Protease inhibitor (pharmacology)

Protease inhibitors (PIs) are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new virions.

Protease inhibitors have been developed or are presently undergoing testing for treating various viruses: Given the specificity of the target of these drugs there is the risk, as in 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.
 * HIV/AIDS: antiretroviral protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir, amprenavir etc.)
 * Hepatitis C: Boceprevir
 * Hepatitis C: Telaprevir

Antiretrovirals
Protease inhibitors were the second class of antiretroviral drugs developed. In all cases, patents remain in force until 2010 or beyond.

Antiprotozoal Activity
Researchers are investigating the use of protease inhibitors developed for HIV treatment as anti-protozoals for use against malaria and gastrointestinal protozoal infections:


 * A combination of ritonavir and lopinavir was found to have some effectiveness against Giardia infection.
 * The drugs saquinavir, ritonavir, and lopinavir have been found to have anti-malarial properties.
 * A cysteine protease inhibitor drug was found to cure Chagas disease in mice.

Anticancer Activity
Researchers are investigating whether protease inhibitors could possibly be used to treat cancer. For example, nelfinavir and atazanavir are able to kill tumor cells in culture (in a Petri dish). This effect has not yet been examined in humans; but studies in laboratory mice have shown that nelfinavir is able to suppress the growth of tumors in these animals, which represents a promising lead towards testing this drug in humans as well.

Inhibitors of the proteasome, such as Velcade/Bortezomib are now front-line drugs for the treatment of various cancers, notably Multiple Myeloma.