Scientists at the US Department of Energy’s Brookhaven National Laboratory have set the stage for the rapid identification of compounds to fight against severe acquired respiratory syndrome (SARS), the atypical pneumonia responsible for about 800 deaths worldwide since first recognized in late 2002. Researchers from Brookhaven’s biology department and the National Synchrotron Light Source (NSLS) characterized a component of the virus that will be the target of new anti-SARS virus drugs. The results were published online by Biochemistry on November 17, 2006.
“Although vaccines against viruses are very effective, vaccines for viruses that mutate rapidly—such as the viruses that cause SARS, AIDS, and bird flu—are much more difficult to obtain,” said Brookhaven biologist Walter Mangel, the lead author of the paper. “Even if a vaccine is available, antiviral agents are important in stopping the spread of highly infectious viruses. If antiviral agents for SARS had been available, they could have been used to contain the outbreak to the initial site of the infection.”
The researchers studied the SARS main proteinase, an enzyme used by the virus during infection to cut newly made viral proteins into gene-sized, functioning pieces. If the proteinase is prevented from working, the virus infection is aborted. Previous studies have revealed that the proteinase is inactive when in the form of single molecules. But once two of those molecules bind together to make what is called a dimer, the enzyme becomes active and is able to play its role in SARS virus reproduction. The challenge for researchers, and the focus of the Brookhaven study, was to determine the concentration at which individual proteinase molecules form active dimers. Knowing this concentration, for which estimates at other laboratories have varied greatly, would allow researchers to search for anti-SARS drugs more efficiently by ensuring that the proteinase used in tests is initially in its active form.