Current and Future Therapies for Hepatitis C Virus Infection

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1800,USA.
New England Journal of Medicine (Impact Factor: 55.87). 05/2013; 368(20):1907-17. DOI: 10.1056/NEJMra1213651
Source: PubMed
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    • "Still, generation of novel mAbs is a relevant issue, even though antiviral drugs, such as boceprevir and telaprevir, are currently in clinical use. However, besides their toxic side effects, their use may be limited by the occurrence of drug-resistant phenotypes [12] [13] [14] [15] [16]. Furthermore, these antiviral drugs are not as effective to prevent graft reinfection in patients subjected to liver transplantation, since "
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    ABSTRACT: Expanding the availability of monoclonal antibodies interfering with hepatitis C virus infection of hepatocytes is an active field of investigation within medical biotechnologies, to prevent graft reinfection in patients subjected to liver transplantation and to overcome resistances elicited by novel antiviral drugs. In this paper, we describe a complete pipeline for screening of phage display libraries of human scFvs against native Claudin-1, a tight-junction protein involved in hepatitis C virus infection, expressed on the cell surface of human hepatocytes. To this aim, we implemented a high-throughput sequencing approach for library screening, followed by a simple and effective strategy to recover active binder clones from enriched sublibraries. The recovered clones were successfully converted to active immunoglobulins, thus demonstrating the effectiveness of the whole procedure. This novel approach can guarantee rapid and cheap isolation of antibodies for virtually any native antigen involved in human diseases, for therapeutic and/or diagnostic applications.
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    • "One of the most relevant biotechnological applications of these new semisynthetic lipases was in the regioselective deprotection of per-Oacetylated carbohydrates and nucleosides (Romero et al., 2012) (Fig. 2). Carbohydrates and nucleosides analogues have attracted intense interest in medicine, where they are used as antitumor and antiviral agents (Calvaresia and Hergenrother, 2013; Liang and Ghany, 2013). Several nucleoside analog reverse-transcriptase inhibitors have been licensed and used in treatment of HIV/AIDS, for example Zidovudine (Esté and Cihlar, 2010). "
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    ABSTRACT: The development of new and successful biotransformation processes of key interest in medicinal and pharmaceutical chemistry involves creating new biocatalysts with improved or even new activities and selectivities. This review emphasizes the new emerging developed strategies to achieve this goal, site-selective chemical modification of enzymes using tailor-made peptides, specific insertion of metals or organometallic complexes into proteins producing bio-catalysts with multiple activities and computational design for creating evolved artificial enzymes with non-natural synthetic catalytic activities. Copyright © 2014. Published by Elsevier Inc.
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    • "DAAs have achieved high response rates with cure in late-stage clinical trials, but high costs will limit their broad access. In addition, certain patient groups (e.g., genotype 3, renal failure, hepatic decompensation, and liver transplantation) will need complementary approaches (Chung and Baumert, 2014; Liang and Ghany, 2013). "
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    ABSTRACT: Fighting viral infections is hampered by the scarcity of viral targets and their variability, resulting in devel-opment of resistance. Viruses depend on cellular molecules—which are attractive alternative tar-gets—for their life cycle, provided that they are dispensable for normal cell functions. Using the model organism Drosophila melanogaster, we iden-tify the ribosomal protein RACK1 as a cellular factor required for infection by internal ribosome entry site (IRES)-containing viruses. We further show that RACK1 is an essential determinant for hepatitis C virus translation and infection, indicating that its function is conserved for distantly related human and fly viruses. Inhibition of RACK1 does not affect Drosophila or human cell viability and proliferation, and RACK1-silenced adult flies are viable, indicating that this protein is not essential for general transla-tion. Our findings demonstrate a specific function for RACK1 in selective mRNA translation and un-cover a target for the development of broad antiviral intervention. INTRODUCTION
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