Nevirapine is an example of another class of RT inhibitor which is not a nucleoside analog. Although resistance develops rapidly when used alone, nevirapine and related drugs may prove useful in combination. These agents have a completely different mechanism of action. Like the reverse transcriptase inhibitors, protease inhibitors are expected to stop viral replication and prevent further degradation of the immune system. Several protease inhibitors are being developed by major pharmaceutical companies.
Protease inhibitors act by blocking the activation of viral proteins.
Initially, the molecular structure of HIV protease was determined using X-ray crystallography. This structure showed that HIV protease is a dimer and provided atomic coordinates of the enzyme. These coordinates are then used to make drawings of potential inhibitors bound to the enzyme. These drawings allow design and synthesis of inhibitors which are usually peptides or peptide mimetics. These inhibitors are then synthesized and tested for their ability to inhibit protease.