Failure of high doses of potentially antiviral agents to prevent death in virus-infected mice.

The influence of increasing doses of various potentially antiviral agents on Mengo virus-and Sindbis virus-infected mice was assessed determining death rates and histologic lesions. All drugs given in abundance showed dose-dependent decrease of antiviral activity following the maximum protective effects in either animal model. From the toxicological point of view the antiviral agents in question could be classified into two groups. High doses of tilorone hydrochloride or 10-carboxymethyl-9-acridanone produced toxic effects in both uninfected and virus-infected animals. In contrast, high doses of quercetin, double-stranded ribonucleic acid (dsRNA), 1-ethylisatin-S-n-butylisothiosemicarbazone or Norakin induced no obvious drug-mediated histologic alterations either in uninfected or in virus-infected individuals, but exerted a decreased protection in virus-infected animals. It is suggested that high doses of the compounds of second group adversely affect early host defence in both Mengo virus and Sindbis virus-infected mice.