Triterpenoidal Saponins from the Leaves of Aster koraiensis Offer Inhibitory Activities against SARS-CoV-2.

Triterpenoidal saponins have been reported to be able to restrain SARS-CoV-2 infection. To isolate antiviral compounds against SARS-CoV-2 from the leaves of Aster koraiensis , we conducted multiple steps of column chromatography. We isolated six triperpenoidal saponins from A . koraiensis leaves, including three unreported saponins. Their chemical structures were determined using HR-MS and NMR data analyses. Subsequently, we tested the isolates to assess their ability to impede the entry of the SARS-CoV-2 pseudovirus (pSARS-CoV-2) into ACE2 + H1299 cells and found that five of the six isolates displayed antiviral activity with an IC 50 value below 10 μM. Notably, one unreported saponin, astersaponin J ( 1 ), blocks pSARS-CoV-2 in ACE2 + and ACE2/TMPRSS2 + cells with similar IC 50 values (2.92 and 2.96 μM, respectively), without any significant toxic effect. Furthermore, our cell-to-cell fusion and SARS-CoV-2 Spike-ACE2 binding assays revealed that astersaponin J inhibits membrane fusion, thereby blocking both entry pathways of SARS-CoV-2 while leaving the interaction between the SARS-CoV-2 Spike and ACE2 unaffected. Overall, this study expands the list of antiviral saponins by introducing previously undescribed triterpenoidal saponins isolated from the leaves of A. koraiensis , thereby corroborating the potency of triterpenoid saponins in impeding SARS-CoV-2 infection.