Hepatitis C virus (HCV) is a significant global health concern, responsible for chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The virus has a single-stranded positive-sense RNA genome that encodes a polyprotein, which is processed into structural and nonstructural proteins. Among these, the nonstructural protein 5A (NS5A) plays a crucial role in the virus’s life cycle and pathogenesis .
HCV is classified into several genotypes, with genotype 3a being one of the most prevalent worldwide. Genotype-3a is particularly significant due to its association with a higher risk of liver steatosis and a faster progression to cirrhosis compared to other genotypes . The genetic diversity of NS5A in genotype-3a has been implicated in resistance to interferon-based therapies, making it a critical target for antiviral drug development .
Recombinant NS5A proteins are produced using various expression systems to study their structure, function, and interactions with host cellular factors. These recombinant proteins are valuable tools for understanding the molecular mechanisms of HCV replication and pathogenesis. They are also used in the development of diagnostic assays and therapeutic interventions .
Research on NS5A has led to the development of direct-acting antivirals (DAAs) that target this protein, significantly improving the treatment outcomes for HCV-infected patients. However, the emergence of resistance-associated substitutions (RASs) in NS5A poses a challenge to the efficacy of these therapies . Continuous research is essential to identify new inhibitors and develop strategies to overcome resistance.