Preventing Influenza A Virus Infection by Mixed Inhibition of Neuraminidase and Hemagglutinin by Divalent Inhibitors

Xuan Wei; Wenjuan Du; Margherita Duca; Guangyun Yu; Erik de Vries; Cornelis A M de Haan; Roland J Pieters

doi:10.1021/acs.jmedchem.2c00319

Preventing Influenza A Virus Infection by Mixed Inhibition of Neuraminidase and Hemagglutinin by Divalent Inhibitors

Xuan Wei, Wenjuan Du, Margherita Duca, Guangyun Yu, Erik de Vries, Cornelis A M de Haan, Roland J Pieters

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Divalent inhibitors of the neuraminidase enzyme (NA) of the Influenza A virus were synthesized with vastly different spacers. The spacers varied from 14 to 56 atoms and were relatively rigid by way of the building blocks and their connection by CuAAC. As the ligand for these constructs, a Δ 4-β-d-glucoronide was used, which can be prepared form N-acetyl glucosamine. This ligand showed good NA inhibitory potency but with room for improvement by multivalency enhancement. The synthesized compounds showed modest potency enhancement in NA activity assays but a sizeable potency increase in a 4-day cytopathic effect assay. The demonstration that the compounds can also inhibit hemagglutinin in addition to NA may be the cause of the enhancement.

Original language	English
Pages (from-to)	7312-7323
Number of pages	12
Journal	Journal of Medicinal Chemistry
Volume	65
Issue number	10
Early online date	12 May 2022
DOIs	https://doi.org/10.1021/acs.jmedchem.2c00319
Publication status	Published - 26 May 2022

Bibliographical note

Funding Information:
X.W. and W.D. gratefully acknowledge financial support by a scholarship from the China Scholarship Council CSC (http://www.csc.edu.cn/), files nos. 201606230221 and 201603250057, respectively. The academic license for OpenEye software was kindly provided by OpenEye Scientific Software Inc. to the laboratory of Roland Pieters.

Funding Information:
X.W. and W.D. gratefully acknowledge financial support by a scholarship from the China Scholarship Council CSC ( http://www.csc.edu.cn/ ), files nos. 201606230221 and 201603250057, respectively. The academic license for OpenEye software was kindly provided by OpenEye Scientific Software Inc. to the laboratory of Roland Pieters.

Publisher Copyright:
© 2022 American Chemical Society.

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acs.jmedchem.2c00319Final published version, 2.17 MBLicence: CC BY

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title = "Preventing Influenza A Virus Infection by Mixed Inhibition of Neuraminidase and Hemagglutinin by Divalent Inhibitors",

abstract = "Divalent inhibitors of the neuraminidase enzyme (NA) of the Influenza A virus were synthesized with vastly different spacers. The spacers varied from 14 to 56 atoms and were relatively rigid by way of the building blocks and their connection by CuAAC. As the ligand for these constructs, a Δ 4-β-d-glucoronide was used, which can be prepared form N-acetyl glucosamine. This ligand showed good NA inhibitory potency but with room for improvement by multivalency enhancement. The synthesized compounds showed modest potency enhancement in NA activity assays but a sizeable potency increase in a 4-day cytopathic effect assay. The demonstration that the compounds can also inhibit hemagglutinin in addition to NA may be the cause of the enhancement. ",

author = "Xuan Wei and Wenjuan Du and Margherita Duca and Guangyun Yu and \{de Vries\}, Erik and \{de Haan\}, \{Cornelis A M\} and Pieters, \{Roland J\}",

note = "Funding Information: X.W. and W.D. gratefully acknowledge financial support by a scholarship from the China Scholarship Council CSC (http://www.csc.edu.cn/), files nos. 201606230221 and 201603250057, respectively. The academic license for OpenEye software was kindly provided by OpenEye Scientific Software Inc. to the laboratory of Roland Pieters. Funding Information: X.W. and W.D. gratefully acknowledge financial support by a scholarship from the China Scholarship Council CSC ( http://www.csc.edu.cn/ ), files nos. 201606230221 and 201603250057, respectively. The academic license for OpenEye software was kindly provided by OpenEye Scientific Software Inc. to the laboratory of Roland Pieters. Publisher Copyright: {\textcopyright} 2022 American Chemical Society.",

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AU - de Vries, Erik

AU - de Haan, Cornelis A M

AU - Pieters, Roland J

N1 - Funding Information: X.W. and W.D. gratefully acknowledge financial support by a scholarship from the China Scholarship Council CSC (http://www.csc.edu.cn/), files nos. 201606230221 and 201603250057, respectively. The academic license for OpenEye software was kindly provided by OpenEye Scientific Software Inc. to the laboratory of Roland Pieters. Funding Information: X.W. and W.D. gratefully acknowledge financial support by a scholarship from the China Scholarship Council CSC ( http://www.csc.edu.cn/ ), files nos. 201606230221 and 201603250057, respectively. The academic license for OpenEye software was kindly provided by OpenEye Scientific Software Inc. to the laboratory of Roland Pieters. Publisher Copyright: © 2022 American Chemical Society.

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Preventing Influenza A Virus Infection by Mixed Inhibition of Neuraminidase and Hemagglutinin by Divalent Inhibitors

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