Abstract
The aspartic protease of the human immunodeficiency virus is one of the most extensively studied enzymes known to man. More than 200 X-ray structures of the protein in the presence or absence of ligands or inhibitors have been determined to date, and the symmetric depictions of this dimeric enzyme have become one of the icons of modern structural biology.
The HIV protease is crucial for the production of infectious viral particles, and PR inhibitors are potent and specific anti HIV drugs. The successful rational design of HIV PIs is one of the most striking examples of structure-based drug design.
In this chapter, we will explain why the design of novel, potent PIs is still urgently needed and that derivatives of bis(dicarbollide)(1-) ion [(1,2-C2B9H11)-3,3'-Co(III)](1-), a compound well known to the carborane community, act as unexpected class of specific HIV PIs. We shall review their activity, specificity, mechanism of action, and binding mode to HIV protease