Department of Chemistry, Korea Advanced Institute of Science & Technology (KAIST), Daejeon 34141, South Korea.
Center for Cognition and Sociality, Cognitive Glioscience Group, Institute for Basic Science, Daejeon 34126, Republic of Korea.
Bioorg Chem. 2022 Oct;127:105985. doi: 10.1016/j.bioorg.2022.105985. Epub 2022 Jun 26.
We previously discovered that triterpenoid saponin platycodin D inhibits the SARS-CoV-2 entry to the host cell. Herein, we synthesized various saponin derivatives and established a structure-activity relationship of saponin-based antiviral agents against SARS-CoV-2. We discovered that the C3-glucose, the C28-oligosaccharide moiety that consist of (→3)-β-d-Xyl-(1 → 4)-α-l-Rham-(1 → 2)-β-d-Ara-(1 → ) as the last three sugar units, and the C16-hydroxyl group were critical components of saponin-based coronavirus cell entry inhibitors. These findings enabled us to develop minimal saponin-based antiviral agents that are equipotent to the originally discovered platycodin D. We found that our saponin-based antiviral agents inhibited both the endosomal and transmembrane protease serine 2-mediated cell surface viral entries. Cell fusion assay experiment revealed that our newly developed compounds inhibit the SARS-CoV-2 entry by blocking the fusion between the viral and host cell membranes. The effectiveness of the newly developed antiviral agents over various SARS-CoV-2 variants hints at the broad-spectrum antiviral efficacy of saponin-based therapeutics against future coronavirus variants.
我们之前发现三萜皂苷元远志酸 D 可抑制 SARS-CoV-2 进入宿主细胞。在此，我们合成了各种皂苷衍生物，并建立了基于皂苷的抗 SARS-CoV-2 病毒药物的构效关系。我们发现 C3-葡萄糖、由 (→3)-β-d-Xyl-(1 → 4)-α-l-Rham-(1 → 2)-β-d-Ara-(1 → )组成的 C28-寡糖部分作为最后三个糖单元，以及 C16-羟基是基于皂苷的冠状病毒细胞进入抑制剂的关键组成部分。这些发现使我们能够开发出与最初发现的远志酸 D 等效的最小基于皂苷的抗病毒药物。我们发现，我们基于皂苷的抗病毒药物可抑制内体和跨膜蛋白酶丝氨酸 2 介导的细胞表面病毒进入。细胞融合实验表明，我们新开发的化合物通过阻断病毒和宿主细胞膜之间的融合来抑制 SARS-CoV-2 的进入。新开发的抗病毒药物对各种 SARS-CoV-2 变体的有效性表明，基于皂苷的疗法对未来冠状病毒变体具有广谱抗病毒功效。
