Proteases are a class of enzymes that degrade proteins by cutting the bond between the amino acids that make up the protein. Trypsin and chymotrypsin were the first proteases to be identified. Scientists studied the structure of these enzymes by doing a comparative study of the amino acid sequences of these enzymes and by using X-ray crystallography. As research continued, scientists realized that enzymes act on specific molecules called substrates by binding to them at active sites (see An Enzyme with Bite). Thus, enzyme inhibitors can be developed which have greater affinity for the active site than the natural substrate, and hence will win the fight to bind with the enzyme. Intensive research led to the development of several effective protease inhibitors (see Inhibiting by Design).

The AIDS epidemic hit in the early 1980s and the responsible virus, HIV, was recognized to be a retrovirus by the mid-1980s. While researching cancer treatments in the 1970s, scientists had discovered that retrovirus proteins are not made as individual units, but rather as complexes which then have to be cut up by a protease (see The AIDS challenge). Efforts were now focused on stopping the HIV virus. Initially, scientists attempted to keep HIV from multiplying once it entered a cell by stopping the replication of the viral genes. This led to the development of the drug AZT. Unfortunately, scientists found that the HIV virus quickly became resistant to AZT. Meanwhile, scientists also were attempting to inhibit or stop the manufacture of viral proteins and were researching the structure of the HIV protease (see Halting Viral Replication). In 1996, scientists found that a cocktail made with protease inhibitors and AZT type drugs was very effective (see Hitting the Target). Despite their effectiveness, protease inhibitors have some drawbacks such as severe side effects. But research continues and scientists are applying protease inhibitor drugs to other diseases (see New Vistas).

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