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

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Normand, Camille | Fortier, Christine | Sutton, Gabrielle | Thieulent, Côme | Marcillaud Pitel, Christel | Legrand, Loïc | Pronost, Stéphane | Hue, Erika

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International audience. 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.

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