Protease Inhibitors: Emphasizing Functional Aspects of Aspartic Protease Inhibitors

Aspartic proteases are relatively a small group of proteolytic enzymes. Over the last decade, they have received tremendous research interest as potential targets for pharmaceutical intervention as many have been shown to play significant roles in physiological and pathological processes. Despite numerous efforts, however, the only inhibitors for aspartic proteases currently in the market are directed against the HIV protease of viral origin. Nevertheless, several inhibitors including those targeting reninangiotensin system and β-secretase are in clinical or preclinical developments and few other aspartic proteases are discussed as potential drug targets. Currently the research strategies are focusing on the need for improved comprehension of protease-regulated cascades, along with precise selection of targets and improved inhibitor specificity. There is plethora of synthetic inhibitory compounds targeting aspartic proteases; however there are few reports documented in literature on biologic inhibitors from microorganisms. Protease inhibitors (PIs) are widely distributed in the plant kingdom. One of the important defense strategies that are found in plants to combat predators involves PIs which are particularly effective against phytophagous insects and microorganisms. In plants, these PIs act as anti-metabolic proteins, which interfere with the digestive process of insects. The defensive capabilities of PIs rely on inhibition of proteases present in insect guts or secreted by microorganisms, causing a reduction in the availability of amino acids necessary for their growth and development. The present chapter is a comprehensive state-of-the-art review describing the aspartic protease inhibitors from microbial and plant origin. In addition, the chapter highlights the therapeutic perspectives of aspartic protease inhibitors and biocontrol aspects of protease inhibitors with special emphasis on aspartic protease inhibitors.