In vitro evaluation of nine antiviral compounds for their potential effect against equid alphaherpesviruses EHV-4 and EHV-3.

Camille Normand (1, 2) , Christine Fortier (1, 3, 2) , Gabrielle Sutton (1, 2) , Côme Thieulent (1, 2) , Christel Marcillaud Pitel (4) , Loïc Legrand (1, 2) , Stéphane Pronost (1, 2, 3) , Erika Hue (1, 3, 2)

1 LABÉO - LABÉO, Pôle d’analyses et de recherche de Normandie
2 BIOTARGEN - Biologie, génétique et thérapies ostéoarticulaires et respiratoires
3 ImpedanCELL
4 RESPE - Réseau d'Epidémio-Surveillance en Pathologie Équine

Introduction: Equine herpesvirus 4 (EHV-4) is a common respiratory pathogen of the horse, sporadically causing abortions or neonatal deaths. Despite preventive measures such as vaccination, the resurgence of EHV-4 infection remains a significant threat to the equine industry. Equine coital exanthema is an acute viral infection of the horse caused by EHV-3. Despite the limitations or absence of vaccines, very few studies have been conducted on the search for antiviral molecules against these viruses. Objectives: to evaluate the efficacy of nine antiviral compounds previously described with antiviral properties against EHV-1 against EHV-4 and EHV-3. Study design: Determination of the effect of 8 concentrations of nine selected compounds (previously identified for their effect on EHV-1) by Real-Time Cell Analysis (RTCA) on 2 in vitro models : CCL26 infected with EHV-4 and E.derm cells with EHV-3. Cytopathic effects were monitored by RTCA (xCELLigence® and Incucyte®) and the viral load (EHV-4 and EHV-3) was quantified by qPCR. EC50 values for both xCELLigence® and qPCR methods were determined. Results: The EC50 values show that seven molecules have antiviral potential to prevent EHV-4 infection of CCL26 in vitro. The nucleoside analogues aciclovir and vidarabine are not effective in preventing EHV-4 infection of CCL26. Aphidicolin is the most effective compound with an EC50 value of 1.63±0.76 µM determined by xCELLigence and 0.25±0.12 µM when determined by qPCR. All 9 compounds are effective against EHV-3. Pritelivir and cidofovir are the least effective molecules against EHV-3 (EC50 >50 µM). Aphidicolin is also the most effective compound against EHV-3 with an EC50 value of 2.43±0.02 µM (xCELLigence) and 1.63±0.48 µM (qPCR). Conclusions: Seven antiviral compounds (ganciclovir, valganciclovir, decitabine, idoxuridine, pritelivir, cidofovir and aphidicolin) prevent the cytopathic effect of EHV-4 on CCL26 cells in vitro. Aciclovir, the most widely used antiviral against alpha-herpesviruses in vivo, does not appear to be effective against EHV-4 in vitro. The 9 compounds are effective against EHV-3. Aphidicolin is also the most effective compound against EHV-4 and EHV-3. Declarations: The authors declare no conflicts of interest.

Mots clés: antiviral; EHV-4; EHV-3; equid herpesvirus; horse

Domaines: Médecine vétérinaire et santé animale

Camille Normand, Christine Fortier, Gabrielle Sutton, Côme Thieulent, Christel Marcillaud Pitel, et al.. In vitro evaluation of nine antiviral compounds for their potential effect against equid alphaherpesviruses EHV-4 and EHV-3.. 12th International congress for veterinary virology, Sep 2022, Ghent, Belgium. ⟨hal-03808041⟩