Anti-HSV activity and mode of action study of α-pyrone carboxamides

Abstract

The clinical management of herpes virus diseases is limited due to ineffective clearance of virus particles and frequent emergence of drug-resistant viruses, particularly in immunocompromised patients, pregnant women and neonates. In our continued quest for new antiviral leads, α-pyrone carboxamide propanol derivatives were synthesized and evaluated in HSV infected Vero cells. Compound 3d showed potent antiviral activity against HSV-IF (EC₅₀ = 9.8 μg ml⁻¹ and EC₉₉ = 18.0 μg ml⁻¹) and HSV-2G (EC₅₀ = 12.4 μg ml⁻¹ and EC₉₉ = 24.0 μg ml⁻¹) at 4–6 h post-infection. The mode of action studies demonstrated that 3d did not interfere in viral attachment or penetration, however, it reduced the expression of ICP4 and ICP27 (immediate-early gene products) as well as the HSV DNA polymerase.