Currently, there are no effective antiviral agents or vaccines for SARS, which killed almost 800 people in an epidemic in 2002-2003.
On the basis of their success, the researchers have received an $8 million grant from the National Institute of Allergy and Infectious Diseases to develop protease inhibitors that would block key enzymes in the SARS virus and hamper its advance. Protease inhibitors, a class of drugs capable of disrupting enzymes that digest proteins, have been successfully used to thwart the human immunodeficiency virus, which causes AIDS.
"Data from SARS patients indicate that replication of the virus peaks 10 days after the onset of fever," said Michael Johnson, director of the Center for Pharmaceutical Biotechnology in the UIC College of Pharmacy and the study's principal investigator. "By administering protease inhibitors early, when feverish symptoms have started, the drugs could reduce the viral load and ameliorate the disease."
Like HIV, the SARS virus multiplies rapidly, hijacking the machinery of the cells it infects to clone itself over and over again.
One of the first steps in that process is the production of a long chain of proteins, all of which are needed for the virus to propagate. Two enzymes, or proteases, clip the chain to release the individual proteins, the parts needed to assemble a mature virus.
These two proteases -- called 3CLpro and PLpro -- are UIC's targets for drug therapy.
"If we can block 3CLpro and probably PLpro, then we can stop the SARS virus from replicating," Johnson said.
Under the grant, Andrew Mesecar, associate professor of pharmacy, will study details of the three-dimensional structure of the two enzymes using x-ray crystallography.