Asunaprevir, also known as BMS-650032, is an NS3 protease inhibitor used to treat hepatitis C genotype 1b. It as been found to be highly effective in dual-combination regimens with daclatasvir in patients with chronic HCV genotype 1b. The lipoviroparticles attach to LDL-R and SR-B1, and then the virus binds to CD81 and subsequently claudin-1 and occludin, which mediate the late steps of viral entry. The virus is internalized by clathrin-dependent endocytosis. RNA is released from the mature Hepatitis C virion and translated at the rough endoplasmic reticulum into a single Genome polyprotein. Asunaprevir accumulates in the liver after uptake into hepatocytes via solute carrier organic anion transporter family member 1B1. Asunaprevir inhibits NS3 protease, which is an enzyme that cleaves the heptatitis C virus polyprotein downstream of the NS3 proteolytic site, which generates nonstructural proteins NS3, NS4A, NS4B, NS5A, and NS5B. These proteins are required in viral RNA replication, therefore because of the inhibition of their formation, RNA replication cannot occur. Because RNA replication does not occur, the mature virion is unable to form. At higher concentration above their antiviral half-maximal effective concentration (EC50), NS3 protease cleaves two essential adaptor proteins that initiate signaling leading to activation of IFN regulatory factor 3 and IFN-α/β synthesis, which are mitochondrial antiviral-signaling proteins.

Asunaprevir Pathway References