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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. Protease inhibitors that have been developed and are currently used in clinical practice include:
Protease inhibitors may be classified either by the type of protease they inhibit, or by their mechanism of action. In 2004 Rawlings and colleagues introduced a classification of protease inhibitors based on similarities detectable at the level of amino acid sequence. [4]
Protease inhibitor can refer to: Protease inhibitor (pharmacology) : a class of medication that inhibits viral protease Protease inhibitor (biology) : molecules that inhibit proteases
Tipranavir is a nonpeptidic HIV-1 protease inhibitor [11] and reached the market in 2005. [18] Unlike other HIV protease inhibitors on the market, tipranavir was developed from a nonpeptidic coumarin template and its antiprotease activity was discovered by high-throughput screening. [23]
The 3C-like protease inhibitor ensitrelvir received authorization to treat COVID-19 in Japan in 2022. [19] [20] In 2022, an ultralarge virtual screening campaign of 235 million molecules was able to identify a novel broad-spectrum inhibitor targeting the main protease of several coronaviruses. It is unusually not a peptidomimetic. [21]
AEBSF or 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride is a water-soluble, irreversible serine protease inhibitor with a molecular weight of 239.5 Da. It inhibits proteases like chymotrypsin, kallikrein, plasmin, thrombin, and trypsin. The specificity is similar to the inhibitor PMSF, nevertheless AEBSF is more stable at low pH values ...
Examples of Kunitz-type protease inhibitors are aprotinin (bovine pancreatic trypsin inhibitor, BPTI), Alzheimer's amyloid precursor protein (APP), and tissue factor pathway inhibitor (TFPI). Kunitz STI protease inhibitor, the trypsin inhibitor initially studied by Moses Kunitz, was extracted from soybeans.
Epoxomicin is a naturally occurring selective inhibitor. [15] MG132 is a synthesized peptide commonly used for in vitro studies. Beta-hydroxy beta-methylbutyrate is a proteasome inhibitor in human skeletal muscle [16] [17] in vivo. [18] PI31 acts as a 20S proteasome inhibitor used for proteostasis that occurs naturally in the human body. [19]