Diarylheptanoids from Alnus japonica inhibit papain-like protease of severe acute respiratory syndrome coronavirus

摘要

The papain-like protease (PL ~(pro)), 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 PL ~(pro). In this study, diarylheptanoids 1-9 were isolated from Alnus japonica, and the inhibitory activities of these compounds against PL pro were determined. Of the isolated diarylheptanoids, hirsutenone (2) showed the most potent PL ~(pro) inhibitory activity, with an inhibitory concentration (IC _(50)) value of 4.1 μM. Structure-activity analysis showed that catechol and α,β-unsaturated carbonyl moiety in the molecule were the key requirement for SARS-CoV cysteine protease inhibition.