ABSTRACT
La hepatitis por virus C constituye un problema de salud importante en México. El diagnóstico de poblaciones de alto riesgo es esencial dada la probabilidad de desarrollar enfermedad crónica, cirrosis, descompensación de la cirrosis y la consecuente necesidad de un trasplante hepático o de desarrollar carcinoma hepatocelular. Actualmente, el tratamiento de elección establecido (TEE) incluye interferón pegilado y ribavirina, los cuales han mostrado una tasa de respuesta de alrededor de 57 por ciento en el caso del genotipo 1, el más prevalente en México. Sabemos que entre 30 y 60 por ciento de la población no muestra una respuesta viral sostenida (RVS) o curación. Por lo tanto, en este artículo se revisan las estrategias terapéuticas existentes para optimizar el tratamiento, y se describen también las estrategias de tratamiento para el futuro. Eventualmente, será posible adicionar una o dos moléculas de los nuevos antivirales que actúan directamente (AAD) sobre áreas específicas del virus al TEE. Cada una de ellas cuenta con mecanismo de acción diferente y se está contemplando la posibilidad de una terapéutica libre de interferón después del año 2015.
Infection by hepatitis C virus constitutes an important health problem in Mexico. Diagnosis of high-risk population is essential given the probability of developing chronic disease, cirrhosis and cirrhosis decompensation, likely leading to the need of a liver transplant and/or the development of hepatocellular carcinoma. Currently, the standard of care (SOC) treatment includes pegylated interferon and ribavirin, which have shown an approximately 57 percent rate response in genotype 1, the most prevalent in Mexico. It is known that between 30 and 60 percent of the infected population does not show a sustained virological response or cure. Therefore, in this article, we review existing therapeutic strategies in order to optimize the treatment. Future treatment strategies are also described. Eventually, it will be possible to add one or two molecules of the new directly acting antiviral drugs, to the SOC treatment. Each of them has a different action mechanism, and we are envisioning the possibility of an interferon-free therapy after 2015.
Subject(s)
Humans , Antiviral Agents/therapeutic use , Hepatitis C/drug therapy , Antiviral Agents/classification , Antiviral Agents/pharmacology , Drug Design , Drug Therapy, Combination , Forecasting , Genetic Predisposition to Disease , Genotype , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C/surgery , Host-Pathogen Interactions , Precision Medicine , Interferons/adverse effects , Interferons/classification , Interferons/therapeutic use , Medication Adherence , Molecular Targeted Therapy , Polymorphism, Single Nucleotide , Standard of Care , Viral Proteins/antagonists & inhibitorsABSTRACT
Prostaglandin Al (PGA1) inhibits Mayaro virus replication in Aedes albopictus cells at nontoxic doses to uninfected cells . At 10 ug/ml, PGA1 decreases virus production by 90 (per cent). The presence of PGA1 during virus adsorption, with no treatment after infection, reduces virus yield by 41 (per cent). Antiviral activity is observed even when treatment starts at one or two hours post-infection. However, in cells pre-treated with PGA1 during 24 hours, virus replication is not impaired. Thus, events ocurring during initial stages of infection and after virus adsorption and penetration must be the target of PGA1 action. SDS-PAGE analysis of 35S-methionine labelled proteins shows that PGA1 inhibits the synthesis of viral proteins and induces the synthesis of polypeptides with molecular weight of 70 kDa, 57 kDa and 23 kDa. In cells pre-treated with actinomycin D the induction of those proteins is suppressed. In addition, actinomycin D treatment prevents PGA1 antiviral activity, indicating that PGA1-induced stress proteins are probably involved in this mechanism
Subject(s)
Prostaglandins A/pharmacology , Aedes/cytology , Viral Proteins/antagonists & inhibitors , Virus Replication , Heat-Shock ProteinsABSTRACT
We have previously observed that interferon(recIFNa2b) blocks the process of mophogenesis of Mayaro virus in TC7 cells (monkey kidney). In this work we show that IFNa inhibits preferentially virus glycoproteins and their precursors, and this effects is probably correlated to the alterations in the morphogenesis process previously observed