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

Abstract

The papain-like protease (PL^pro), which controls replication of the severe acute respiratory syndrome (SARS) coronavirus, 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 IC₅₀ 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.