Diarylheptanoids from Alnus japonica inhibit papain-like protease of severe acute respiratoy syndrome coronavirus = 오리나무로부터 분리한 diarylheptanoids 화합물들의 사스 코로나 바이러스 PLpro 저해활성

Abstract

The papain-like protease (PLpro), 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 PLpro. In this study, diarylheptanoids 1-9 were isolated from Alnus japonica, and the inhibitory activities of these compounds against PLpro were determined. Of the isolated diarylheptanoids, hirsutenone (2) showed the most potent PLpro inhibitory activity, with an inhibitory concentration (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.