Enhanced efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine in combination with beta-interferon against herpes simplex virus type 2 in mice

Abstract

The acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) and natural mouse interferon beta (MuIFN-P) were evaluated for their efficacy alone and in combination against herpes simplex virus type 2 systemic infections in mice. Intraperitoneally infected animals were treated once a day with the drugs at various concentrations for 5 days starting 24 h after inoculation. DHPG was injected subcutaneously at doses of 0.7 to 6 mg/kg. MuIFN-,B was given intraperitoneally at doses ranging from 3 x 103 to 3 x 104 IU per mouse. For DHPG alone, the effective dose at which 50% of the mice survived (ED50) was >6 mg/kg.However, when given in combination with an ineffective dose of MuIFN-_B (104 IU per mouse), the ED50 for DHPG was 0.8 mg/kg. In addition, at the highest dose tested, MuIFN-P alone had no protective activity against herpes simplex virus type 2 (ED50, >3 x 104 IU per mouse). However, when given in combination with a marginally effective dose of DHPG (2 mg/kg), the ED50 for MuIFN-, was <3 x 103 IU per mouse.

Enhanced efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine in combination with alpha-interferon against herpes simplex virus type 2 in mice

“…The present in vivo results, which demonstrate a 10-fold enhancement of anti-HSV-2 activity with the combination of DHPG and rHuIFN-a-AD, are similar to previous in vivo results with DHPG and MuIFN-P (3). Because the same specific antiviral activity of IFN (104 IU/mouse) was found to reduce the ED50 of DHPG -10-fold, natural MuIFN-P and rHuIFN-a appear to be equally active and may have similar modes of action against HSV.…”

“…DHPG (Syntex Research) and rHuIFN-ox-AD (HoffmannLa Roche, Inc.) were prepared as described previously (3). The specific activity of the rHuIFN-(x-AD was 108 international reference units (IU) per mg as determined by titration * Corresponding author.…”

Inhibitory effects of selected antiviral compounds on newly isolated clinical varicella-zoster virus strains.

“…Furthermore, it has been demonstrated that the combinations of interferon and DHPG have synergistic antiviral effects on HSV replication in vitro and in vivo Fraser-Smith et al 1984). Our preliminary investigations (data not shown) indicate that DHPG and interferon may also have synergistic inhibitory effect on VZV replication in vitro.…”

Interferon in the prevention of genital herpes recurrence

“…While it is possible that with larger numbers a statistically significant effect of interferon may be demonstrable, in view of its toxicity it appears unlikely that this type of interferon (alpha2b), dosage schedule, or route of administration will have a therapeutic or suppressive role in genital herpes. However, we are using topical routes of administration to reduce toxicity and combining interferon with other antiviral agents which show in vitro synergy with interferon (5,8) to attempt to demonstrate a clinically useful effect in patients with genital herpes.…”