“Serendipity may be the best description of this crucial finding!”, says Dr. Jim-Min Fang regarding the SARS protease inhibitor found by a group of researchers aiming at drug discovery for SARS.

The group led by Dr. Chi-Huey Wong, has identified a compound that will cause suicidal effects of the SARS virus. This finding is published by Chemistry & Biology journal in its March 2006 issue.

The SARS research team is led by Dr. ChiHuey Wong

The SARS pandemic that caused global panic during 2003 and 2004 has been known to be an infection with a novel human coronavirus SARS-CoV. Until now, there is no effective antiviral for it. However, scientist has already found out in SARS virus itself, there is a protease named as 3CLpro which plays a major role in the viral replication, and thus has become an attractive target for the development of SARS therapeutics.

Wong’s team has been developing potent anti-SARS agents by using the strategy of combinatorial reaction in microtiter plates followed by screening in situ. They reported the discovery of a new class of mechanism-based irreversible inactivators which out-performed other compounds.

The main ingredient has been benzotriazole esters, which was originally considered acylating agents, i.e., an intermediate chemical produced during the making of target compounds for drug discoveries. Researchers have discovered that part of 3CLpro joins benzotriazole ester and forms an irreversible bonding state and hence loses its power in reproducing. Researchers call this effect a suicidal inhibition.

Binding of the new found compound and SARS 3CL

The finding can be explored further as scientists can modify the known compound in search for an ultimate drug candidate. This is another achievement of the Academia Sinica SARS team, including Dr. Po-Huang Liang, Dr. Chung-Yi Wu, and others from the Genomics Research Center and Dr. Jim-Min Fang of Department of Chemistry from National Taiwan University.