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| |  Researchers Identify Promising Drug Target in Hepatitis C Virus MADISON, N.J., June 2, 1997 -- In a potentially major step against a lethal infectious disease, scientists at Schering-Plough Research Institute have identified the structure of an enzyme essential to replication of the hepatitis C virus (HCV). In an article published in the June issue of Nature Structural Biology, the researchers report on the structure of the HCV helicase, a critical enzyme in the life cycle of the hepatitis C virus. Knowledge of how the HCV helicase is constructed will allow researchers to begin developing antiviral agents that can inhibit the helicase activity required for replication of the virus. Once developed, researchers believe that helicase inhibitors will not only be effective when used alone, but also can be used in combination with existing therapies to successfully combat the virus. HCV infects nearly 50 million people worldwide including four million Americans. In severe cases, the virus causes liver failure or liver cancer and is the cause of death in more than 12,000 people in the United States each year. "Determining the three-dimensional structure of the HCV helicase allows us to use advanced computer technology for structure-based drug design," said Patricia C. Weber, Ph.D., senior director, structural chemistry, Schering-Plough Research Institute, and one of the article's authors. "By finding a new way to target the virus, we've opened the door to the discovery of new drugs that may be more effective than anything currently available." Schering-Plough is well positioned to develop and market such new therapies. In 1991, the company received U.S. marketing clearance for Intron A(R) (interferon alfa-2b, recombinant) as a treatment for chronic, active hepatitis C. Schering-Plough also has been actively investigating treatment of the disease with Intron A in combination with Rebetol(TM) (ribavirin), a broad-spectrum antiviral drug for which the company licensed development and marketing rights from ICN Pharmaceuticals in 1995. Large-scale, multicenter trials of combined Intron A/Rebetol therapy for hepatitis C are currently under way in Europe and the United States. Results of a Phase II clinical study demonstrate that the two-drug combination is significantly more effective than alpha interferon alone in eradicating HCV. Researchers at Schering-Plough Research Institute are designing small molecule inhibitors of the newly-defined HCV helicase, which is the second HCV enzyme to be analyzed by X-ray crystallography. Research on the helicase complements the company's ongoing efforts in the design of HCV protease inhibitors. Like the HCV elicase, the HCV protease, which was the first HCV enzyme to be identified, plays a vital role in the virus' replication. HCV is transmitted chiefly by intravenous drug abuse, tattooing and body piercing, sexual contact with an infected partner, organ transplantation and hemodialysis. HCV often infects the body "silently," without causing symptoms. As a result, up to 95 percent of people with hepatitis C are unaware that they are infected. In the United States, it has been estimated that as many as 60 to 90 percent of those infected with HCV each year go on to develop chronic hepatitis C, which often leads to cirrhosis. The result can be liver failure or liver cancer. Chronic hepatitis C is the nation's leading cause of liver cancer, and, according to the American Liver Foundation, is also the chief reason for liver transplantation. Schering-Plough Research Institute is the pharmaceutical research and development arm of Schering-Plough Corporation, a research-based company engaged in the discovery, development, manufacturing and marketing of pharmaceutical and health care products worldwide.
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