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

2023; Elsevier BV; Volume: 163; Linguagem: Inglês

10.1016/j.biopha.2023.114825

1950-6007

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

Phytochemistry and Biological Activities

Over the last century, the number of epidemics caused by RNA viruses has increased and the current SARS-CoV-2 pandemic has taught us about the compelling need for ready-to-use broad-spectrum antivirals. In this scenario, natural products stand out as a major historical source of drugs. We analyzed the antiviral effect of 4 stilbene dimers [1 (trans-δ-viniferin); 2 (11',13'-di-O-methyl-trans-δ-viniferin), 3 (11,13-di-O-methyl-trans-δ-viniferin); and 4 (11,13,11',13'-tetra-O-methyl-trans-δ-viniferin)] obtained from plant substrates using chemoenzymatic synthesis against a panel of enveloped viruses. We report that compounds 2 and 3 display a broad-spectrum antiviral activity, being able to effectively inhibit several strains of Influenza Viruses (IV), SARS-CoV-2 Delta and, to some extent, Herpes Simplex Virus 2 (HSV-2). Interestingly, the mechanism of action differs for each virus. We observed both a direct virucidal and a cell-mediated effect against IV, with a high barrier to antiviral resistance; a restricted cell-mediated mechanism of action against SARS-CoV-2 Delta and a direct virustatic activity against HSV-2. Of note, while the effect was lost against IV in tissue culture models of human airway epithelia, the antiviral activity was confirmed in this relevant model for SARS-CoV-2 Delta. Our results suggest that stilbene dimer derivatives are good candidate models for the treatment of enveloped virus infections.