Li Bin, Qiao Liansheng, Zhang Jianuo, Xiao Qi, 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.
J Tradit Complement Med. 2024 Jan 16;14(5):501-509. doi: 10.1016/j.jtcme.2024.01.005. eCollection 2024 Sep.
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), turned into a global pandemic, and there remains an urgent demand for specific/targeted drugs for the disease. The 3C-like protease (3CL) is a promising target for developing anti-coronavirus drugs. fruit is a well-known traditional Chinese medicine (TCM) with good antiviral activity. This study found that the ethanolic extract displayed a significant inhibitory effect against SARS-CoV-2 3CL. Forty-four compounds were identified in this extract using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Combining molecular docking and experiments, we found that two epimeric 7,8-secolignans, rel-(1,2)-1-(3,4-dimethoxyphenyl)-2-methyl-3-oxobutyl-3,4-dimethoxybenzoate () and rel-(1,2)-1-(3,4-dimethoxyphenyl)-2-methyl-3-oxobutyl-3,4-dimethoxybenzoate (, potently inhibited 3CL with IC values of 4.88 ± 0.60 μM and 4.75 ± 0.34 μM, respectively. Moreover, and experiments indicated that compounds and were potent in regulating the inflammatory response and preventing lung injury. Our findings indicate that compounds and may emerge as promising SARS-CoV-2 inhibitors via 3CL inhibition and anti-inflammatory mechanisms.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）已演变成全球大流行，对该疾病的特异性/靶向药物仍有迫切需求。3C样蛋白酶（3CL）是开发抗冠状病毒药物的一个有前景的靶点。某果实是一种具有良好抗病毒活性的著名传统中药。本研究发现，该果实的乙醇提取物对SARS-CoV-2 3CL显示出显著的抑制作用。使用超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF/MS）在该提取物中鉴定出44种化合物。结合分子对接和实验，我们发现两种差向异构的7,8-裂环木脂素，rel-(1,2)-1-(3,4-二甲氧基苯基)-2-甲基-3-氧代丁基-3,4-二甲氧基苯甲酸酯（）和rel-(1,2)-1-(3,4-二甲氧基苯基)-2-甲基-3-氧代丁基-3,4-二甲氧基苯甲酸酯（，分别以4.88±0.60μM和4.75±0.34μM的IC值有效抑制3CL。此外，和实验表明，化合物和在调节炎症反应和预防肺损伤方面具有效力。我们的研究结果表明，化合物和可能通过抑制3CL和抗炎机制成为有前景的SARS-CoV-2抑制剂。
