Enhanced Inhibition of Influenza A Virus Adhesion by Di- and Trivalent Hemagglutinin Inhibitors.


Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
11 07 2019
Historique:
pubmed: 30 6 2019
medline: 23 6 2020
entrez: 29 6 2019
Statut: ppublish

Résumé

Multivalent carbohydrate-based ligands were synthesized and evaluated as inhibitors of the adhesion protein HA of the influenza A virus (IAV). HA relies on multivalency for strong viral adhesion. While viral adhesion inhibition by large polymeric molecules has proven viable, limited success was reached for smaller multivalent compounds. By linking of sialylated LAcNAc units to di- and trivalent scaffolds, inhibitors were obtained with an up to 428-fold enhanced inhibition in various assays.

Identifiants

pubmed: 31251606
doi: 10.1021/acs.jmedchem.9b00303
pmc: PMC6627469
doi:

Substances chimiques

Antiviral Agents 0
Glycoconjugates 0
Hemagglutinin Glycoproteins, Influenza Virus 0
Ligands 0
Sialic Acids 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6398-6404

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Auteurs

Wenjing Lu (W)

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , P.O. Box 80082, NL-3508 TB Utrecht , The Netherlands.

Wenjuan Du (W)

Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine , Utrecht University , NL-3584 CL Utrecht , The Netherlands.

Victor J Somovilla (VJ)

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , P.O. Box 80082, NL-3508 TB Utrecht , The Netherlands.

Guangyun Yu (G)

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , P.O. Box 80082, NL-3508 TB Utrecht , The Netherlands.

Diksha Haksar (D)

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , P.O. Box 80082, NL-3508 TB Utrecht , The Netherlands.

Erik de Vries (E)

Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine , Utrecht University , NL-3584 CL Utrecht , The Netherlands.

Geert-Jan Boons (GJ)

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , P.O. Box 80082, NL-3508 TB Utrecht , The Netherlands.

Robert P de Vries (RP)

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , P.O. Box 80082, NL-3508 TB Utrecht , The Netherlands.

Cornelis A M de Haan (CAM)

Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine , Utrecht University , NL-3584 CL Utrecht , The Netherlands.

Roland J Pieters (RJ)

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , P.O. Box 80082, NL-3508 TB Utrecht , The Netherlands.

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Classifications MeSH