ABSTRACT
Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-α, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids from Pterogyne nitens on the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids 1 and 2 inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid 2 block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid 1 activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of 1 and 2 possessing in vitro anti-HCV activity.
Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Fabaceae/chemistry , Flavonoids/chemistry , Flavonoids/pharmacology , Hepacivirus/drug effects , Flavones/chemistry , Flavones/pharmacology , Interferon-alpha/pharmacology , Virus Replication/drug effectsABSTRACT
Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. CX reduced virus entry and release but not replication. By treating cells with CP, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle.
Subject(s)
Antiviral Agents/isolation & purification , Crotalid Venoms/chemistry , Hepacivirus/drug effects , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cell Line , Crotalus , Crotoxin/chemistry , Crotoxin/pharmacology , Crystallography, X-Ray , Hepacivirus/physiology , Humans , Membrane Fusion/drug effects , Molecular Structure , Phospholipases A2/chemistry , Phospholipases A2/pharmacology , Virus Replication/drug effectsABSTRACT
PURPOSE: The use of patient-reported outcome questionnaires is recommended in orthopedic studies. However, validated tools are necessary to ensure the comparability of results across different studies, centers, and countries. The Brief Michigan Hand Questionnaire (BMHQ) can be used for outcome measures in self-evaluation after carpal tunnel release. This study aimed to translate the BMHQ to Portuguese to permit cross-cultural adaptation to Brazilians patients. METHODS: We translated the Brief Michigan Hand Questionnaire from the original version (English) to Brazilian Portuguese. The translation and cultural adaptation of the content of this tool consisted of six stages, according to the methodology proposed by medical literature: (1) initial translation of the questionnaire by two independent translators; (2) synthesis of translations and reconciliation; (3) back-translation to English of the reconciled version; (4) verification of the cultural equivalence process by an expert committee; (5) pre-testing in a sample of patients to verify understanding of the items; and (6) development of a final version of the BMHQ. RESULTS: The pre-final version of the tool was applied to 43 patients to verify its understanding. Pre-testing showed that the questions and options were satisfactorily understood. The number of items from the original English version was maintained in the Brazilian Portuguese version of BMHQ. DISCUSSION: The Brazilian Portuguese version of the BMHQ is easily understood by patients and will be useful to clinicians and researchers.