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 (K_D) 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.

中文翻译：

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两种白藜芦醇低聚物抑制组织蛋白酶 L 活性以抑制 SARS-CoV-2 进入

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，这是预防和治疗病毒感染的关键靶点。在此，我们描述了 miyabenol C 和 trans-ε-viniferin，这两种白藜芦醇寡聚物通过靶向宿主蛋白酶组织蛋白酶 L 特异性抑制 SARS-CoV-2 进入。使用了几种基于细胞的测定来证明白藜芦醇寡聚物的作用及其靶点是通过筛选抗病毒靶标来确定的。分子对接分析表明寡聚体可以占据组织蛋白酶L的活性空腔。表面等离振子共振分析表明miyabenol C-cathepsin L和trans-ε-viniferin-cathepsin L的平衡解离常数（ K _D ）值为5.54和分别为 8.54 μM，表明它们对组织蛋白酶 L 具有出色的结合能力。我们的研究证明了白藜芦醇寡聚物作为先导化合物在通过靶向组织蛋白酶 L 控制 SARS-CoV-2 感染方面的潜在应用。