Efficacy of a helicase-primase inhibitor in animal models of ocular herpes simplex virus type 1 infection.
OBJECTIVE
The aim of this study was to evaluate the effect of BAY 57-1293, a helicase-primase inhibitor, on herpes simplex virus type 1 (HSV-1) reactivation in mice and its efficacy on established disease in rabbits.


METHODS
BALB/c mice latent for McKrae-strain HSV-1 were reactivated via heat stress, treated with BAY 57-1293, and their corneas were swabbed for virus or the trigeminal ganglia (TG) obtained for quantification of viral DNA. New Zealand white rabbits were infected and treated topically or orally in comparison with trifluridine or valacyclovir.


RESULTS
Oral BAY 57-1293 suppressed reactivation in HSV-1-infected mice and reduced the viral load in TG up to four orders of magnitude. In the rabbits, the therapeutic efficacies of topical BAY 57-1293 and trifluridine were similar. Once-daily oral BAY 57-1293 was significantly more effective than valacyclovir and as effective as twice a day topical trifluridine.


CONCLUSIONS
BAY 57-1293 may be more effective than valacyclovir, without the cytotoxicity or potential healing retardation seen with trifluridine. Oral BAY 57-1293 may be a substitute for eye drops as an effective treatment for herpetic keratitis and might be useful in treating stromal keratitis and iritis, as well as preventing recurrences of ocular herpes.
Kaufman
Herbert E
HE
Department of Ophthalmology, LSU Eye Center, Louisiana State University Health Sciences Center in New Orleans, New Orleans, LA, USA. hkaufm@lsuhsc.edu
Varnell
Emily D
ED
Gebhardt
Bryan M
BM
Thompson
Hilary W
HW
Atwal
Ephraim
E
Rübsamen-Waigmann
Helga
H
Kleymann
Gerald
G
D000818:Animals; D004265:DNA Helicases / Q000037:antagonists & inhibitors*; D019915:DNA Primase / Q000037:antagonists & inhibitors*; D004279:DNA, Viral / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D018882:Heat Stress Disorders / Q000821:virology; D018259:Herpesvirus 1, Human; D016849:Keratitis, Herpetic / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011725:Pyridines / Q000627:therapeutic use*; D011817:Rabbits; D013449:Sulfonamides; D013666:Tears / Q000821:virology; D013844:Thiazoles / Q000627:therapeutic use*; D012668:Trigeminal Ganglion / Q000821:virology; D014764:Viral Proteins / Q000037:antagonists & inhibitors*; D017201:Virus Shedding / Q000187:drug effects
D004279:DNA, Viral; D004791:Enzyme Inhibitors; D011725:Pyridines; D013449:Sulfonamides; D013844:Thiazoles; D014764:Viral Proteins; C453221:pritelivir; D019915:DNA Primase; C062021:helicase-primase, Human herpesvirus 1; D004265:DNA Helicases