Antiviral activity of Α-hydroxytropolones on caprine alphaherpesvirus 1 in vitro

Abstract

The emergence of human alphaherpesvirus strains (i.e. HHV-1 and -2) resistant to commonly used antiviral drugs has prompted the research for alternative, biologically active anti-herpetic agents. Natural-product and synthetic α-hydroxytropolones (αHTs) have been identified as lead therapeutic agents for a number of infections, including HHV-1 and -2, and several veterinary herpesviruses, i.e. bovine alphaherpesvirus 1 (BoHV-1), equine alphaherpesvirus 1 (EHV-1) and feline alphaherpesvirus 1 (FHV-1). In the present study we evaluated the activity in vitro of two natural and two synthetic α-hydroxytropolones (αHTs) against Caprine alphaherpesvirus 1 (CpHV-1) which is regarded as a useful homologous animal model for the study of HSV-2 infection, chiefly for the assessment of antiviral drugs in in vivo studies. AlphaHTs were able to decrease significantly CpHV-1 viral titres up to 4.25 log10 TCID50/50 μl and suppressed extensively CpHV-1 nucleic acids up to 8.71 log10 viral DNA copy number/10 μl. This study demonstrated the efficacy of αHTs against CpHV-1 in vitro, adding to their activity observed against the human and animal alphaherpesviruses in vitro. The activity of αHTs against CpHV-1 appeared similar but not identical to the patterns of activity observed against other alphaherpesviruses, suggesting virus-related variability in terms of response to specific αHT molecules. These findings open several perspectives in terms of future studies using the CpHV-1 homologous animal model, for the development of therapeutic tools against herpesviruses.