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Enzyme inhibitors block replication of SARS virus

ve been looking at other Liponavir-related compounds for similar blocking effects. During these experiments, they found that a group of catalyzing agents used to help promote chemical reactions in the laboratory were actually more powerful in blocking the SARS protease than either the Lopinavir or any of the target compounds.

These organic compounds are called benzotriazole esters. The esters entered the SARS protease site, formed an intermediary compound, then inactivated the SARS enzyme. The findings were confirmed using mass spectrometry analysis of the enzyme intermediary.

"These benzotriazole esters are relatively stable and act as suicide inhibitors," Wong said. "They block the enzyme, are transformed through a co-valent bond, and are unable to get out."

Wong said the findings published today provide better insight into the mode of action of the enzyme, which may lead to development of a drug against SARS. The findings were made by using rapid drug discovery techniques developed in the Wong lab to screen large numbers of weak enzyme inhibitors, and then attaching additional compounds to look for stronger reactions.

Research Associate Chung-Yi Wu, a member of the Wong lab, is the paper's lead author. He said the finding was unexpected.

"We wanted to improve Liponavir activity," Wu said. "But we found this very surprising and serendipitous result."


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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
28-Mar-2006


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