The helicase primase inhibitor, BAY 57-1293 shows potent therapeutic antiviral activity superior to famciclovir in BALB/c mice infected with herpes simplex virus type 1.
BAY 57-1293 represents a new class of potent inhibitors of herpes simplex virus (HSV) that target the virus helicase primase complex. The present study was conducted using the zosteriform infection model in BALB/c mice. The helicase primase inhibitor, BAY 57-1293 was shown to be highly efficacious in this model. The beneficial effects of therapy were obtained rapidly (within 2 days) although the onset of treatment was delayed for 1 day after virus inoculation. The compound given orally, or intraperitoneally once per day at a dose of 15 mg/kg for 4 successive days was equally effective or superior to a much higher dose of famciclovir (1mg/ml, i.e. approximately 140-200mg/kg/day) given in the drinking water for 7 consecutive days, which, in our hands, is the most effective method for administering famciclovir to mice. In contrast to the vehicle-treated infected mice, all mice that received antiviral therapy looked normal and active with no mortality, no detectable loss of weight and no marked change in ear thickness. BAY 57-1293 and famciclovir reduced the virus titers in the skin to below the level of detection by days 3 and 7 post infection, respectively. In both BAY 57-1293 and famciclovir-treated mice, infectious virus titers in the ear pinna and brainstem remained below the level of detection. Consistent with these findings, BAY 57-1293 also showed a potent antiviral effect in an experiment involving a small number of severely immunocompromised athymic-nude BALB/c mice.
Biswas
Subhajit
S
Centre for Veterinary Science, Cambridge University Veterinary School, Madingley Road, Cambridge, CB3 0ES, UK.
Jennens
Lyn
L
Field
Hugh J
HJ
D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001933:Brain Stem / Q000821:virology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004423:Ear / Q000821:virology; D000077595:Famciclovir; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000821:virology; D013449:Sulfonamides; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000998:Antiviral Agents; D011725:Pyridines; D013449:Sulfonamides; D013844:Thiazoles; C453221:pritelivir; D015075:2-Aminopurine; D000077595:Famciclovir