Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARS-CoV

摘要

Abstract Two viral proteases of severe acute respiratory syndrome coronavirus (SARS-CoV), a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro) are attractive targets for the development of anti-SARS drugs. In this study, nine alkylated chalcones ( 1 – 9 ) and four coumarins ( 10 – 13 ) were isolated from Angelica keiskei, and the inhibitory activities of these constituents against SARS-CoV proteases (3CLpro and PLpro) were determined (cell-free/based). Of the isolated alkylated chalcones, chalcone 6 , containing the perhydroxyl group, exhibited the most potent 3CLpro and PLpro inhibitory activity with IC₅₀ values of 11.4 and 1.2?μM. Our detailed protein-inhibitor mechanistic analysis of these species indicated that the chalcones exhibited competitive inhibition characteristics to the SARS-CoV 3CLpro, whereas noncompetitive inhibition was observed with the SARS-CoV PLpro.