Dual-action heteromultivalent glycopolymers stringently block and arrest influenza A virus infection in vitro and ex vivo
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Here, we demonstrate the concerted inhibition of different influenza A virus (IAV) strains using a low-molecular-weight dual-action linear polymer. The 6'-sialyllactose and zanamivir conjugates of linear polyglycerol are optimized for simultaneous targeting of hemagglutinin and neuraminidase on the IAV surface. Independent of IAV subtypes, hemagglutination inhibition data suggest better adsorption of the heteromultivalent polymer than homomultivalent analogs onto the virus surface. Cryo-TEM images imply heteromultivalent compound-mediated virus aggregation. The optimized polymeric nanomaterial inhibits >99.9% propagation of various IAV strains 24 h postinfection in vitro at low nM concentrations and is up to 10000× more effective than the commercial zanamivir drug. In a human lung ex vivo multicyclic infection setup, the heteromultivalent polymer outperforms the commercial drug zanamivir and homomultivalent analogs or their physical mixtures. This study authenticates the translational potential of the dual-action targeting approach using small polymers for broad and high antiviral efficacy.
Date Issued
2023-06-14
Date Acceptance
2023-05-01
Citation
Nano Letters: a journal dedicated to nanoscience and nanotechnology, 2023, 23 (11), pp.4844-4853
ISSN
1530-6984
Publisher
American Chemical Society
Start Page
4844
End Page
4853
Journal / Book Title
Nano Letters: a journal dedicated to nanoscience and nanotechnology
Volume
23
Issue
11
Copyright Statement
Copyright © 2023 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Nano Lett., after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.nanolett.3c00408
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37220024
Subjects
broad inhibition
dual-action linear polymer
glycopolymer
heteromultivalency
influenza A virus
multicyclic infection
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2023-05-23