The acyclic nucleoside analogue penciclovir is a potent inhibitor of equine herpesvirus type 1 (EHV-1) in tissue culture and in a murine model.
Equine herpesvirus type 1 (EHV-1) was sensitive to the nucleoside analogue penciclovir (PCV) when tested in tissue culture; the ED50 was 1.6 micrograms/ml. Drug-resistant mutants were selected which were found to be TK-defective and approx. 45-fold less sensitive to PCV compared with the parental strain. PCV was compared with the phosphonyl derivative, HPMPA in mice infected with EHV-1. Both drugs were shown to be effective in vivo, limiting wild-type virus replication in respiratory tissues, and reducing viraemia. The treated mice also showed less clinical signs and reduced histopathology compared with placebo-treated controls. The establishment of latent EHV-1 in the mice, however, was not prevented. The results obtained with mice suggest that antiviral chemotherapy may be practical in the horse and that this possibility is worthy of further investigation in the natural host.
de la Fuente
R
R
Department of Clinical Veterinary Medicine, University of Cambridge, UK.
Awan
A R
AR
Field
H J
HJ
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D004352:Drug Resistance, Microbial; D005260:Female; D006147:Guanine; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000473:pathology; D004861:Herpesvirus 1, Equid / Q000187:drug effects* / Q000235:genetics; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D013937:Thymidine Kinase / Q000378:metabolism
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C053539:penciclovir; D006147:Guanine; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D013937:Thymidine Kinase; D000225:Adenine; D000212:Acyclovir