Efficacy of glycoprotein inhibitors alone and in combination with trifluridine in the treatment of murine herpetic keratitis.
The present study examined the anti-herpetic effect of the glycoprotein inhibitors, hydroxynorvaline and 2-deoxyglucose, alone and in combination with trifluridine on murine ocular herpes. Following ocular inoculation with a large dose of HSV-1 RE strain (10(6) pfu), ICR mice were treated during the acute infection with different therapeutic regimens, and their efficacy was evaluated by ocular virus titers, clinical grading of blepharo-conjunctivitis and histological evaluation of stromal keratitis and iridocyclitis. The results following a large dose HSV-1 inoculum demonstrated that trifluridine was the best single therapeutic agent. Hydroxynorvaline and 2-deoxyglucose had no effect at all. Combination therapy of the glycoprotein inhibitors with trifluridine was no better than trifluridine alone. The mouse HSV-1 keratitis model proved to be an effective, economical alternative to the rabbit model for the evaluation of new antiviral agents.
Gordon
Y J
YJ
Cheng
K P
KP
Araullo-Cruz
T
T
Romanowski
E
E
Johnson
B J
BJ
Blough
H A
HA
D000818:Animals; D003231:Conjunctivitis / Q000473:pathology; D003837:Deoxy Sugars / Q000627:therapeutic use*; D003847:Deoxyglucose / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005123:Eye / Q000473:pathology; D007635:Keratitis, Dendritic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013912:Threonine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013936:Thymidine / Q000031:analogs & derivatives*; D014271:Trifluridine / Q000627:therapeutic use*
D003837:Deoxy Sugars; C010994:3-hydroxynorvaline; D013912:Threonine; D003847:Deoxyglucose; D014271:Trifluridine; D013936:Thymidine