Hepatitis C Virus (HCV) is a significant global health concern, affecting millions of people worldwide. It is a positive-sense single-stranded RNA virus that primarily targets the liver, leading to chronic liver diseases such as cirrhosis and hepatocellular carcinoma. The HCV genome encodes a single polyprotein, which is processed into structural and nonstructural proteins. Among these, the nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase crucial for viral replication.
NS5B is responsible for replicating the viral RNA by using the positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication . This unique function makes NS5B an attractive target for antiviral drug development. Several crystal structures of NS5B polymerase have been determined, providing insights into its mechanism of action and aiding in the design of inhibitors .
Recombinant NS5B refers to the NS5B protein expressed in a heterologous system, such as bacteria or yeast, for research and therapeutic purposes. The recombinant form allows for detailed biochemical and structural studies, which are essential for understanding the enzyme’s function and developing specific inhibitors . The expression and initial biochemical characterization of recombinant NS5B polymerase have been described, highlighting its potential as a therapeutic target .
NS5B is a critical component in the life cycle of HCV, and its inhibition can effectively halt viral replication. The development of direct-acting antivirals (DAAs) targeting NS5B has revolutionized HCV treatment, offering high cure rates with fewer side effects compared to previous therapies . The study of recombinant NS5B has been instrumental in identifying and optimizing these inhibitors, making it a cornerstone of HCV research.