HIV protease (PR) is a key target for antiviral drugs, and HIV protease inhibitors (PIs) are a prime example of successful
structure-based drug design. PIs show clear therapeutic benefits, but their efficacy can be compromised by poor bioavailabilitity, unwanted
side effects, and most importantly, development of antiviral drug resistance. Therefore, the quest for novel, highly active compounds
with improved resistance profiles, better pharmacokinetic properties, and fewer adverse effects continues. In particular, the problem
of cross-resistance could be circumvented by identifying novel compounds that show different binding modes to HIV PR than the
current clinical inhibitors.