Difference Between Protease Inhibitors & Antiviral Drugs for Hepatitis C Treatment

Around the world, millions of people are affected by the Hepatitis C virus every year. Hepatitis C is an infection that attacks the liver and causes inflammation. The hepatitis C virus does not cause any symptoms until the time it reaches a chronic stage; therefore, many people remain unaware that they have contracted the Hep-C virus. The Hep-C virus spreads through body fluids or through the blood of an infected person, thereby spreading commonly through sexual intercourse, sharing needles and drugs, during the birthing process where a mother can pass it on to a child, etc. If chronic hepatitis C is not treated, then it can eventually lead to liver damage and even damage other organs as well. There are many different types of hepatitis C treatments that work by eliminating the virus from the body. The evolution of hepatitis C treatments has come rapidly; and today, protease inhibitors and antiviral drugs are the two most common forms of treatment for hepatitis C. Let us take a look at how these treatment options compare against each other.

Protease Inhibitors vs. Antiviral Drugs for Hepatitis C Treatment: Differences Based on Definitions & their Action

Antiviral Drugs for Treating Hepatitis C

Antiviral drugs are a class of medications that are used for treating viral infections. These drugs work by inhibiting the development of the Hepatitis C virus itself, rather than destroying the virus.

To treat hepatitis C, the usual treatment that has been used for many years is a combination of two antiviral medications. These drugs are specifically designed to get rid of the HCV. Pegylated interferon (PEG) and ribavirin are the two antiviral drugs that are used to treat hepatitis C. While PEG is administered as a weekly injection, ribavirin pills need to be taken twice a day. This antiviral therapy for Hepatitis C treatment takes around six months to a year to finish. The therapy is sometimes also referred to as PEG/riba.

Protease Inhibitors for Treating Hepatitis C

Protease inhibitors are also a class of antiviral drugs itself. However, they differ from the common antiviral drugs in the manner in which they work. Protease inhibitors prevent the virus from replicating by binding to other viral proteases. These are a newer class of drugs that also block the proteolytic cleavage of protein precursors. These protein precursors are what the Hepatitis C virus requires for producing more infectious viral particles. These drugs are now widely being used for the treatment of hepatitis C and HIV/AIDS.

Protease Inhibitors vs. Antiviral Drugs: Differences Based on Side Effects

Side Effects of Antiviral Drugs for Treatment of Hepatitis C

PEG/riba treatments have severe side effects. These may include:

Side Effects of Protease Inhibitors for Treatment of Hepatitis C

Some of the common side effects of protease inhibitors include:

Protease Inhibitors vs. Antiviral Drugs: Comparing New Developments

Development of Antiviral Drugs for Treating Hepatitis C

Since 2011, there has been an improvement in the development of antivirals as a new class of drugs was introduced known as direct-action antivirals. These direct-acting antivirals work by destroying the virus directly by interfering with the virus’ ability to reproduce and spread in the body. These are similar to the working mechanism of protease inhibitors, but protease inhibitors are a class of drugs further advanced than direct-acting antivirals. It has also been seen that direct-acting antivirals are more effective in curing more types of hepatitis C when compared to PEG/ribavirin alone. Interferon and ribavirin were typically found to be effective against type 1 hepatitis C, whereas, these direct-acting antivirals are shown to be effective against most types of hepatitis C. Similar to protease inhibitors, these direct-acting antivirals also have lesser side effects.

There are three classes of direct-acting antivirals that have been approved till date. These include:

  • NS3/4A protease inhibitors
  • NS5A inhibitors
  • Polymerase inhibitors – these include non-nucleoside inhibitors and nucleotide inhibitors

A combination of these three drugs is used for treating HCV, depending upon which genotype of the disease the patient is suffering from. Due to the increased effectiveness of direct-acting antivirals and lesser side effects, direct-acting antivirals have now become the standard for hepatitis C treatment, particularly for people who have reached the chronic stage of the disease already. In some cases, the PEG/riba therapy is still used, but in combination with direct-acting antivirals only.

The drawback of direct-acting antivirals is that some of these drugs can interfere with other medications and lead to some severe reactions. Medications they tend to interfere with include cholesterol-lowering statin medications or even some drugs used for erectile dysfunction.

Development of Protease Inhibitors for Treating Hepatitis C

Protease inhibitors are a new generation of direct-acting antivirals. There are currently two types of protease inhibitor drugs available for the treatment of hepatitis C. These include simeprevir (brand name Olysio and Sovriad), and paritaprevir. Both of these drugs are used in combination with other medications, depending on the type of hepatitis C the patient is suffering from. The first generation protease inhibitors, telaprevir and boceprevir, are no longer used in the treatment of Hepatitis C. Similar to the first generation antiviral drugs, protease inhibitors are also known to be more effective in treating genotype 1 of Hepatitis C. The biggest benefit of using protease inhibitors is that they cause less severe and fewer side effects.


There is no ‘one-size-fits-all’ option when it comes to treatment options for hepatitis C. Since there are many genotypes of the disease, the treatment has to be tailored accordingly. It is important to understand that your doctor will determine the best course of treatment for you based on several factors, the most important one being which genotype of hepatitis C you have. Not all drugs work on all the genotypes of hepatitis C. The medication that will be selected for you by your doctor will also depend upon the extent of liver scarring (cirrhosis) or liver damage you have. Research is moving rapidly in the field of hepatitis C treatment and as researchers develop new treatments, your doctor may change the combinations of your medications accordingly.

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Team PainAssist
Team PainAssist
Written, Edited or Reviewed By: Team PainAssist, Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:June 26, 2018

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