Dasabuvir is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents, Ombitasvir, Paritaprevir, and Ritonavir. Hepatitis C virus lipoviroparticles enter target hepatocytes via receptor-mediated endocytosis. 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. The genome polyprotein is cleaved by host and viral proteases into 10 viral proteins. The nucleocapsid protein core and the two envelope proteins E1 and E2 form the N terminus of the polyprotein and are the structural components of HCV virions. The precursor also gives rise to the viroporin p7 and six non-structural (NS) proteins. Dasabuvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5B, which is an RNA-dependent RNA polymerase. RNA polymerase is required for viral RNA replication and assembly of HCV virions. By binding to nonstructural protein 5B outside of the active site of the enzyme, dasabuvir induces a conformational change. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B. For full viral replication and maturation, nonstructural protein 5B is required so viral RNA replication cannot occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.

Dasabuvir Pathway References