Targeting the NS5A protein of HCV: An emerging option

D. G. Cordek, J. T. Bechtel, A. T. Maynard, W. M. Kazmierski, Craig E. Cameron

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) infects more than 3% of the world's population, leading to an increased risk of cirrhosis and hepatocellular carcinoma. The current standard of care, a combination of pegylated interferon alfa and ribavirin, is poorly tolerated and often ineffective against the most prevalent genotype of the virus, genotype 1. The very recent approval of boceprevir and telaprevir, two HCV protease inhibitors, promises to significantly improve treatment options and outcomes. In addition to the viral protease NS3 and the viral polymerase NS5B, direct-acting antivirals are now in development against NS5A. A multifunctional phosphoprotein, NS5A is essential to HCV genome replication, but has no known enzymatic function. Here we report how the design of small-molecule inhibitors against NS5A has evolved from promising monomers to highly potent dimeric compounds effective against many HCV genotypes. We also highlight recent clinical data and how the inhibitors may bind to NS5A, itself capable of forming dimers.

Original languageEnglish (US)
Pages (from-to)691-711
Number of pages21
JournalDrugs of the Future
Volume36
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Protein C
Hepacivirus
Genotype
Ribavirin
Phosphoproteins
Standard of Care
Virus Replication
Protease Inhibitors
Interferon-alpha
Antiviral Agents
Hepatocellular Carcinoma
Fibrosis
Peptide Hydrolases
Genome
Viruses
Population

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Cordek, D. G., Bechtel, J. T., Maynard, A. T., Kazmierski, W. M., & Cameron, C. E. (2011). Targeting the NS5A protein of HCV: An emerging option. Drugs of the Future, 36(9), 691-711. https://doi.org/10.1358/dof.2011.036.09.1641618
Cordek, D. G. ; Bechtel, J. T. ; Maynard, A. T. ; Kazmierski, W. M. ; Cameron, Craig E. / Targeting the NS5A protein of HCV : An emerging option. In: Drugs of the Future. 2011 ; Vol. 36, No. 9. pp. 691-711.
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Cordek, DG, Bechtel, JT, Maynard, AT, Kazmierski, WM & Cameron, CE 2011, 'Targeting the NS5A protein of HCV: An emerging option', Drugs of the Future, vol. 36, no. 9, pp. 691-711. https://doi.org/10.1358/dof.2011.036.09.1641618

Targeting the NS5A protein of HCV : An emerging option. / Cordek, D. G.; Bechtel, J. T.; Maynard, A. T.; Kazmierski, W. M.; Cameron, Craig E.

In: Drugs of the Future, Vol. 36, No. 9, 09.2011, p. 691-711.

Research output: Contribution to journalReview article

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Cordek DG, Bechtel JT, Maynard AT, Kazmierski WM, Cameron CE. Targeting the NS5A protein of HCV: An emerging option. Drugs of the Future. 2011 Sep;36(9):691-711. https://doi.org/10.1358/dof.2011.036.09.1641618