Antiviral activity of amenamevir alone and in combination with ganciclovir against equine herpesvirus 1.

Equine herpesvirus 1 (EHV-1) causes respiratory disease, abortion, and equine herpesvirus myeloencephalopathy (EHM), a neurological disorder characterized by ataxia and hindlimb paralysis. Although EHM remains a major concern in the equine industry, effective antiviral treatment options are limited. This study evaluated the antiviral activity of amenamevir, a helicase-primase complex inhibitor, against multiple EHV-1 strains using real-time cell analysis (RTCA) and quantitative PCR (qPCR), and compared its potency with those of ganciclovir, acyclovir, and penciclovir. Eight EHV-1 strains associated with different clinical manifestations and characterized by A, G, or C at position 2254 of open reading frame 30, which encodes the viral DNA polymerase, were examined. RTCA-based half-maximal inhibitory concentration (IC50) values were calculated from inhibition rates based on the area under the normalized cell index curve. Across the eight strains, IC50 values were 0.45-2.31 μg/mL for amenamevir, 0.45-3.95 μg/mL for ganciclovir, 17.93-50.15 μg/mL for acyclovir, and 8.38-24.52 μg/mL for penciclovir. qPCR analysis, based on concentrations required to achieve a 1-log10 reduction in viral genome copy number, showed a similar overall trend. Amenamevir exhibited in vitro antiviral activity against EHV-1, with potency comparable to that of ganciclovir and greater than those of acyclovir and penciclovir. SynergyFinder analysis showed synergistic interactions between amenamevir and ganciclovir within selected concentration ranges against EHV-1 strains in both the Bliss independence and ZIP models. These findings support further investigation of amenamevir, alone and in combination with ganciclovir, as a candidate antiviral compound for the treatment of EHV-1 infection.