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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 Δ⁴-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.

SUBMITTER: Wei X

PROVIDER: S-EPMC9150099 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Wei Xuan X Du Wenjuan W Duca Margherita M Yu Guangyun G de Vries Erik E de Haan Cornelis A M CAM Pieters Roland J RJ

Journal of medicinal chemistry 20220512 10

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 <i>N</i>-acetyl glucosamine. This ligand showed good NA inhibitory potency but with room for improvement by multivalency enhancement. The synth ...[more]

PMID: 35549211

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