Recent advances in the design of HIV proteinase inhibitors.

Inhibition of HIV proteinase is currently one of the most widely studied approaches for chemotherapeutic intervention in the treatment of AIDS. A range of inhibitors of this essential enzyme has been designed from detailed knowledge of its mechanism of action and cleavage sites. These inhibitors have been classified according to their derivation. All are transition-state analogues and contain a hydroxyethylene, hydroxyethylamine, phosphinate or symmetrical moiety. Many of these inhibitors have high selectivity for the viral enzyme and significant antiviral activity. Advances in the design of HIV proteinase inhibitors that have been reported in the past year are reviewed.