Hepatitis C virus genomic RNA internal ribosome entry site (IRES) site 3 (HCV IRES site 3)

Hepatitis C virus (HCV) genomic RNA site 3 refers to a specific, highly conserved structural region within the internal ribosome entry site (IRES), primarily located in subdomain IIa. This site is critical for the cap-independent translation of the viral polyprotein, as it facilitates the proper positioning and recruitment of the host cell's 40S ribosomal subunit to the viral start codon. Because the IRES structure is essential for viral replication and is highly conserved across different HCV genotypes, it has been identified as a promising target for antiviral therapy. Small molecules, such as certain benzimidazole derivatives, have been designed to bind specifically to site 3, inducing a conformational change that locks the RNA in an inactive state and halts viral protein synthesis. While direct-acting antivirals (DAAs) targeting viral enzymes like NS3/4A or NS5B are currently the standard of care, targeting the HCV RNA site 3 offers a distinct mechanism of action that could potentially overcome resistance to existing therapies.

Other names

HCV IRES subdomain IIaHCV RNA site 3Hepatitis C virus internal ribosome entry site site 3HCV IRES benzimidazole binding site

Small molecules bind to the highly conserved subdomain IIa (site 3) of the HCV IRES, inducing a conformational change that prevents the recruitment of the 40S ribosomal subunit, thereby inhibiting viral protein synthesis.