Journal article 151 views
Evaluation of Multivalent Sialylated Polyglycerols for Resistance Induction in and Broad Antiviral Activity against Influenza A Viruses
,
Pallavi Kiran,
Malte Hilsch,
Valentin Reiter-Scherer,
Lutz Adam,
Badri Parshad,
Matthias Budt,
Simon Klenk,
Katrin Sellrie,
Daniel Lauster,
Peter H. Seeberger,
Christian P. R. Hackenberger,
Andreas Herrmann,
Rainer Haag ,
Thorsten Wolff
Journal of Medicinal Chemistry, Volume: 64, Issue: 17, Pages: 12774 - 12789
Swansea University Author:
Sumati Bhatia
Full text not available from this repository: check for access using links below.
DOI (Published version): 10.1021/acs.jmedchem.1c00794
Abstract
The development of multivalent sialic acid-based inhibitors active against a variety of influenza A virus (IAV) strains has been hampered by high genetic and structural variability of the targeted viral hemagglutinin (HA). Here, we addressed this challenge by employing sialylated polyglycerols (PGs)...
| Published in: | Journal of Medicinal Chemistry |
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| ISSN: | 0022-2623 1520-4804 |
| Published: |
American Chemical Society (ACS)
2021
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| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa64860 |
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| Abstract: |
The development of multivalent sialic acid-based inhibitors active against a variety of influenza A virus (IAV) strains has been hampered by high genetic and structural variability of the targeted viral hemagglutinin (HA). Here, we addressed this challenge by employing sialylated polyglycerols (PGs). Efficacy of prototypic PGs was restricted to a narrow spectrum of IAV strains. To understand this restriction, we selected IAV mutants resistant to a prototypic multivalent sialylated PG by serial passaging. Resistance mutations mapped to the receptor binding site of HA, which was accompanied by altered receptor binding profiles of mutant viruses as detected by glycan array analysis. Specifying the inhibitor functionalization to 2,6-α-sialyllactose (SL) and adjusting the linker yielded a rationally designed inhibitor covering an extended spectrum of inhibited IAV strains. These results highlight the importance of integrating virological data with chemical synthesis and structural data for the development of sialylated PGs toward broad anti-influenza compounds. |
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| Keywords: |
Carbohydrates, Chemical biology, Genetics, Receptors, Viruses |
| College: |
Faculty of Science and Engineering |
| Issue: |
17 |
| Start Page: |
12774 |
| End Page: |
12789 |