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Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA-dependent RNA polymerase, having the key function of replicating HCV's viral RNA by using the viral positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication. Several crystal structures of NS5B polymerase in several crystalline forms have been determined based on the same consensus sequence BK (HCV-BK, genotype 1). The structure can be represented by a right hand shape with fingers, palm, and thumb. The encircled active site, unique to NS5B, is contained within the palm structure of the protein. Recent studies on NS5B protein genotype 1b strain J4's (HC-J4) structure indicate a presence of an active site where possible control of nucleotide binding occurs and initiation of de-novo RNA synthesis. De-novo adds necessary primers for initiation of RNA replication.
Drugs targeting NS5B
Several drugs are either on the market or in various stages of research target NS5B as a means to prevent further viral RNA replication and thus treat or cure HCV. They are often used in combination with NS5A inhibitors.
O'Farrell D, Trowbridge R, Rowlands D, Jäger J (February 2003). "Substrate complexes of hepatitis C virus RNA polymerase (HC-J4): structural evidence for nucleotide import and de-novo initiation". Journal of Molecular Biology. 326 (4): 1025–35. doi:10.1016/s0022-2836(02)01439-0. PMID12589751.
Biswal BK, Wang M, Cherney MM, Chan L, Yannopoulos CG, Bilimoria D, et al. (August 2006). "Non-nucleoside inhibitors binding to hepatitis C virus NS5B polymerase reveal a novel mechanism of inhibition". Journal of Molecular Biology. 361 (1): 33–45. doi:10.1016/j.jmb.2006.05.074. PMID16828488.
