Narrow Therapeutic Window of Ribavirin as an Inhibitor of Nitric Oxide Synthesis is Broadened by Macromolecular Prodrugs

• Published in: Biomacromolecules Vol. 14; no. 11; pp. 3916 - 3926
• Main Authors: Wohl, Benjamin M, Smith, Anton A. A, Kryger, Mille B. L, Zelikin, Alexander N
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 11.11.2013
• Subjects: adverse effects; Animals; anti-inflammatory activity; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Applied sciences; Biological and medical sciences; Cell Survival - drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Drug Design; drug therapy; drugs; Exact sciences and technology; Hep G2 Cells; Hepatitis C virus; Humans; inhibitory concentration 50; Macromolecular Substances - chemical synthesis; Macromolecular Substances - chemistry; Macromolecular Substances - pharmacology; macrophages; Macrophages - drug effects; Macrophages - metabolism; mechanism of action; median effective concentration; Medical sciences; Mice; Molecular Structure; molecular weight; nitric oxide; Nitric Oxide - biosynthesis; Organic polymers; pharmacokinetics; Pharmacology. Drug treatments; Physicochemistry of polymers; polymerization; polymers; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; Prodrugs - chemical synthesis; Prodrugs - chemistry; Prodrugs - pharmacology; pyrrolidones; Ribavirin - chemistry; Ribavirin - pharmacology; Structure-Activity Relationship; Time Factors; Biological properties; Triazole derivative copolymer; Control release polymer; Antiinflammatory agent; Red blood cell; Cytotoxicity; Drug carrier; Prodrug; Experimental study; Biological activity; Ribavirin; Monodispersed polymer; Chain transfer; Hepatocyte; Activity concentration relation; Nitric oxide; Preparation; Pyrrolidone(vinyl) copolymer; Antiviral; Acrylate copolymer; Radical copolymerization

Ribavirin (RBV), a broad-spectrum antiviral agent, is a standard medication against hepatitis C virus (HCV). However, despite the decades of clinical success, the mechanism of action of this drug against HCV remains a subject of debate. Furthermore, the appeal of this therapeutic agent is considerab...