Jiri Schimer and Jan Konvalinka Pages 3389 - 3397 ( 9 )
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.
Proteinase, proteolytic processing, virostatic, rational drug design, resistance development.
, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic.