Flavonoids Derived from the Roots of Inhibit the Activity of SARS-CoV Papain-like Protease.

Despite the now infamous coronavirus disease outbreaks caused by severe acute respiratory syndrome coronavirus (SARS-CoV), this virus continues to be a threat to the global population. Although a huge research effort has targeted SARS-CoV, no report exists regarding natural small molecules targeting one of its key enzymes, papain-like protease (PLpro). In this study, nine flavonoids displaying SARS-CoV PLpro inhibitory activity were isolated from the root bark of . The compounds were identified as erythrabyssin II (), lespebuergine G4 (), 1-methoxyerythrabyssin II (), bicolosin A (), bicolosin B (), bicolosin (), xanthoangelol (), (±)-lespeol (), and parvisoflavanone (). Most compounds (- and -) inhibited SARS-CoV PLpro activity in a dose-dependent manner, with their s ranging from 5.56 to 75.37 μM. The structure-activity analysis of pterocarpans (-) showed that activity was enhanced by C1-OCH, but it was reduced by C8-CH. A mechanistic analysis revealed that all inhibitors were noncompetitive. Some of the key compounds isolated in this study are pterocarpans, which are abundantly present in the Leguminosae family. Overall, a rich source of SARS-CoV papain-like protease inhibitors was identified in this study.