Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China.
State Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China.
J Agric Food Chem. 2023 Apr 12;71(14):5535-5546. doi: 10.1021/acs.jafc.2c07811. Epub 2023 Mar 30.
Cell entry of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) depends on specific host cell proteases, which are the key targets for preventing and treating viral infections. Herein, we describe miyabenol C and trans-ε-viniferin, two resveratrol oligomers that specifically inhibit SARS-CoV-2 entry by targeting host protease cathepsin L. Several cell-based assays were used to demonstrate the effect of resveratrol oligomers, and their target was identified via screening of antiviral targets. Molecular docking analysis suggested that the oligomers could occupy the active cavity of cathepsin L. The surface plasmon resonance assay showed that the equilibrium dissociation constant () values of miyabenol C-cathepsin L and trans-ε-viniferin-cathepsin L were 5.54 and 8.54 μM, respectively, indicating their excellent binding ability for cathepsin L. Our study demonstrated the potential application of resveratrol oligomers as lead compounds in controlling SARS-CoV-2 infection by targeting cathepsin L.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的细胞进入依赖于特定的宿主细胞蛋白酶，这些蛋白酶是预防和治疗病毒感染的关键靶点。本文描述了米雅贝醇 C 和反式-ε-白藜芦醇二聚体，这两种白藜芦醇二聚体通过靶向宿主蛋白酶组织蛋白酶 L 特异性抑制 SARS-CoV-2 的进入。使用多种基于细胞的测定法来证明白藜芦醇二聚体的作用，并且通过抗病毒靶标筛选鉴定了其靶标。分子对接分析表明，这些二聚体可以占据组织蛋白酶 L 的活性腔。表面等离子体共振分析表明，米雅贝醇 C-组织蛋白酶 L 和反式-ε-白藜芦醇二聚体-组织蛋白酶 L 的平衡解离常数（）值分别为 5.54 和 8.54 μM，表明它们对组织蛋白酶 L 具有出色的结合能力。我们的研究表明，白藜芦醇二聚体作为通过靶向组织蛋白酶 L 控制 SARS-CoV-2 感染的先导化合物具有潜在的应用前景。
