Hepatitis C therapy with HCV NS5B polymerase inhibitors.

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Soriano V, Vispo E, de Mendoza C, Labarga P, Fernandez-Montero JV, Poveda E, Trevino A, Barreiro P

Hepatitis C therapy with HCV NS5B polymerase inhibitors.

Expert Opin Pharmacother. 2013 Jun;14(9):1161-70. doi: 10.1517/14656566.2013.795543. Epub 2013 Apr 27.

PubMed ID

23621117 [ View in PubMed

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Abstract

INTRODUCTION: Several HCV polymerase inhibitors are in advanced stages of clinical development. They are nucleos(t)ide and non-nucleoside analogs. Nucleos(t)ides inhibit viral replication acting as chain terminators whereas non-nucleosides block allosterically the HCV polymerase. Sofosbuvir is an uridine analog and currently the most promising HCV polymerase inhibitor, being active across all HCV genotypes. It has good tolerability and a robust barrier to resistance. In contrast, non-nucleoside analogs have low to moderate antiviral potency, a low barrier to resistance and inhibit only HCV genotype 1. AREAS COVERED: Studies conducted with distinct HCV polymerase inhibitors as part of interferon-free combinations have opened a new landscape in which shorter treatment duration and all-oral regimens are envisioned as the future curative treatment for most chronic hepatitis C patients. EXPERT OPINION: Antiviral drug development for HCV is progressing at a feverish pace. Amongst HCV polymerase inhibitors, sofosbuvir has positioned as unique companion with ribavirin as therapy for most HCV genotypes 2 or 3, and along with NS5A inhibitors for other HCV genotypes. Non-nucleoside HCV polymerase inhibitors are being developed only as part of all-oral combinations with protease inhibitors. The expected high cost of DAAs will preclude their prompt and wider use, allowing room for using alternative cheaper options in easier-to-treat patient populations.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Dasabuvir	Nonstructural protein 5B (NS5B)	Protein		Yes	Inhibitor	Details