By Deborah Gilbert
News and Information Services
U-M scientists have discovered two new drugs which may prove highly effective in the fight against HCMV (human cytomegalovirus).
HCMV can lead to blindness in AIDS patients and pneumonia in bone marrow transplant patients. The virus is also a leading cause of birth defects in the United States.
The drugs---TCRB and a derivative, BDCRB---are benzimidazole nucleosides. In cell cultures, the two drugs reduced amount of virus by 100,000-fold, and at concentrations that were not toxic to normal cells.
Both drugs are highly specific for HCMV and are less toxic to bone marrow than ganciclovir, the drug currently used to treat HCMV. Bone marrow generates white and red blood cells.
Roughly 50 percent of the U.S. population carries the virus, but it is relatively harmless to people whose immune systems are intact. The virus is transmitted in saliva and urine.
The U-M research team reported their findings Oct. 12 at the Interscience Conference on Antimicrobial Agents and Chemotherapy in California.
"We are particularly excited about the drugs because, in cell culture, they have proven effective against cytomegaloviruses that are resistant to ganciclovir," said Leroy B. Townsend, who is the Albert B. Prescott Professor of Medicinal Chemistry and professor of chemistry, and John C. Drach, professor of dentistry and of medicinal chemistry.
The new drugs are unusual because, unlike ganciclovir, which inhibits DNA synthesis, they block the virus later in the replication process when the parts of the virus are assembled. "We are uncertain of the exact mechanism, but it may be that the drugs deform one or several parts of the virus so they don't fit together," the researchers explained.
The research project is funded by the National Institute of Allergy and Infectious Diseases. Drach and Townsend's colleagues in the study include Charles Shipman, professor of dentistry; Dean S. Wise, associate research scientist, College of Pharmacy; and Steven R. Turk and M. Reza Nassiri, assistant research scientists, Department of Biologic and Materials Sciences, School of Dentistry.
Earl R. Kern, research professor, University of Alabama-Birmingham, and Karen K. Biron, research scientist, Burroughs Wellcome Co., also participated. Biron is coordinating preclinical trials with the drugs.