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

The research explores potential antiviral treatments for equid herpesvirus-1 (EHV-1), a virus that negatively impacts the equine industry by causing respiratory, neurological, and reproductive syndromes in horses. The researchers identified promising antiviral compounds, including the novel finding of the effectiveness of decitabine, a deoxycytidine analogue, and found synergistic interactions between valganciclovir and decitabine.

Overview of the Study

• The study aims to identify potential antiviral compounds to treat equid herpesvirus-1 (EHV-1), a significant viral threat to horses.
• The researchers tested 2891 compounds against EHV-1 using impedance measurement, a method that allows for real-time monitoring of cell behavior without the use of labeling.
• Out of the compounds tested, 22 showed effectiveness against the virus in vitro, indicating potential for developing antiviral therapeutics.

Noteworthy Findings

• Valganciclovir, ganciclovir, decitabine, aphidicolin, idoxuridine, and pritelivir (BAY 57-1293) were identified as the most effective compounds against EHV-1.
• Their antiviral potency was further confirmed through tests on E. Derm, RK13, and EEK cells, and against three different field strains of EHV-1.
• Significantly, decitabine, a deoxycytidine analogue, was identified for the first time to have promising antiviral efficacy against herpesviruses.

Synergism between Antiviral Compounds

• The study also found evidence of synergistic interactions between valganciclovir and decitabine in their in vitro antiviral assay, as determined through the use of MacSynergy II, isobologram, and Chou-Talalay methods.
• This implies that the combination of these two drugs may have greater antiviral effects, offering a new avenue for treating EHV-1 infections in horses.

Role of Deoxycytidine

• The study demonstrated that deoxycytidine, a molecule similar to decitabine, can reverse the antiviral effect of decitabine. This suggests some level of competition at the level of nucleoside phosphorylation by deoxycytidine kinase and/or DNA synthesis.
• Understanding this reversible influence of deoxycytidine on decitabine’s antiviral efficacy contributes to our knowledge of how these compounds work, which will be vital for further drug development.