June/July 2017 

Know your drugs and classes of HCV treatment

In this issue of TreatmentUpdate we discuss several emerging treatments for hepatitis C virus (HCV). Here is a brief guide to some drugs and the classes to which they belong.

Know your drugs and classes

Treatments for HCV available in high-income countries today are highly effective, with rates of cure generally greater than 90%. In the years ahead, even more powerful combinations of all-oral anti-HCV drugs, called direct-acting antivirals (DAAs), will become available to treat all major strains of HCV.

Proteins and enzymes

There are many steps that are needed within an HCV-infected cell so that copies of HCV can be made. These steps involve proteins and enzymes. A combination of drugs that target multiple proteins and enzymes makes for a more effective regimen than one single drug alone. HCV proteins and enzymes are targets of DAAs and serve as ways to group DAAs. This grouping is also used when sorting strains of HCV that are resistant to DAAs.

NS3 and NS4A

The enzyme called NS3 is part of a vital step in the production of copies of HCV. A protein called NS4A, made by HCV-infected cells, enhances the activity of NS3. Examples of drugs that work by attacking NS3 and/or NS4A include the following:

  • asunaprevir (Sunvepra)
  • grazoprevir (in Zepatier)
  • paritaprevir (in Holkira Pak)
  • simeprevir (Galexos)
  • glecaprevir (formerly ABT-493)
  • voxilaprevir (formerly GS-9857)

All of the above-listed drugs are called protease inhibitors.


The enzyme NS5B is part of another vital step in the creation of copies of HCV. NS5B inhibitors are divided into subclasses such as nukes (sofosbuvir) and non-nukes (dasabuvir, in Holkira Pak).


Researchers are not certain about the exact role of this protein, but it is critical to the production of HCV. Inhibitors of NS5A include the following:

  • daclatasvir (Daklinza)
  • ledipasvir (in Harvoni)
  • elbasvir (in Zepatier)
  • ombitasvir (in Holkira Pak)
  • velpatasvir (in Epclusa)
  • pibrentasvir (formerly ABT-530)

—Sean R. Hosein


Gotte M, Feld JJ. Direct-acting antiviral agents for hepatitis C: structural and mechanistic insights. Nature Reviews. Gastroenterology & Hepatology. 2016 Jun;13(6):338-51.