Potent SARS inhibitors identified

Small-molecule agents that represent the most potent inhibitors yet known of the protease of severe acute respiratory syndrome virus have been identified. SARS, a contagious and potentially fatal respiratory condition caused by a coronavirus, was first reported in Asia several years ago and still cannot be effectively treated. Its protease plays an essential role in viral replication and is thus a promising target for anti-SARS therapeutics. Although a few inhibitors have been found, none are highly potent (that is, none have activities in the low nanomolar range), and no preclinical testing of the agents has been reported. Now a series of potent small-molecule inhibitors, like the 7.5-nM agent shown, have been identified by Po-Huang Liang of Academia Sinica, Taipei, Taiwan; Chi-Huey Wong of Scripps Research Institute; and coworkers (Chem. Biol. 2006, 13, 261). The benzotriazole esters act as suicide inhibitors by bonding irreversibly to a key site on the virus.