Mucin-Inspired, High Molecular Weight Virus Binding Inhibitors Show Biphasic Binding Behavior to Influenza A Viruses.
Animals
Antiviral Agents
/ pharmacology
Cell Membrane
/ metabolism
Dogs
Glycerol
/ chemical synthesis
Hemagglutinins, Viral
/ metabolism
Influenza A virus
/ drug effects
Madin Darby Canine Kidney Cells
Molecular Weight
Mucins
/ chemistry
Neuraminidase
/ metabolism
Polymers
/ chemical synthesis
Virus Attachment
/ drug effects
TIRF microscopy
hyperbranched polyglycerol
influenza A viruses
single particle tracking
virus binding inhibition
Journal
Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
30
07
2020
revised:
28
09
2020
pubmed:
3
11
2020
medline:
4
5
2021
entrez:
2
11
2020
Statut:
ppublish
Résumé
Multivalent binding inhibitors are a promising new class of antivirals that prevent virus infections by inhibiting virus binding to cell membranes. The design of these inhibitors is challenging as many properties, for example, inhibitor size and functionalization with virus attachment factors, strongly influence the inhibition efficiency. Here, virus binding inhibitors are synthesized, the size and functionalization of which are inspired by mucins, which are naturally occurring glycosylated proteins with high molecular weight (MDa range) and interact efficiently with various viruses. Hyperbranched polyglycerols (hPGs) with molecular weights ranging between 10 and 2600 kDa are synthesized, thereby hitting the size of mucins and allowing for determining the impact of inhibitor size on the inhibition efficiency. The hPGs are functionalized with sialic acids and sulfates, as suggested from the structure of mucins, and their inhibition efficiency is determined by probing the inhibition of influenza A virus (IAV) binding to membranes using various methods. The largest, mucin-sized inhibitor shows potent inhibition at pm concentrations, while the inhibition efficiency decreases with decreasing the molecular weight. Interestingly, the concentration-dependent IAV inhibition shows a biphasic behavior, which is attributed to differences in the binding affinity of the inhibitors to the two IAV envelope proteins, neuraminidase, and hemagglutinin.
Identifiants
pubmed: 33135314
doi: 10.1002/smll.202004635
doi:
Substances chimiques
Antiviral Agents
0
Hemagglutinins, Viral
0
Mucins
0
Polymers
0
polyglycerol
25618-55-7
Neuraminidase
EC 3.2.1.18
Glycerol
PDC6A3C0OX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2004635Informations de copyright
© 2020 The Authors. Published by Wiley-VCH GmbH.
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