Toxicity and antiviral activity of LY253963 against respiratory syncytial and parainfluenza type 3 viruses in tissue culture and in cotton rats.
LY253963, the sodium salt of 1,3,4-thiadiazol-2-ylcyanamide, was evaluated in tissue culture and in cotton rats for toxicity and antiviral efficacy against respiratory syncytial (RSV) and parainfluenza type 3 (PIV3) viruses. The selective index (ratio of the median toxic dose: median efficacious dose) of LY253963 in HEp2 tissue culture cells was greater than 100 against both RSV and PIV3. When given intraperitoneally to cotton rats, the minimum protective dose of LY253963 against both of these viruses was between 1 and 3 mg/kg/day. In contrast, doses of LY253963 as high as 30 mg/kg/day, administered orally after experimental inoculation of virus, did not significantly reduce pulmonary virus titers in treated animals compared to control animals given placebo. No toxic effects were noted in cotton rats, even in those given 20 mg/kg/day for eight consecutive days.
Wyde
P R
PR
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030.
Ambrose
M W
MW
Meyer
H L
HL
Gilbert
B E
BE
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009570:Nitriles / Q000494:pharmacology*; D018184:Paramyxoviridae Infections / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D018108:Respirovirus / Q000187:drug effects*; D010253:Respirovirus Infections / Q000188:drug therapy* / Q000473:pathology; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology; D013830:Thiadiazoles / Q000494:pharmacology*
D000998:Antiviral Agents; D009570:Nitriles; D013830:Thiadiazoles; C067593:1,3,4-thiadiazol-2-ylcyanamide; D012254:Ribavirin