IN VITRO EVALUATION OF THE ANTIVIRAL ACTIVITY OF THE ASPIRIN / DIETHYL ETHER (ADE) MIXTURE FOR HERPES ZOSTER AND POST-HERPETIC NEURALGIA

Aim of investigation. The efficacy of topical aspirin/diethyl ether mixture in the treatment of acute herpetic neuralgia and post-herpetic neuralgia had been established in two, previous open-label and placebo- controlled studies (De Benedittis et al., Pain 48: 383-390 , 1992; De Benedittis & Lorenzetti,Abstracts, 7th World Congress on Pain , Paris, p. 186 , IASP Publications, Seattle,1993). Moreover, a striking reduction of the percentage of acute herpetic neuralgia patients developing post-herpetic neuralgia had been observed in the treated groups as compared with the disease natural history reported in the literature. Since this action could be assumed as an indirect, objective indicator of treatment efficacy in controlling the severity of Herpes Zoster, the aim of the present study was to evaluate the in vitro activity of the ADE mixture on both viral particles and replicative cycle of varicella-zoster virus (VZV) and herpes simplex virus type l(HSV1) as the Herpesviridae prototype virus. Method. Suspensions of HSV1 were incubated alternatively with Aspirin 400 mM, diethyl ether and the mixture (1:1, v/v) of the two; the reduction of the viral titer was assessed by the plaque reduction assay. The activity on viral replication was checked on human fetal fibroblasts (MRCS) infected with VZV and on african green monkey kidney cells (VERO) infected with HSV1, and the 50% inhibiting dose (ID50) was calculated. Results. A 100% reduction of the suspensions titer was obtained both by the mixture and the ether; no effect was observed following the incubation with aspirin alone. An inhibition of the replicative cycle by aspirin was observed. The ID50 resulted in the range (1-3 mM) of the plasma concentrations attained in the clinical treatment of inflammation. Conclusions. Preliminary data indicate an antiviral activity of aspirin which is exerted at a replicative level but not on the viral particle. The antiviral effect might be due to inhibition by aspirin and Na salicylate of the transcription factor NF-kB (Kopp & Gosh, Science, 128: 432-435, 1994). Further studies aimed at assessing the aspirin concentrations attained by topical use and the viral replication stage of the inhibition are irrprugress-.--