The information on this site is intended for healthcare professionals in the United States and is not intended for the general public.
The information on this site is intended for healthcare professionals in the United States and is not intended for the general public.
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By 1987, AIDS was an acknowledged worldwide epidemic, with an estimated 5 to 10 million infected, and the number of dead — mostly young, vital people — climbing alarmingly. The public, the scientists, the politicians — everybody wanted an effective treatment for this terrifying disease.
Working on new information that was being gathered about the physical structure of HIV, the virus that causes AIDS, a Merck research team led by virologist Emilio Emini and biochemist Irving Sigal focused its efforts on the protein protease, which HIV uses in the process of copying itself. Disabling or inhibiting the protease, Sigal had surmised, would prevent the deadly virus from multiplying. All that was left was to prove it.
In February 1988, Nancy E. Kohl, a biochemist working on the project, confirmed Merck’s initial hypothesis. Her research showed that if HIV’s protease enzyme was inhibited, the virus would not spread from cell to cell. Recognizing the need to share this important step with the research community, Kohl, Emini, and others published their finding in the July 1988 Proceedings of the National Academy of Sciences. The Merck team was on its way down the long road toward the development of CRIXIVAN.
A protease inhibitor was not going to be an easy drug to develop, that much the team knew. Several difficult criteria would have to be met for the drug to work the way it needed to in order to be a feasible treatment for HIV in humans. First, the drug would have to be effective at preventing the virus from replicating. It would have to be well tolerated. It would also have to be available in an oral form — a challenge, considering the large size of the protease inhibitor molecules.
Fortunately, Merck had been doing research on another type of protease — renin, a protease enzyme involved in the regulation of blood pressure. Since the idea behind any protease inhibitor would be similar, the team started testing the compounds from Merck’s renin research to see if any would work as a protease inhibitor for HIV. Within a few weeks, the scientists had identified several potential candidates from the renin group, but they all quickly proved to be too weak. The hunt for a new compound was on.
