Evaluation of the antiviral activity of (1′S,2′R)-9-[[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl]guanine (A-5021) against equine herpesvirus type 1 in cell monolayers and equine nasal mucosal explants

Equine herpesvirus 1 (EHV1) is a ubiquitous equine alphaherpesvirus that causes respiratory disease, neurological symptoms and abortions. Current vaccines are not fully protective and effective therapeutics are lacking. A-5021 [(1′S,2′R)-9-[[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl]guanine], previously shown to possess potent anti-herpetic activity against most human herpesviruses, was evaluated for its potential to inhibit EHV1 replication. In equine embryonic lung (EEL) cells, infected with either a non-neurovirulent (97P70) or a neurovirulent (03P37) EHV1 isolate, A-5021 proved to be about 15-fold more potent than acyclovir in inhibiting viral replication. Moreover, in equine nasal mucosal explants, A-5021 (at 8 and 32 μM) was able to completely inhibit viral plaque formation whereas acyclovir did not exert an antiviral effect at these concentrations. Our data demonstrate that A-5021 is a potent inhibitor of EHV1 replication and may have potential for the treatment and/or prophylaxis of infections with this virus.

► Anti-EHV1 activity of A-5021 was tested in EEL cells and equine nasal explants. ► A-5021 proves about 15-fold more potent than acyclovir in EEL cells. ► Contrary to acyclovir, A-5021 completely inhibits EHV1 plaque formation in explants. ► A-5021 is a potent inhibitor of EHV1 replication.