Woo Hyun Sim, Lee Kon Ho, Park Ki Hun, Kim Dae Wook
Forest Bioresources Department, Baekdudaegan National Arboretum, Bonghwa-gun 36209, Republic of Korea.
Department of Microbiology, School of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea.
Plants (Basel). 2024 Nov 26;13(23):3319. doi: 10.3390/plants13233319.
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.
尽管由严重急性呼吸综合征冠状病毒（SARS-CoV）引发的冠状病毒疾病爆发如今臭名昭著，但这种病毒仍然对全球人口构成威胁。尽管针对SARS-CoV已经展开了大量研究工作，但尚未有关于靶向其关键酶之一木瓜样蛋白酶（PLpro）的天然小分子的报道。在本研究中，从[植物名称]的根皮中分离出了九种具有SARS-CoV PLpro抑制活性的黄酮类化合物。这些化合物被鉴定为刺桐素II（）、莱氏木素G4（）、1-甲氧基刺桐素II（）、双色豆素A（）、双色豆素B（）、双色豆素（）、黄当归醇（）、（±）-莱氏醇（）和小叶黄酮（）。大多数化合物（[具体化合物]和[具体化合物]）以剂量依赖方式抑制SARS-CoV PLpro活性，其半数抑制浓度范围为5.56至75.37μM。紫檀烷类化合物（[具体化合物]）的构效分析表明，C1-OCH可增强活性，但C8-CH会降低活性。机理分析显示所有抑制剂均为非竞争性。本研究中分离出的一些关键化合物是紫檀烷类，它们在豆科植物中大量存在。总体而言，本研究鉴定出了丰富的SARS-CoV木瓜样蛋白酶抑制剂来源。
