title: 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.
abstract: 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 32μM) 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.
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium. Electronic address: Sarah.Glorieux@UGent.be.
authors.forename: Sarah
authors.initials: S
authors.lastname: Glorieux
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium. Electronic address: Annelies.Vandekerckhove@UGent.be.
authors.forename: Annelies P
authors.initials: AP
authors.lastname: Vandekerckhove
authors.affiliation: Okapi Sciences NV, Ambachtenlaan 1, 3001 Heverlee, Belgium. Electronic address: nesya.goris@okapi-sciences.com.
authors.forename: Nesya
authors.initials: N
authors.lastname: Goris
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium. Electronic address: Xiaoyun.Yang@UGent.be.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium. Electronic address: Lennert.Steukers@UGent.be.
authors.forename: Lennert
authors.initials: L
authors.lastname: Steukers
authors.affiliation: Department of Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium. Electronic address: Gerlinde.VandeWalle@UGent.be.
authors.forename: Gerlinde R
authors.initials: GR
authors.lastname: Van de Walle
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium. Electronic address: Siska.Croubels@UGent.be.
authors.forename: Siska
authors.initials: S
authors.lastname: Croubels
authors.affiliation: Rega Institute for Medical Research, Department of Microbiology and Immunology, Katholieke Universiteit Leuven, Minderbroederstraat 10, 3000 Leuven, Belgium. Electronic address: johan.neyts@rega.kuleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium. Electronic address: Hans.Nauwynck@UGent.be.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nauwynck
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000662:veterinary* / Q000821:virology; D004861:Herpesvirus 1, Equid / Q000187:drug effects* / Q000502:physiology; D006734:Horse Diseases / Q000188:drug therapy* / Q000821:virology; D006736:Horses; D066298:In Vitro Techniques; D009297:Nasal Mucosa / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: C111645:9-((cis-1,2-bis(hydroxymethyl)cycloprop-1-yl)methyl)guanine; D000998:Antiviral Agents; D006147:Guanine