Victrelis (boceprevir)

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Contents 1 Hepatitis C Virus 2 Victrelis 3 Mechanism of Action 4 References

Hepatitis C Virus

The Hepatitis C virus (HCV) is a blood-borne, single stranded RNA virus. ^[1] Chronic Hepatitis C infection is a leading cause of mortality and morbidity across the globe, affecting almost 170 million people. ^[2] The genome of HCV encodes a polyprotein precursor of approximately 3,000 amino acids, which are cleaved into 10 proteins by various proteases, one of which is the non-structural protein 3 (NS3) serine protease.^[3]

spinqualitylabelsall models Structure of Hepatitis C Viral NS3 protease domain complexed with NS4A peptide and ketoamide SCH503034 (PDB code 2oc8) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Victrelis

Victrelis (boceprevir) is an antiviral Hepatitis C medication approved by the United States Food and Drug Administration in 2011. Victrelis is an inhibitor of the NS3 serine protease.^[4] Inhibition of this protease prevents viral replication in Hepatitis C virus infected cells.^[4]

Mechanism of Action

Victrelis is a protease inhibitor. A protease is an enzyme that cleaves large polypeptides to create fragments that are small enough to be sequenced for effective replication^[5] Victrelis specifically inhibits the HCV NS3/4A protease, which is responsible for cleavage at four different sites along the polyprotein: NS3/NS4A, NS4A/NS4B, NS4B/NS5A, and NS5A/NS5B.^[3] In previous experiements, when any member of the catalytic triat was replaced by a different residue, cleavage at the NS3/NS4A, NS4A/NS4B, NS4B/NS5A, and NS5A/NS5B locations was inhibited.^[3] Mammals also utilize serine proteases to cleave lengthy polypeptides.^[5]

References

1. ↑ Centers for Disease Control and Prevention. (2015). Viral hepatitis - hepatitis C information. Retrieved from http://www.cdc.gov/hepatitis/hcv/index.htm
2. ↑ doi: https://dx.doi.org/10.1177/1756383X11436317
3. ↑ ^{3.0 3.1 3.2} Lin C. HCV NS3-4A Serine Protease PMID:21250386
4. ↑ ^{4.0 4.1} Merck & Co., Inc. (n.d.) Highlights of prescribing information. Retrieved from https://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf
5. ↑ ^{5.0 5.1} Voet, D., Voet, J., Pratt, C. (2013). Fundamentals of biochemistry: life at the molecular level (4th ed.). Hoboken, New Jersey: John Wiley & Sons, Inc.

^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}