Flavonoids Derived from the Roots of <i>Lespedeza bicolor</i> 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...

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Bibliographic Details
Main Authors: Hyun Sim Woo, Kon Ho Lee, Ki Hun Park, Dae Wook Kim
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Plants
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Online Access:https://www.mdpi.com/2223-7747/13/23/3319
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Summary: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 <i>Lespedeza bicolor</i>. The compounds were identified as erythrabyssin II (<b>1</b>), lespebuergine G4 (<b>2</b>), 1-methoxyerythrabyssin II (<b>3</b>), bicolosin A (<b>4</b>), bicolosin B (<b>5</b>), bicolosin (<b>6</b>), xanthoangelol (<b>7</b>), (±)-lespeol (<b>8</b>), and parvisoflavanone (<b>9</b>). Most compounds (<b>1</b>–<b>4</b> and <b>6</b>–<b>8</b>) inhibited SARS-CoV PLpro activity in a dose-dependent manner, with their <i>K</i><sub>i</sub>s ranging from 5.56 to 75.37 μM. The structure–activity analysis of pterocarpans (<b>1</b>–<b>6</b>) showed that activity was enhanced by C1-OCH<sub>3</sub>, but it was reduced by C8-CH<sub>3</sub>. 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.
ISSN:2223-7747