Laboratory of Pharmacognocy, School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1, Keyakidai, Sakado, Saitama, 350-0295, Japan.
Laboratory of Natural Products and Phytochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1, Keyakidai, Sakado, Saitama, 350-0295, Japan.
J Nat Med. 2021 Sep;75(4):1080-1085. doi: 10.1007/s11418-021-01519-9. Epub 2021 Apr 30.
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains a cleavage motif R-X-X-R for furin-like enzymes at the boundary of the S1/S2 subunits. The cleavage of the site by cellular proteases is essential for S protein activation and virus entry. We screened the inhibitory effects of crude drugs on in vitro furin-like enzymatic activities using a fluorogenic substrate with whole-cell lysates. Of the 124 crude drugs listed in the Japanese Pharmacopeia, aqueous ethanolic extract of Cnidii Monnieris Fructus, which is the dried fruit of Cnidium monnieri Cussion, significantly inhibited the furin-like enzymatic activities. We further fractionated the plant extract and isolated the two active compounds with the inhibitory activity, namely, imperatorin and osthole, whose IC values were 1.45 mM and 9.45 µM, respectively. Our results indicated that Cnidii Monnieris Fructus might exert inhibitory effects on furin-like enzymatic activities, and that imperatorin and osthole of the crude drug could be potential inhibitors of the motif cleavage.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的刺突（S）蛋白在 S1/S2 亚基交界处含有一个弗林样酶的裂解基序 R-X-X-R。该位点被细胞蛋白酶切割对于 S 蛋白的激活和病毒进入至关重要。我们使用全细胞裂解物的荧光底物筛选了 124 种日本药典中列出的粗提药物对体外弗林样酶活性的抑制作用。在日本药典中列出的 124 种粗制剂中，蛇床子的水醇提取物（蛇床子的干燥果实）显著抑制了弗林样酶的活性。我们进一步对植物提取物进行了分级分离，并分离出具有抑制活性的两种活性化合物，即欧前胡素和蛇床子素，其 IC 值分别为 1.45mM 和 9.45µM。我们的结果表明，蛇床子可能对弗林样酶活性具有抑制作用，而该粗制剂中的欧前胡素和蛇床子素可能是该基序切割的潜在抑制剂。
