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  3. Identification of antiviral compounds against equid herpesvirus-1 using real-time cell assay screening: Efficacy of decitabine and valganciclovir alone or in combination

Identification of antiviral compounds against equid herpesvirus-1 using real-time cell assay screening: Efficacy of decitabine and valganciclovir alone or in combination

  • Antiviral Res. 2020 Nov;183:104931. doi: 10.1016/j.antiviral.2020.104931.
Côme Thieulent 1,  Erika S Hue 2,  Gabrielle Sutton 1,  Christine Fortier 2,  Patrick Dallemagne 3,  Stephan Zientara 4,  Hélène Munier-Lehmann 5,  Aymeric Hans 6,  Romain Paillot 1,  Pierre-Olivier Vidalain 7,  Stéphane Pronost 8
Affiliations

Affiliations

  • 1 LABÉO Frank Duncombe, 14280, Saint-Contest, France; Normandie Univ, Unicaen, BIOTARGEN EA7450, 14280, Saint-Contest, France.
  • 2 LABÉO Frank Duncombe, 14280, Saint-Contest, France; Normandie Univ, Unicaen, BIOTARGEN EA7450, 14280, Saint-Contest, France; Normandie Univ, UNICAEN, ImpedanCELL, 14280, Saint-Contest, France.
  • 3 Normandie Univ, UNICAEN, CERMN, 14000, Caen, France.
  • 4 Université Paris-Est, Laboratoire de Santé Animale, ANSES, INRAE, ENVA, UMR 1161 Virologie, 94700, Maisons-Alfort, France.
  • 5 Institut Pasteur, Unité de Chimie et Biocatalyse, CNRS UMR 3523, 75015, Paris, France.
  • 6 ANSES, Laboratoire de Santé Animale, Site de Normandie, PhEED Unit, 14430, Goustranville, France.
  • 7 CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France; Equipe Chimie et Biologie, Modélisation et Immunologie pour La Thérapie (CBMIT), Université Paris Descartes, CNRS UMR 8601, 75006, Paris, France.
  • 8 LABÉO Frank Duncombe, 14280, Saint-Contest, France; Normandie Univ, Unicaen, BIOTARGEN EA7450, 14280, Saint-Contest, France; Normandie Univ, UNICAEN, ImpedanCELL, 14280, Saint-Contest, France. Electronic address: stephane.pronost@laboratoire-labeo.fr.
PMID: 32926887 DOI: 10.1016/j.antiviral.2020.104931
Abstract

Equid herpesvirus-1 infections cause respiratory, neurological and reproductive syndromes. Despite preventive treatments with vaccines, resurgence of EHV-1 Infection still constitutes a major threat to equine industry. However, no Antiviral compound is available to treat infected horses. In this study, 2891 compounds were screened against EHV-1 using impedance measurement. 22 compounds have been found to be effective in vitro against EHV-1. Valganciclovir, ganciclovir, decitabine, aphidicolin, idoxuridine and pritelivir (BAY 57-1293) are the most effective compounds identified, and their Antiviral potency was further assessed on E. Derm, RK13 and EEK cells and against 3 different field strains of EHV-1 (ORF30 2254 A/G/C). We also provide evidences of synergistic interactions between valganciclovir and decitabine in our in vitro Antiviral assay as determined by MacSynergy II, isobologramm and Chou-Talalay methods. Finally, we showed that deoxycytidine reverts the Antiviral effect of decitabine, thus supporting some competition at the level of nucleoside phosphorylation by deoxycytidine kinase and/or DNA synthesis. Deoxycitidine analogues, like decitabine, is a family of compounds identified for the first time with promising Antiviral efficacy against herpesviruses.

Keywords

Antiviral; Chemical library screening; Decitabine; Equid herpesvirus-1; Ganciclovir; Real-time cell assay; Synergism.

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