Titlebook: HCV: The Journey from Discovery to a Cure; Volume I Michael J. Sofia Book 2019 Springer Nature Switzerland AG 2019 HCV genome.Molecular Vir

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The Role of Interferon for the Treatment of Chronic Hepatitis C Virus Infectionkines that are an essential part of the body’s natural response to viral pathogens. In 1991, interferon-α (IFN-α) injections were first approved by the Food and Drug Administration for the treatment of HCV infection and remained the backbone of therapy until late 2014. As monotherapy, IFN-α injected

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Evolution of HCV NS5B Nucleoside and Nucleotide Inhibitorsive anti-HCV activity in a cell-based HCV replicon assay and, as their triphosphates, inhibited HCV NS5B polymerase enzyme in a cell-free assay. Since then, a number of new 2′-modified nucleoside analogs and nucleotide derivatives were synthesized and evaluated for direct inhibition of HCV replicati

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Discovery of Beclabuvir: A Potent Allosteric Inhibitor of the Hepatitis C Virus Polymeraseass of indolobenzazepines. Within this research, a strategic decision to abandon a highly potent but physiochemically problematic series in favor of one of lower molecular weight and potency was key in the realization of the program’s objectives. Subsequent cycles of analog design incorporating prog

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Evolution of HCV NS3/4a Protease Inhibitorsting point for medicinal chemistry. However, their less-than-ideal properties as leads would make the path to orally bioavailable inhibitors a highly challenging one. Extensive optimization efforts by multiple groups led to inhibitors with reduced peptidic character in both reversible and slowly rev

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Development and Marketing of INCIVEK (Telaprevir; VX-950): A First-Generation HCV Protease Inhibitor and ribavirin (R) which was associated with a low success rate in patients with the most common genotype 1 hepatitis C virus (HCV) infection (40–50%), significant treatment-limiting side effects, and a long (48-week) duration of treatment. The HCV protease inhibitor telaprevir (VX-950) was discover

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Discovery of Boceprevir, a Ketoamide-Derived HCV NS3 Protease Inhibitor, for Treatment of Genotype 1iviral agents, the only treatment option was a regimen of interferon and ribavirin. It was modestly effective with only ~40% of genotype 1 patients demonstrating sustained virologic response. It was also accompanied with severe side effects with flu-like symptoms and increased suicidal tendencies du

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