Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an

RNA-dependent RNA polymerase RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to t ...

, having the key function of replicating HCV's viral

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

by using the viral positive RNA strand as a template to catalyze the

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer, monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are ...

of ribonucleoside triphosphates (rNTP) during

RNA replication RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to t ...

. 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 An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA (ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruses ...

replication and thus treat or cure HCV. They are often used in combination with NS5A inhibitors. * Beclabuvir, currently in

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s. *

Dasabuvir Dasabuvir, sold under the brand name Exviera, is an antiviral medication for the treatment of hepatitis C. It is often used together with the combination medication ombitasvir/paritaprevir/ritonavir specifically for hepatitis C virus (HCV) type 1 ...

(Viekira Pak), non-nucleoside/nucleotide analog, approved by

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

in December 2014 (only in combination with ombitasvir,

paritaprevir Paritaprevir (previously known as ABT-450) is an acylsulfonamide inhibitor of the NS3- 4A serine protease manufactured by Abbott Laboratories that shows promising results as a treatment of hepatitis C. When given in combination with ritonavir an ...

, and ritonavir). * Deleobuvir, development terminated. * Filibuvir, development terminated. * Radalbuvir, currently in clinical trials. * Setrobuvir, development terminated. *

Sofosbuvir Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken Oral administration, by mouth. Common side effects include fatigue, headache, nausea, and trouble sleeping. Side effects are gen ...

(Sovaldi; Harvoni (combination with ledipasvir)): nucleotide analog, approved by the FDA in December 2013.

References

{{Viral proteins Viral nonstructural proteins Hepatitis C virus