What is a Protease Inhibitor?

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  • Written By: Mary McMahon
  • Edited By: O. Wallace
  • Last Modified Date: 11 November 2019
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A protease inhibitor is a type of medication which is designed to interfere with the activity of protease, a type of enzyme used by many viruses to reproduce themselves. Protease is most notably utilized by the human immunodeficiency virus (HIV) to replicate itself, and it is also involved in the replication of hepatitis C. By developing drugs which target protease, pharmaceutical companies can market products which will reduce the overall viral load in patients, even if they cannot cure viral infections, and a reduced viral load will help a patient stay healthier longer.

The first protease inhibitor was approved for sale in 1995, and several other products quickly followed. Some examples of protease inhibitors on the market include nelfinavir, saquinavir, rionavir, and indinavir. These drugs are classically used in combination therapy with other drugs and additional protease inhibitors to attack viral infections; as of 2009, protease inhibitors had only been approved for use against HIV. These drugs have also been explored as potential experimental cancer treatments, as they may be able to inhibit the growth of cancerous tumors.

Combination therapy takes advantage of multiple drugs which have different effects to create a multiple-pronged assault. By combining a protease inhibitor with another protease inhibitor, the risk of developing resistant viral strains is also reduced. Because the protease can change each time a virus replicates, using multiple inhibitors ensures that random mutations which resist one form of protease inhibitor will be mopped up by another.


Using combination therapy to manage HIV infection requires taking a cocktail of drugs which can be complicated and expensive to manage. Patients need to be careful about taking all of their drugs, and following a specific schedule. Noncompliance with combination therapy puts a patient at risk of getting sicker, and also could contribute to the generation of drug-resistant strains of HIV which might be passed on to others, making HIV/AIDS treatment harder in the future.

Several side effects are associated with protease inhibitors. One of the most serious is a rise in blood sugar, and the development of diabetes. These drugs have also been implicated in liver toxicity, a common problem with drugs which are taken in high dosages and in the long term because the liver eventually becomes unable to process them. A protease inhibitor also interferes with the way the body processes and stores fat, causing an increase in cholesterol levels and the formation of unusual fat deposits.


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