Protease inhibitor (pharmacology)

Protease inhibitor (pharmacology)

:"For natural protease inhibitors, please see protease inhibitor (biology)"

Protease inhibitors (PIs) are a class of medications used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevents viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons.

Protease inhibitors have been developed or are presently undergoing testing for treating various viruses:
* HIV/AIDS: antiretroviral protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir etc.)
* Hepatitis C: experimental agents: "BILN 2061 (All clinical trials of BILN 2061 have been suspended due to cardiac issues)", "VX 950" (trade name Telaprevir), or SCH 503034 [FDA Grants Fast Track Designation To Oral HCV Protease Inhibitor SCH 503034 [] ]

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.


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.cite journal |author=Dunn LA, Andrews KT, McCarthy JS, "et al" |title=The activity of protease inhibitors against Giardia duodenalis and metronidazole-resistant Trichomonas vaginalis |journal=Int. J. Antimicrob. Agents |volume=29 |issue=1 |pages=98–102 |year=2007 |pmid=17137752 |doi=10.1016/j.ijantimicag.2006.08.026]
* The drugs saquinavir, ritonavir, and lopinavir have been found to have anti-malarial properties.cite journal |author=Andrews KT, Fairlie DP, Madala PK, "et al" |title=Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria |journal=Antimicrob. Agents Chemother. |volume=50 |issue=2 |pages=639–48 |year=2006 |pmid=16436721 |doi=10.1128/AAC.50.2.639-648.2006]
* A cysteine protease inhibitor drug was found to cure Chagas disease in mice.cite journal |author=Doyle PS, Zhou YM, Engel JC, McKerrow JH |title=A Cysteine Protease Inhibitor Cures Chagas' Disease in an, Immunodeficient Murine Model of Infection |journal= Antimicrobial Agents and Chemotherapy|volume= 51|issue= |pages=3932|year=2007 |pmid=17698625 |doi=10.1128/AAC.00436-07]

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). [ cite journal|url=|author= J.J. Gills et al. |title=Nelfinavir, A Lead HIV Protease Inhibitor, Is a Broad-Spectrum, Anticancer Agent that Induces Endoplasmic Reticulum Stress, Autophagy, and Apoptosis In vitro and In vivo|journal= Clinical Cancer Research |volume=13|pages=5183–94|year=2007 |doi=10.1158/1078-0432.CCR-07-0161 |pmid=17785575] cite journal|url= |title=HIV-1 protease inhibitors nelfinavir and atazanavir induce malignant glioma death by triggering endoplasmic reticulum stress|journal= Cancer Research |volume=67|pages=10920–8|year=2007 |doi=10.1158/0008-5472.CAN-07-0796 |author=Pyrko, P. |pmid=18006837] 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.


* A [ brief history] of the development of protease inhibitors by Hoffman La Roche, Abbott, and Merck

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