Diarylheptanoids from Alnus japonica Inhibit Papain-Like Protease of Severe Acute Respiratory Syndrome Coronavirus

Abstract

The papain-like protease (PLPpro), which controls replication of the severe acute respiratory syndrome coronavirus (SARS-CoV), has been identified as a potential drug target for the treatment of SARS. An intensive hunt for effective anti-SARS drugs has been undertaken by screening for natural product inhibitors that target SARS-CoV PLPpro. In this study, diarylheptanoids 1-9 were isolated from Alnus japonica, and the inhibitory activities of these compounds against PLPpro were determined. Of the isolated diarylheptanoids, hirsutenone (2) showed the most potent PLPpro inhibitory activity, with an inhibitory concentration (IC50) value of 4.1 mu m. Structure activity analysis showed that catechol and alpha,beta-unsaturated carbonyl moiety in the molecule were the key requirement for SARS-CoV cysteine protease inhibition.