Antiviral properties of trans-δ-viniferin derivatives against enveloped viruses

Zwygart, Arnaud Charles-Antoine; Medaglia, Chiara; Huber, Robin; Poli, Romain; Marcourt, Laurence; Schnée, Sylvain; Michellod, Emilie; Mazel-Sanchez, Béryl; Constant, Samuel; Huang, Song; Bekliz, Meriem; Clément, Sophie; Gindro, Katia; Queiroz, Emerson Ferreira; Tapparel, Caroline

doi:10.1016/j.biopha.2023.114825

Cited by 7 publications

(2 citation statements)

References 29 publications

(52 reference statements)

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“…Cell viability was assessed by MTT assay as described in [16] while viability in ex vivo tissues was assessed by Resazurin treatment as described in [17].…”

Section: Cell Viability Assaymentioning

confidence: 99%

Development of Broad-spectrum β-cyclodextrins-Based Nanomaterials Against Influenza Viruses

Zwygart,

Medaglia,

Zhu

et al. 2024

Preprint

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In recent decades, epidemics and pandemics have multiplied throughout the world, with viruses generally being the primary agents responsible. Among these, influenza viruses play a key role, as they cause severe respiratory distress, representing a major threat to public health. To enhance the response to viral disease outbreaks, there is a need for ready-to-use broad-spectrum antivirals. We have engineered macromolecules (named CD-SA) consisting of a β-cyclodextrin (CD) scaffold modified with hydrophobic linkers in the primary face, onto which unitary sialic acid (SA) epitopes are covalently grafted, this to mimic influenza virus host receptors. In this study, we demonstrated that CD-SA, with a unitary SA, without extensive polysaccharides or specific connectivity, acts as a potent virucidal antiviral against several variants of human influenza type A and type B viruses. We also assessed the genetic barrier to resistance of CD-SA in vitro and successfully delayed emergence of resistance by combining CD-SA with interferon-λ1 (IFN λ1). Finally, we completed the characterization of the antiviral activity by conducting both ex vivo and in vivo studies, demonstrating a potent antiviral effect in human airway epithelia and in a mouse model of infection, higher than that of Oseltamivir, a currently approved anti-influenza antiviral.

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“…Cell viability was assessed by MTT assay as described in [16] while viability in ex vivo tissues was assessed by Resazurin treatment as described in [17].…”

Section: Cell Viability Assaymentioning

confidence: 99%

Development of Broad-spectrum β-cyclodextrins-Based Nanomaterials Against Influenza Viruses

Zwygart,

Medaglia,

Zhu

et al. 2024

Preprint

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“…Based on this knowledge, we have recently used a mixture of secreted enzymes, the “secretome”, containing these laccases obtained from the culture of B. cinerea (K16 strain, see the experimental section for more details) as a tool to produce natural product derivatives for drug discovery applications. Using this approach, a series of dimeric stilbene derivatives have been obtained, some of which exhibit potent antifungal, antiviral, and antibacterial properties ( Gindro et al, 2017 ; Righi et al, 2020 ; Huber et al, 2022a ; Huber et al, 2023 ; Zwygart et al, 2023 ). Although trimers and tetramers of stilbenes have been isolated and characterized in many plants ( Shen et al, 2017 ), it has not been possible to generate them using this chemo-enzymatic approach starting from stilbene monomers.…”

Section: Introductionmentioning

confidence: 99%

Study of phenoxy radical couplings using the enzymatic secretome of Botrytis cinerea

Huber,

Marcourt,

Félix

et al. 2024

Front. Chem.

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Phenoxy radical coupling reactions are widely used in nature for the synthesis of complex molecules such as lignin. Their use in the laboratory has great potential for the production of high value compounds from the polyphenol family. While the enzymes responsible for the generation of the radicals are well known, the behavior of the latter is still enigmatic and difficult to control in a reaction flask. Previous work in our laboratory using the enzymatic secretome of B. cinerea containing laccases has shown that incubation of stilbenes leads to dimers, while incubation of phenylpropanoids leads to dimers as well as larger coupling products. Building on these previous studies, this paper investigates the role of different structural features in phenoxy radical couplings. We first demonstrate that the presence of an exocyclic conjugated double bond plays a role in the generation of efficient reactions. In addition, we show that the formation of phenylpropanoid trimers and tetramers can proceed via a decarboxylation reaction that regenerates this reactive moiety. Lastly, this study investigates the reactivity of other phenolic compounds: stilbene dimers, a dihydro-stilbene, a 4-O-methyl-stilbene and a simple phenol with the enzymatic secretome of B. cinerea. The observed efficient dimerization reactions consistently correlate with the presence of a para-phenol conjugated to an exocyclic double bond. The absence of this structural feature leads to variable results, with some compounds showing low conversion or no reaction at all. This research has allowed the development of a controlled method for the synthesis of specific dimers and tetramers of phenylpropanoid derivatives and novel stilbene derivatives, as well as an understanding of features that can promote efficient radical coupling reactions.

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Development of Broad‐Spectrum β‐Cyclodextrins‐Based Nanomaterials Against Influenza Viruses

Zwygart,

Medaglia,

Zhu

et al. 2024

Journal of Medical Virology

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In recent decades, epidemics and pandemics have multiplied throughout the world, with viruses generally being the primary responsible agents. Among these, influenza viruses play a key role, as they potentially cause severe respiratory distress, representing a major threat to public health. Our study aims to develop new broad‐spectrum antivirals against influenza to improve the response to viral disease outbreaks. We engineered macromolecules (named CD‐SA) consisting of a β‐cyclodextrin scaffold modified with hydrophobic linkers in the primary face, onto which unitary sialic acid epitopes are covalently grafted to mimic influenza virus−host receptors. We assessed the antiviral efficacy, mechanism of action, and the genetic barrier to resistance of this compound against influenza in vitro, ex vivo, and in vivo. We demonstrated that CD‐SA, with a unitary SA, without extensive polysaccharides or specific connectivity, acts as a potent virucidal antiviral against several human influenza A and B viruses. Additionally, CD‐SA displayed antiviral activity against SARS‐CoV‐2, a virus that also relies on sialic acid for attachment. We then assessed the genetic barrier to resistance for CD‐SA. While resistance emerged after six passages with CD‐SA alone, the virus remained sensitive through eight passages when co‐treated with interferon‐λ1 (IFN λ1). Finally, we completed the characterization of the antiviral activity by conducting both ex vivo and in vivo studies, demonstrating a potent antiviral effect in human airway epithelia and in a mouse model of infection, higher than that of Oseltamivir, a currently approved anti‐influenza antiviral. The findings presented in this study support the potential therapeutic utility of a novel β‐cyclodextrin‐based nanomaterial for the treatment of influenza infections and potentially other sialic acid‐dependent viruses.

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Antiviral properties of trans-δ-viniferin derivatives against enveloped viruses

Cited by 7 publications

References 29 publications

Development of Broad-spectrum β-cyclodextrins-Based Nanomaterials Against Influenza Viruses

Development of Broad-spectrum β-cyclodextrins-Based Nanomaterials Against Influenza Viruses

Study of phenoxy radical couplings using the enzymatic secretome of Botrytis cinerea

Development of Broad‐Spectrum β‐Cyclodextrins‐Based Nanomaterials Against Influenza Viruses

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