Antiviral activity of PHA767491 on Caprine alphaherpesvirus 1 in vitro. (October 2019)

• Record Type: Journal Article
• Authors: Lanave, Gianvito; Lucente, Maria S.; Siciliano, Pietro; Zizzadoro, Claudia; Trerotoli, Paolo; Martella, Vito; Buonavoglia, Canio; Tempesta, Maria; Camero, Michele
• Is Part Of: Research in veterinary science. Volume 126(2019)
• Page Start: 113
• Page End: 117
• Publication Date: 2019-10
• Subjects: PHA767491 -- Caprine alphaherpesvirus 1 -- Antiviral -- Cells; Veterinary medicine -- Periodicals; Veterinary Medicine -- Periodicals; Médecine vétérinaire -- Périodiques; Médecine vétérinaire -- Recherche -- Périodiques; Diergeneeskunde; 636.089
• DOI: 10.1016/j.rvsc.2019.08.019
• Languages: English
• ISSNs: 0034-5288

Abstract

Abstract: Caprine alphaherpesvirus 1 (CpHV-1) induces genital lesions in its natural host similar to those caused by Human alphaherpesvirus 2 (HHV-2), commonly named herpes simplex virus 2 (HSV-2) in human patients. CpHV-1 infection in goats could represent a useful homologous animal model for the study of HSV-2 infection, chiefly for the assessment of antiviral drugs in in vivo studies. PHA767491 is a potent inhibitor of HSV-1 and HSV-2, being able to limit replication of HHVs both in vitro and in the mouse model. In the present study the antiviral efficacy of PHA767491 against CpHV-1 was evaluated in vitro in MDBK cells. PHA767491 inhibited significantly CpHV-1 replication in a dose-dependent fashion by up to 2.50 log10 TCID50 /50 μl and was able to decrease viral DNA by nearly 8 log10. These findings confirm that PHA767491 is highly effective not only against simplexviruses (HSV-1 and HSV-2), but also against the varicellovirus CpHV-1. Experiments will be necessary to assess whether PHA767491 is suitable for treatment of vaginal lesions in CpHV-1-goat model. This could provide hints for the therapy of genital alphaherpesvirus infections in humans. Highlights: PHA767491 is a dual CDC7/CDK9 inhibitor with anti-cancer effects. PHA767491 recently proved to have potent activity against human simplexviruses. Inhibitory activity of PHA767491 against CpHV-1 was evaluated in vitro . PHA767491 decreased CpHV-1 replication and DNA copies. In vivo experiments will be useful to assess efficacy of PHA767491 against CpHV-1.