS | ID: biblio-841802

ABSTRACT

ABSTRACT BACKGROUND Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL) and bark (UGB) of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV) infection and in immunological parameters associated with in vivo physiopathological features. METHODS Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7) were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA) or flow cytometry. FINDINGS The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1), which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAIN CONCLUSIONS The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.


Subject(s)
Humans , Antiviral Agents/pharmacology , Plant Extracts/pharmacology , Cell Survival/drug effects , Cytokines/drug effects , Cytokines/immunology , Chemokines/drug effects , Chemokines/immunology , Uncaria/chemistry , Dengue/physiopathology , Dengue/immunology , Dengue/virology , Dengue Virus/drug effects , Dengue Virus/immunology , Antigens, Viral/drug effects , Antigens, Viral/immunology , Enzyme-Linked Immunosorbent Assay , Flow Cytometry
19.
Ann. hepatol ; 16(2): 215-220, Mar.-Apr. 2017. tab
Article in English | LILACS | ID: biblio-887225

ABSTRACT

ABSTRACT Introduction and aim. The effect of the new direct acting antiviral drugs (DAAs) for chronic hepatitis C (HCV) on glycemic control is unknown. Materials and methods. We conducted a retrospective cohort study of patients who were treated for chronic HCV with direct-acting antiviral medications at a single academic institution between May 2013 and April 2016. Univariate analysis was performed comparing subjects pre- and post-treatment. Results. One hundred seventy-five consecutive adult patients were treated for chronic HCV and met enrollment criteria. The majority (80.8%) were genotype 1 and overall cohort sustained virologic response at week 12 (SVR12) was 97.8%. Thirty-one (18.5%) had diabetes mellitus (DM); twenty-six had pre- and post-treatment HbA1c values. Of these, 76.9% were male and 61.5% had cirrhosis. Ninety-six percent were prescribed sofosbuvir-based therapy and all but one (96.8%) achieved SVR12. Three patients were started on treatment despite meeting the definition for poorly controlled DM (HbA1c > 9 mg/dL). There was no significant difference when comparing pre-treatment (7.36 mg/dL, 95% CI 6.55-8.16) to post-treatment HbA1c (7.11 mg/dL, 95% CI 6.34-7.88, p = 0.268). Thirty-one percent of subjects required dose escalation or the initiation of insulin based therapy during treatment. Discussion. Although chronic HCV is associated with exacerbation of insulin resistance, our results showed HbA1c to be unaffected by eradication of chronic HCV with DAA in diabetic patients with and without cirrhosis. Paradoxically, almost 1/3 of patients required escalation of anti-diabetic therapy during treatment. Long-term studies are warranted to understand the relationship between HCV viral eradication and insulin metabolism.(AU)


Subject(s)
Humans , Antiviral Agents/pharmacology , Hepatitis C, Chronic/drug therapy , Glycemic Index , Retrospective Studies , Cohort Studies , Diabetes Mellitus/pathology , Insulin/metabolism
20.
Braz. j. med. biol. res ; 50(10): e6586, 2017. tab, graf
Article in English | LILACS | ID: biblio-888930

ABSTRACT

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.


Subject(s)
Humans , Antiviral Agents/pharmacology , Enterovirus A, Human/drug effects , Naphthoquinones/pharmacology , Rhabdomyosarcoma/virology , Blotting, Western , Cell Line, Tumor , Cytokines/analysis , Dose-Response Relationship, Drug , Real-Time Polymerase Chain Reaction , Toxicity Tests , Viral Plaque Assay , Virus Replication/drug effects
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