tetano
Editor, Senior Moderator
J Med Chem
. 2022 May 12.
doi: 10.1021/acs.jmedchem.2c00319. Online ahead of print.
Preventing Influenza A Virus Infection by Mixed Inhibition of Neuraminidase and Hemagglutinin by Divalent Inhibitors
Xuan Wei[SUP] 1 [/SUP], Wenjuan Du[SUP] 2 [/SUP], Margherita Duca[SUP] 1 [/SUP], Guangyun Yu[SUP] 1 [/SUP], Erik de Vries[SUP] 2 [/SUP], Cornelis A M de Haan[SUP] 2 [/SUP], Roland J Pieters[SUP] 1 [/SUP]
Affiliations
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[SUP]4[/SUP]-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.
. 2022 May 12.
doi: 10.1021/acs.jmedchem.2c00319. Online ahead of print.
Preventing Influenza A Virus Infection by Mixed Inhibition of Neuraminidase and Hemagglutinin by Divalent Inhibitors
Xuan Wei[SUP] 1 [/SUP], Wenjuan Du[SUP] 2 [/SUP], Margherita Duca[SUP] 1 [/SUP], Guangyun Yu[SUP] 1 [/SUP], Erik de Vries[SUP] 2 [/SUP], Cornelis A M de Haan[SUP] 2 [/SUP], Roland J Pieters[SUP] 1 [/SUP]
Affiliations
- PMID: 35549211
- DOI: 10.1021/acs.jmedchem.2c00319
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[SUP]4[/SUP]-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.