Nonstructural protein 5B (NS5B) is a

viral protein A viral protein is both a component and a product of a virus. Viral proteins are grouped according to their functions, and groups of viral proteins include structural proteins, nonstructural proteins, regulatory proteins, and accessory proteins. Vi ...

found in the

hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...

(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 Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

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 ...

ribonucleoside triphosphates A ribonucleoside is a type of nucleoside including ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ...

(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 replication and thus treat or cure HCV. They are often used in combination with

NS5A Nonstructural protein 5A (NS5A) is a zinc-binding and proline-rich hydrophilic phosphoprotein that plays a key role in Hepatitis C virus RNA replication. It appears to be a dimeric form without ''trans''-membrane helices. Structure NS5A is deriv ...

inhibitors. *

Beclabuvir Beclabuvir (also known by the research name BMS-791325; abbreviated BCV) is an antiviral drug for the treatment of hepatitis C virus (HCV) infection that has been studied in clinical trials. In February 2017, Bristol-Myers Squibb began sponsoring ...

, 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 Ombitasvir is an antiviral drug for the treatment of hepatitis C virus (HCV) infection by AbbVie. In the United States, it is approved by the Food and Drug Administration for use in combination with paritaprevir, ritonavir and dasabuvir in the p ...

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 Ritonavir, sold under the brand name Norvir, is an antiretroviral drug used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor a ...

). *

Deleobuvir Deleobuvir (formerly BI 207127) was an experimental drug for the treatment of hepatitis C. It was being developed by Boehringer Ingelheim. It is a non-nucleoside hepatitis C virus NS5B polymerase inhibitor. Deleobuvir was tested in combinatio ...

, development terminated. *

Filibuvir Filibuvir (also known as PF-00868554, PF-868554) was a non-nucleoside orally available NS5B inhibitor developed by Pfizer for the treatment of hepatitis C. It binds to the non-catalytic Thumb II allosteric pocket of NS5B viral polymerase and cause ...

, development terminated. *

Radalbuvir Radalbuvir (INN, also known as GS-9669) is an experimental antiviral drug for the treatment of hepatitis C virus (HCV) infection developed by Gilead Sciences. Radalbuvir acts as an NS5B Nonstructural protein 5B (NS5B) is a viral protein found in ...

, currently in clinical trials. *

Setrobuvir Setrobuvir (also known as ANA-598) was an experimental drug candidate for the treatment of hepatitis C that was discovered at Anadys Pharmaceuticals, which was acquired by Roche in 2011; Roche terminated development in July 2015. It was in Phas ...

, 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 Ledipasvir/sofosbuvir, sold under the trade name Harvoni among others, is a medication used to treat hepatitis C. It is a fixed-dose combination of ledipasvir and sofosbuvir. Cure rates are 94% to 99% in people infected with hepatitis C virus (H ...

(combination with

ledipasvir Ledipasvir is a drug for the treatment of hepatitis C that was developed by Gilead Sciences. After completing Phase III clinical trials, on February 10, 2014, Gilead filed for U.S. approval of a ledipasvir/sofosbuvir fixed-dose combination table ...

)): nucleotide analog, approved by the FDA in December 2013.

References

{{Viral proteins Viral nonstructural proteins Hepatitis C virus