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ID: ALA4699479

Journal: Bioorg Med Chem Lett

Title: Structure-aided optimization of 3-O-β-chacotriosyl epiursolic acid derivatives as novel H5N1 virus entry inhibitors.

Authors: Li S,Jia X,Li H,Ye Y,Zhang X,Gao Y,Guo G,Liu S,Song G

Abstract: It is urgent to develop new antiviral agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene saponins with 3-O-β-chacotriosyl residue are novel H5N1 virus entry inhibitors. In the present study, a series of C-28 modified 3-O-β-chacotriosyl epiursolic acid derivatives via conjugation with different kinds of sides were synthesized, of which anti-H5N1 activities in A549 cells were evaluated in vitro. Among them, 10 exhibited strongest anti-H5N1 potency at the low-micromole level without cytotoxicity, surpassing the potency of ribavirin. Further mechanism studies of the lead compound 10 based on HI, SPR and molecular modeling revealed that these new 3-epiursolic acid saponins could bind tightly to the viral envelope HA protein, thus blocking the invasion of H5N1 viruses into host cells.

CiteXplore: 32882419

DOI: 10.1016/j.bmcl.2020.127518