2. Academic Validation
  3. Structure-aided optimization of 3-O-β-chacotriosyl epiursolic acid derivatives as novel H5N1 virus entry inhibitors

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

  • Bioorg Med Chem Lett. 2020 Nov 15;30(22):127518. doi: 10.1016/j.bmcl.2020.127518.
Sumei Li 1,  Xiuhua Jia 2,  Hui Li 3,  Yilu Ye 4,  Xuesha Zhang 3,  Yongfeng Gao 3,  Guoqing Guo 1,  Shuwen Liu 5,  Gaopeng Song 6
Affiliations

Affiliations

  • 1 Department of Human Anatomy, School of Medicine, Jinan University, Guangzhou 510632, China.
  • 2 Department of Ophthalmology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
  • 3 College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China.
  • 4 School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • 5 School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 6 College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China. Electronic address: [email protected].
PMID: 32882419 DOI: 10.1016/j.bmcl.2020.127518
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.

Keywords

3-Epiursolic acid saponins; H5N1 entry inhibitors; Semi-synthesis; Structure–activity relationships.

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