Protease inhibitor (pharmacology)
Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS, hepatitis C and COVID-19. These protease inhibitors prevent viral replication by selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
For natural protease inhibitors, see Protease inhibitor (biology).
Protease inhibitors that have been developed and are currently used in clinical practice include:
Given the specificity of the target of these drugs there is the risk, like with antibiotics, of the development of drug-resistant mutated viruses. To reduce this risk, it is common to use several different drugs together that are each aimed at different targets.
In addition to those non-human proteases listed above, inhibitors of human proteases may be used to treat cancer. See the articles matrix metalloproteinase inhibitor (–mastat) and proteasome inhibitor (–zomib).[1]
Other activities[edit]
Non-antiretroviral antiviral activity[edit]
A drug combination targeting SARS-CoV-2 from Pfizer, Paxlovid, was approved on December 22, 2021.[11] It is a combination of nirmatrelvir, a protease inhibitor targeted to SARS-CoV-2's 3C-like protease, and ritonavir to inhibit nirmatrelvir's metabolism.[12]
Protease inhibitors also are used to treat Hepatitis C.
Antiprotozoal activity[edit]
Researchers are investigating the use of protease inhibitors developed for HIV treatment as anti-protozoals for use against malaria and gastrointestinal protozoal infections:
Side effects[edit]
Protease inhibitors can cause a syndrome of lipodystrophy, hyperlipidemia, diabetes mellitus type 2, and kidney stones.[18] This lipodystrophy is colloquially known as "Crix belly", after indinavir (Crixivan).[19]