Phenolic phytochemical displaying SARS-CoV papain-like protease inhibition from the seeds of Psoralea corylifolia.

Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLpro) is a key enzyme that plays an important role in SARS virus replication. The ethanol extract of the seeds of Psoralea corylifolia showed high activity against the SARS-CoV PLpro with an IC50 of value of 15 µg/ml. Due to its potency, subsequent bioactivity-guided fractionation of the ethanol extract led to six aromatic compounds (1-6), which were identified as bavachinin (1), neobavaisoflavone (2), isobavachalcone (3), 4'-O-methylbavachalcone (4), psoralidin (5) and corylifol A (6). All isolated flavonoids (1-6) inhibited PLpro in a dose-dependent manner with IC50 ranging between 4.2 and 38.4 µM. Lineweaver-Burk and Dixon plots and their secondary replots indicated that inhibitors (1-6) were mixed inhibitors of PLpro. The analysis of KI and KIS values proved that the two most promising compounds (3 and 5) had reversible mixed type I mechanisms.