Lewis-X-Containing Triterpenoid Saponins Inhibit DC-SIGN- and L-SIGN-Mediated Transfer of HIV-1 Infection

Marin, Oscar Javier Gamboa; Ng, Kurtis; Verma, Nitish; Flavien Yapi, Assi Gérard; Pantophlet, Ralph et Gauthier, Charles ORCID: https://orcid.org/0000-0002-2475-2050 (2025). Lewis-X-Containing Triterpenoid Saponins Inhibit DC-SIGN- and L-SIGN-Mediated Transfer of HIV-1 Infection Chemistry , vol. 31 , nº 32. pp. 1-8. DOI: 10.1002/chem.202500993.

Prévisualisation

PDF - Version publiée Disponible sous licence Creative Commons Attribution Non-commercial. Télécharger (1MB) | Prévisualisation

Résumé

Blocking DC-SIGN- and L-SIGN-mediated HIV-1 attachment to immune cells represents a promising strategy for developing antiretroviral agents effective during the early stages of sexual transmission. Although mannose- and fucose-based ligands have received considerable attention, Lewis-based inhibitors remain relatively underexplored. In this study, we report the first synthesis of Lewis-X-containing triterpenoid saponins featuring betulinic acid and echinocystic acid as aglycones. These saponins were stereoselectively and efficiently synthesized in six linear steps using a convergent approach that leveraged thioglycoside and trichloroacetimidate glycosylation chemistries. Notably, our findings demonstrate that these Lewis-X-containing triterpenoid saponins are among the most potent monovalent inhibitors reported to date of DC-SIGN- and L-SIGN-mediated transfer of HIV-1 infection to CD4-positive cells, with IC50 values in the low micromolar range (21-50 mM). This work lays a valuable foundation for the development of saponin-based antiviral agents targeting immune cells.

Type de document:	Article
Informations complémentaires:	document e202500993 This work was supported by funds from a Natural Sciences and Engineering Research Council of Canada (NSERC) Discov- ery grant (RGPIN-2022-04515, to C. G.), a Fonds de recherche du Québec – Nature et technologies (FRQNT) Team grant (2021-PR- 283932, to C. G.), an NSERC-FRQNT Team Research supplement– Alliance grant (ALLRP 560901–20, to C. G. and R. P.), and a National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) grant (R01AI134229 to R. P.). C. G. was supported by a Fonds de recherche du Québec – Santé (FRQS) Research Scholars Senior Career Award. O. J. G. M. thanks FRQNT and the Armand-Frappier Foundation for Ph.D. scholar- ships. A. G. F. Y. thanks the Armand-Frappier Foundation for an undergraduate scholarship
Mots-clés libres:	DC-SIGN; HIV-1; L-SIGN; Lewis-X; triterpenoid saponins
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	07 juill. 2025 18:55
Dernière modification:	07 juill. 2025 18:55
URI:	https://espace.inrs.ca/id/eprint/16498

Gestion Actions (Identification requise)

Modifier la notice