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Pathway Description
Elbasvir Action Pathway
Homo sapiens
Drug Action Pathway
Elbasvir is a direct-acting antiviral medication used as part of combination therapy to treat chronic hepatitis C Elbasvir, when used in combination with grazoprevir as the combination product Zepatier, is indicated for use with or without ribavirin for the treatment of chronic HCV genotypes 1 or 4 infection in adults.7
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
Elbasvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5A, which is required for viral RNA replication and assembly of HCV virions. The exact mechanism of this protein is unknown. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B. For full viral replication and maturation, replication complexes need to be in close proximity to lipid droplets, which requires the protein nonstructural protein 5A. Without the lipid droplet due to inhibition of nonstructural protein 5A, full viral RNA replication is unable to occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.
References
Elbasvir Pathway References
Herker E, Ott M: Unique ties between hepatitis C virus replication and intracellular lipids. Trends Endocrinol Metab. 2011 Jun;22(6):241-8. doi: 10.1016/j.tem.2011.03.004. Epub 2011 Apr 15.
Pubmed: 21497514
Bell AM, Wagner JL, Barber KE, Stover KR: Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C. Int J Hepatol. 2016;2016:3852126. doi: 10.1155/2016/3852126. Epub 2016 Jun 15.
Pubmed: 27403342
Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 Jul;77(10):1043-1055. doi: 10.1007/s40265-017-0753-x.
Pubmed: 28497432
Balasubramaniam M, Reis RS: Computational Target-Based Drug Repurposing of Elbasvir, an Antiviral Drug Predicted to Bind Multiple SARS-CoV-2 Proteins ChemRxiv.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208261s002lbl.pdf
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