How do the protease inhibitors work?
David Ho: The protease is an enzyme for the virus. This enzyme is a chemical scissor. HIV makes its proteins in big chunks, and this enzyme cuts them into six or seven small pieces. If the enzyme does not make the cuts, the proteins are inappropriate. They won’t form the full mature progeny particle. The protease structure had been studied for a long time. Particularly in the late ’80s we realized what it looked like three dimensionally, and there’s a cavity in the middle. And inside that cavity are the enzymatic sites, or the cutting sites. And so, the big proteins could come and sit in this groove and then be cut. Well it was easy to think that if you could fill that cavity with a small chemical so the proteins could not be cut. And so many, many groups started to try to fill that cavity with small chemicals, and there were rationally designed chemicals — as well as chemicals that were done by a more empirical screening process — that would fill this cavity. And so, what protease i
