School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
J Nat Prod. 2023 Jun 23;86(6):1428-1436. doi: 10.1021/acs.jnatprod.3c00104. Epub 2023 Jun 2.
Traditional herbal medicine offers opportunities to discover novel therapeutics against SARS-CoV-2 mutation. The dried aerial part of mint ( L.) was chosen for bioactivity-guided extraction. Seven constituents were isolated and characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). Syringic acid and methyl rosmarinate were evaluated in drug combination treatment. Ten amide derivatives of methyl rosmarinate were synthesized, and the dodecyl () and 3-ethylphenyl () derivatives demonstrated significant improvement in the anti-SARS-CoV-2 plaque reduction assay, achieving IC of 0.77 and 2.70 μM, respectively, against Omicron BA.1 as compared to methyl rosmarinate's IC of 57.0 μM. Spike protein binding and 3CL inhibition assays were performed to explore the viral inhibition mechanism. Molecular docking of compounds and to 3CL was performed to reveal potential interaction. In summary, natural products with anti-Omicron BA.1 activity were isolated from and derivatives of methyl rosmarinate were synthesized, showing 21- to 74-fold improvement in antiviral activity against Omicron BA.1.
传统草药为发现针对 SARS-CoV-2 突变的新型治疗方法提供了机会。薄荷（L.）的干燥地上部分被选为基于生物活性的提取部位。通过核磁共振（NMR）和质谱（MS）分离和鉴定了 7 种成分。评估了丁香酸和甲基迷迭香酸在药物联合治疗中的作用。合成了 10 种甲基迷迭香酸的酰胺衍生物，其中十二烷基（）和 3-乙基苯基（）衍生物在抗 SARS-CoV-2 噬斑减少测定中表现出显著改善，对奥密克戎 BA.1 的 IC 分别为 0.77 和 2.70 μM，而甲基迷迭香酸的 IC 为 57.0 μM。进行了刺突蛋白结合和 3CL 抑制测定，以探索病毒抑制机制。对化合物和对 3CL 的分子对接揭示了潜在的相互作用。总之，从薄荷中分离出具有抗奥密克戎 BA.1 活性的天然产物，并合成了甲基迷迭香酸的衍生物，对奥密克戎 BA.1 的抗病毒活性提高了 21-74 倍。
