The treatment of hepatitis C virus infections has taken a major step forward with the U.S. Food and Drug Administration’s approval of two new drugs, telaprevir and boceprevir, for managing the disease. Blocking the same viral protein as the first ­anti-HIV drugs, they are also the latest chapter in an ongoing story of medical success.

Telaprevir and boceprevir are protease inhibitors, thwarting the activity of key viral enzymes. The first in this class of drugs was saquinavir, available since 1995 for the treatment of HIV. Several protease inhibitors have subsequently been developed for HIV, but the new hepatitis C drugs are the first to tackle other viruses.

The protease targeted by the anti-HIV and anti–hepatitis C drugs is involved in a process called cleavage. These viruses insert their RNA into the host cell. That genetic information is then used to create a single, long strand of proteins, called a polyprotein, that must be chopped up, or cleaved, into its distinct components for the virus to replicate. Protease enzymes perform that job. Protease inhibitors bind to the active part of a key protease, rendering it unable to cleave the polyprotein.

After the success of protease inhibitors in HIV, research groups around the world began investigating whether the same mechanism would work for hepatitis C. In 1997 Charles M. Rice, now head of the laboratory of virology and infectious disease at the Rockefeller University, showed that mutating the viral protease in hepatitis C–infected chimpanzees stopped the virus, the first clue about the enzyme’s importance. Subsequently, molecular virologist Ralf Bartenschlager of the University of Heidelberg in Germany confirmed the vital role of the protease in hepatitis C replication. Many studies later protease inhibitors were ready for com­mercial hepatitis C drug developers. In trials, telaprevir and boceprevir elicited response rates that were 20 to 30 percent higher than those seen with the older regimen—pegylated interferon plus ribavirin—by itself, an encouraging result.

Second-generation inhibitors are already in development, and the enzyme will likely be a target for other infectious diseases. Protease inhibitors may also be tested against cancer, particularly considering their earlier efficacy in HIV-related Kaposi’s sarcoma. 

How Did Hepatitis C Emerge in Humans?
Although it has existed for centuries, hepatitis C was identified just over 20 years ago, and scientists have been puzzling about its origins ever since. In May, Columbia University Medical Center pathologist W. Ian Lipkin and his colleagues identified a hepatitis C–like virus in dogs for the first time, suggesting the disease may have jumped to humans through contact with man’s best friend 500 to 1,000 years ago, long after dogs were first domesticated.

This article was originally published with the title Going Viral.

4 Comments

1. 1. HubertB 03:17 PM 8/5/11

   If the drug worked 14 years ago, why did it take so long to let so many humans die before others were allowed to take it?

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2. 2. bucketofsquid in reply to HubertB 09:44 AM 8/12/11

   Probably because before we had sufficient testing processes many drugs hit the market, killed thousands and did irrepairable harm and then disappeared as quickly as they arrived. This way is better.

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3. 3. pressingtheissue 11:23 AM 12/31/11

   I agree that it's better to wait and have more confidence of efficacy and safety. I have Hepatitis C genotype 1a and have been waiting for this treatment regiment to come out. Since my liver is in good health, (not perfect though) my doctor said I could wait for this treatment to be more available. Now I think that it's time to get started. While waiting I have been taking Liv-52 and some potent forms of Milk Thistle to help my liver stay as healthy as possible. Great article!
   <a href="http://www.pressingtheissue.com/2011/12/hepatitis-c-triple-therapy-new-hep-c-treatment">New Hep C Treatment</a>

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4. 4. JennNYC 04:15 PM 2/7/13

   One thing that I think is not very clear from your article is that HIV protease and HCV protease (also known as NS3) are two different enzymes. Just because a drug works against HIV protease does not mean that it will work against HCV protease. The enzymes perform similar jobs, but the enzymes themselves are quite different. Therefore, the success of HIV protease inhibitors provided a good proof of principle for HCV protease inhibitors, but there was still a lot of work to be done on HCV protease to find potential inhibitors.
   
   Also, protease inhibitors were not the first type of HIV drugs as you suggest in the first paragraph. That category belongs to reverse transciptase inhibitors, the first of which (zidovudine)was approved by the FDA in 1987.

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