Li Bin, Qiao Liansheng, Xiao Qi, Zhang Jianuo, Liu Jiushi, Zhang Bengang, Liu Haitao
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, 100193, Beijing China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, 100029, Beijing, China.
Phytomed Plus. 2023 May;3(2):100432. doi: 10.1016/j.phyplu.2023.100432. Epub 2023 Mar 11.
fruit is a well-known traditional Chinese medicine (TCM), whose extract has a potent inhibitory effect on the severe acute respiratory syndrome-coronavirus-2 (SARS‑CoV‑2) 3-chymotrypsin-like protease (3CL) and papain-like protease (PL).
This work aims to find the active components from the fruit of against SARS‑CoV‑2 3CL and PL.
The chemical constituents of the fruit of were retrieved based on the electronic databases, such as Web of Science, PubMed, Medline Plus, and CNKI. Molecular docking was used to screen the active components against SARS‑CoV‑2 3CL and PL. Potential hit compounds were further evaluated by enzymatic activity assay. Furthermore, the anti-inflammatory activities of the active compounds were further explored using the phorbol-12-myristate-13-acetate (PMA)-induced THP1 cells model.
In this work, we retrieved 75 components of fruit, including 62 dibenzocyclooctadiene-type lignans, 3 diarylbutane-type lignans, 2 tetrahydrofuran-type lignans, and 8 nortriterpenoids. Combining molecular docking study and experiments, we found that pregomisin (), meso‑dihydroguaiaretic acid (), and nordihydroguaiaretic acid () could potently inhibit 3CL with IC values of 3.07 ± 0.38, 4.12 ± 0.38, and 6.06 ± 0.62 μM, respectively, and inhibit PL with IC values of 5.23 ± 0.33, 4.24 ± 0.46, and 16.28 ± 0.54 μM, respectively. Interestingly, compounds , and also have potent activities of regulating the inflammatory response .
Our results suggest that compounds , and may be promising SARS-CoV-2 3CL and PL inhibitors and anti-inflammatory.
[某种果实名称]是一种著名的传统中药，其提取物对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的3-糜蛋白酶样蛋白酶（3CL）和木瓜蛋白酶样蛋白酶（PL）具有强大的抑制作用。
本研究旨在从[某种果实名称]果实中寻找抗SARS-CoV-2 3CL和PL的活性成分。
基于Web of Science、PubMed、Medline Plus和CNKI等电子数据库检索[某种果实名称]果实的化学成分。采用分子对接技术筛选抗SARS-CoV-2 3CL和PL的活性成分。通过酶活性测定进一步评估潜在的命中化合物。此外，使用佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）诱导的THP1细胞模型进一步探究活性化合物的抗炎活性。
在本研究中，我们检索到[某种果实名称]果实的75种成分，包括62种二苯并环辛二烯型木脂素、3种二芳基丁烷型木脂素、2种四氢呋喃型木脂素和8种降三萜类化合物。结合分子对接研究和[具体实验名称]实验，我们发现前戈米辛（[化合物名称1]）、中-二氢愈创木酸（[化合物名称2]）和去甲二氢愈创木酸（[化合物名称3]）能够有效抑制3CL，IC50值分别为3.07±0.38、4.12±0.38和6.06±0.62μM，抑制PL的IC50值分别为5.23±0.33、4.24±0.46和16.28±0.54μM。有趣的是，化合物[化合物名称1]、[化合物名称2]和[化合物名称3]还具有强大的调节炎症反应的活性。
我们的结果表明，化合物[化合物名称1]、[化合物名称2]和[化合物名称3]可能是有前景的SARS-CoV-2 3CL和PL抑制剂以及抗炎剂。
