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Inhibition of Influenza Virus Infection by Multivalent Pentacyclic Triterpene-Functionalized per- O -Methylated Cyclodextrin Conjugates
- Source :
- European Journal of Medicinal Chemistry, European Journal of Medicinal Chemistry, 2017, 134, pp.133--139. ⟨10.1016/j.ejmech.2017.03.087⟩, European Journal of Medicinal Chemistry, Elsevier, 2017, 134, pp.133--139. ⟨10.1016/j.ejmech.2017.03.087⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
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.
- Subjects :
- 0301 basic medicine
POLE 3
Hemagglutinin (influenza)
Hemagglutinin Glycoproteins, Influenza Virus
010402 general chemistry
01 natural sciences
Antiviral Agents
Virus
Madin Darby Canine Kidney Cells
03 medical and health sciences
chemistry.chemical_compound
Dogs
Influenza A Virus, H1N1 Subtype
Orthomyxoviridae Infections
Viral entry
Drug Discovery
Influenza, Human
Animals
Humans
[CHIM]Chemical Sciences
IC50
Pharmacology
chemistry.chemical_classification
Cyclodextrins
Hemagglutination assay
Cyclodextrin
biology
Chemistry
Organic Chemistry
General Medicine
Virus Internalization
0104 chemical sciences
3. Good health
Sialic acid
Dissociation constant
GOBS
030104 developmental biology
Biochemistry
biology.protein
Pentacyclic Triterpenes
Subjects
Details
- Language :
- English
- ISSN :
- 02235234 and 17683254
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry, European Journal of Medicinal Chemistry, 2017, 134, pp.133--139. ⟨10.1016/j.ejmech.2017.03.087⟩, European Journal of Medicinal Chemistry, Elsevier, 2017, 134, pp.133--139. ⟨10.1016/j.ejmech.2017.03.087⟩
- Accession number :
- edsair.doi.dedup.....9b4240b5b03c093860cef7cdf1b7c298