Evaluation of Various Analogues of Tilorone Hydrochloride Against Venezuelan Equine Encephalitis Virus in Mice

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Abstract
The antiviral activity of tilorone hydrochloride and three of its analogues (11,002, 11,567, and 11,877) was assessed by oral and intraperitoneal (i.p.) administration to Venezuelan equine encephalitis (VEE) virus-infected mice. Significant increases in the percentage of survival ( P < 0.01) were apparent after oral administration of tilorone and analogue 11,877 at dosages of 250 and 500 mg/kg. Neither tilorone nor 11,877 increased percentage of survival when dosages of 31.25 to 500 mg/kg were given by the i.p. route. Orally administered analogue 11,002 was effective against 100 mouse intracranial median lethal doses (MICLD 50 ) of VEE virus at doses at 250 to 1,000 mg/kg; doses of 31.25 to 250 mg/kg given i.p. were effective against 10 MICLD 50 . Oral dosages of 250 to 1,000 mg of analogue 11,567 per kg were active against 100 MICLD 50 of virus. By the i.p. route, 250 mg of 11,567 per kg protected mice against 1,000 MICLD 50 , and a dose of 125 mg/kg protected against 100 MICLD 50 . Oral treatment of VEE infection with analogue 11,567 24 h after subcutaneous inoculation of VEE virus resulted in no significant increase in the percentage of survivors. All survivors of these studies were susceptible to rechallenge 21 days after the first inoculation of virus.