Synthesis and structure-activity relationship study of saponin-based membrane fusion inhibitors against SARS-CoV-2.
Bioorg Chem
; 127: 105985, 2022 10.
Article
in English
| MEDLINE | ID: covidwho-1906793
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 (â3)-ß-d-Xyl-(1 â 4)-α-l-Rham-(1 â 2)-ß-d-Ara-(1 â ) 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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Saponins
/
COVID-19
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Bioorg Chem
Year:
2022
Document Type:
Article
Affiliation country:
J.bioorg.2022.105985
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