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Eur J Med Chem. 2017 Apr 2;134:133-139. doi: 10.1016/j.ejmech.2017.03.087. [Epub ahead of print]
Inhibition of influenza virus infection by multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin conjugates.
Tian Z1, Si L1, Meng K1, Zhou X1, Zhang Y2, Zhou D1, Xiao S3.
Author information
Abstract
Multivalent ligands that exhibit high binding affinity to influenza hemagglutinin (HA) trimer can block the interaction of HA with its sialic acid receptor. In this study, a series of multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin (CD) derivatives were designed and synthesized using 1, 3-dipolar cycloaddition click reaction. A cell-based assay showed that three compounds (25, 28 and 31) exhibited strong inhibitory activity against influenza A/WSN/33 (H1N1) virus. Compound 28 showed the most potent anti-influenza activity with IC50 of 4.7 μM. The time-of-addition assay indicated that compound 28 inhibited the entry of influenza virus into host cell. Further hemagglutination inhibition (HI) and surface plasmon resonance (SPR) assays indicated that compound 28 tightly bound to influenza HA protein with a dissociation constant (KD) of 4.0 μM. Our results demonstrated a strategy of using per-O-methylated β-CD as a scaffold for designing multivalent compounds to disrupt influenza HA protein-host receptor protein interaction and thus block influenza virus entry into host cells.
Copyright ? 2017 Elsevier Masson SAS. All rights reserved.
KEYWORDS:
Hemagglutinin; Influenza virus; Multivalent effect; Pentacyclic triterpene; Per-O-methylated cyclodextrin
PMID: 28411453 DOI: 10.1016/j.ejmech.2017.03.087
Inhibition of influenza virus infection by multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin conjugates.
Tian Z1, Si L1, Meng K1, Zhou X1, Zhang Y2, Zhou D1, Xiao S3.
Author information
Abstract
Multivalent ligands that exhibit high binding affinity to influenza hemagglutinin (HA) trimer can block the interaction of HA with its sialic acid receptor. In this study, a series of multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin (CD) derivatives were designed and synthesized using 1, 3-dipolar cycloaddition click reaction. A cell-based assay showed that three compounds (25, 28 and 31) exhibited strong inhibitory activity against influenza A/WSN/33 (H1N1) virus. Compound 28 showed the most potent anti-influenza activity with IC50 of 4.7 μM. The time-of-addition assay indicated that compound 28 inhibited the entry of influenza virus into host cell. Further hemagglutination inhibition (HI) and surface plasmon resonance (SPR) assays indicated that compound 28 tightly bound to influenza HA protein with a dissociation constant (KD) of 4.0 μM. Our results demonstrated a strategy of using per-O-methylated β-CD as a scaffold for designing multivalent compounds to disrupt influenza HA protein-host receptor protein interaction and thus block influenza virus entry into host cells.
Copyright ? 2017 Elsevier Masson SAS. All rights reserved.
KEYWORDS:
Hemagglutinin; Influenza virus; Multivalent effect; Pentacyclic triterpene; Per-O-methylated cyclodextrin
PMID: 28411453 DOI: 10.1016/j.ejmech.2017.03.087