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Journal of Antimicrobial Chemotherapy (1996) 37, 303-313
© 1996 The British Society for Antimicrobial Chemotherapy

research-article

Activity of penciclovir in antiviral assays against herpes simplex virus

Teresa H. Bacon*, Barbara A. Howard, Lindsay C. Spender{ddagger} and Malcolm R. Boyd

SmithKline Beecham Pharmaceuticals, Brockham Park Betchworth, Surrey RH3 7AJ, UK

Received 24 March 1995; returned 21 June 1995; accepted 10 September 1995

*Correspondence to: Teresa H. Bacon, SmithKline, Beecham Pharmaceuticals, New Frontiers Science Park South, Third Avenue, Hariow, Essex CMI9 5AW, UK

The effect of penciclovir and acyclovir on the replication of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) strains was determined in MRC-5 cells infected with 0.01 pfu/cell and exposed to the drugs for 72 h to allow multiple cycles of replication. Penciclovir was significantly more active than acyclovir against three strains of HSV-1 and three strains of HSV-2 at 1 mg/L (P=0.009), 3 mg/L (P<0.001) and 10 mg/L (P=0.001). Further comparisons between the compounds were made in MRC-5 cells infected with HSV-1 strain SCI6 using four different antiviral assays namely, the 24 h virus yield reduction assay, plaque reduction assay, viral antigen inhibition assay, and a viral DNA inhibition assay, to determine the relative merits of each. Penciclovir and acyclovir shared similar activities in the plaque reduction assay (with 50% effective concentrations, EC50, being 0.8 and 0.6 mg/L, respectively) and in the viral antigen inhibition assay (EC50s, 0.6 and 0.7 mg/L, respectively). The EC50 of penciclovir in the 24 h viral DNA inhibition assay was 0.01 mg/L compared with 0.06 mg/L of acyclovir. In the 24 h virus yield reduction assay in which MRC-5 cells were infected with 0.3 pfu/cell, penciclovir was more active than acyclovir with 99% effective concentrations of 0.6 mg/L and 1.1 mg/L, respectively. The activity of penciclovir in the 24 h virus yield reduction and antigen inhibition assays was inversely related to the multiplicity of infection, whereas this had considerably less effect on the inhibition of viral DNA synthesis. These results suggest that famciclovir, which is the oral form of penciclovir, will be at least as effective as acyclovir in treating infections caused by HSV-1 and HSV-2.


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