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Synthesis and structure-activity relationship study of saponin-based membrane fusion inhibitors against SARS-CoV-2.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2022 Oct; Vol. 127, pp. 105985. Date of Electronic Publication: 2022 Jun 26. - Publication Year :
- 2022
-
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.<br /> (Copyright © 2022 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 127
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 35809512
- Full Text :
- https://doi.org/10.1016/j.bioorg.2022.105985