Abstract
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.
Keywords: COVID-19; Complex molecules synthesis; Membrane fusion; SARS-CoV-2; Saponins.
【저자키워드】 COVID-19, SARS-CoV-2, membrane fusion, Complex molecules synthesis, Saponins., 【초록키워드】 coronavirus, SARS-CoV-2 variant, protease, inhibitors, SARS-CoV-2 variants, Antiviral agents, Cell fusion, Effectiveness, antiviral efficacy, membrane fusion, experiment, antiviral agent, fusion, Critical, Glucose, coronavirus variants, sugar, host cell, Saponin, Serine, SARS-CoV-2 entry, Compound, cell entry, transmembrane, component, derivative, host cell membranes, saponins, Cell, endosomal, develop, inhibit, inhibited, Complex molecule, the SARS-CoV-2, 【제목키워드】 inhibitor, synthesis,