期刊
MOLECULAR PHARMACEUTICS
卷 17, 期 7, 页码 2546-2554出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.0c00244
关键词
betulinic acid; alpha-cyclodextrin; influenza virus; entry inhibitor
资金
- National Natural Science Foundation of China [21877007, 91753202, 81530090, 21702007]
- State Key Laboratory of Phytochemistry and Plant Resources in West China
Naturally occurring pentacyclic triterpenes, such as betulinic acid (BA) and its derivatives, exhibit various pharmaceutical activities and have been the subject of great interest, in particular for their antiviral properties. Here, we found a new anti-influenza virus conjugate, hexakis 6- deoxy-6- [4-N-(3 beta-hydroxy-lup-20 (29) -en -28-oate) aminomethyl- 1H-1, 2,3-triazol-1-yl] -2,3-di-O-acetyl-alpha-cyclodextrin (CYY1-11, 1), in a mini library of pentacyclic triterpene-cyclodextrin conjugates by performing a cell-based screening assay and then exploring the underlying mechanisms. Our results showed that conjugate 1 possessed a high-level activity against the influenza virus A/WSN/33 with an IC(50 )value of 5.20 mu M (SI > 38.4). The study of the mechanism of action indicated that conjugate 1 inhibited viral replication by directly targeting the influenza hemagglutinin protein (K-D = 1.50 mu M), thus efficiently preventing the attachment of the virion to its receptors on host cells and subsequent infection. This study suggests that multivalent BA derivatives have possible use as a new class of influenza virus entry inhibitors.
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