title: Antiviral efficacy of VP14637 against respiratory syncytial virus in vitro and in cotton rats following delivery by small droplet aerosol.
abstract: VP14637, the lead compound in a series of substituted bis-tetrazole-benzhydrylphenols developed by ViroPharma Incorporated, was evaluated for antiviral efficacy against respiratory syncytial virus (RSV) in vitro in cell culture and in vivo in cotton rats. A selective index of >3000 (> or =2000 times greater than that observed for ribavirin) was determined in the in vitro studies for this compound against both RSV A and B subtypes. In cotton rats, animals given as little as 126 microg drug/kg by small droplet aerosol in divided doses starting 1 day after experimental virus infection with either a RSV A or B subtype consistently had significantly lower mean pulmonary RSV titers and reduced histopathological findings than mock-treated animals or cotton rats given placebo (vehicle-treated animals). No cotton rat treated with aerosols of VP14637 during these studies manifested any evident untoward responses. Thus, VP14637 exhibited good selective antiviral efficacy both in vitro and in vivo.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. pwyde@bcm.tmc.edu
authors.forename: Philip R
authors.initials: PR
authors.lastname: Wyde
authors.forename: Sylvie
authors.initials: S
authors.lastname: Laquerre
authors.forename: Srikrishna N
authors.initials: SN
authors.lastname: Chetty
authors.forename: Brian E
authors.initials: BE
authors.lastname: Gilbert
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Nitz
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Pevear
mesh_terms: D000336:Aerosols; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D010636:Phenols / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D016205:Sigmodontinae; D013777:Tetrazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000336:Aerosols; D000998:Antiviral Agents; D001559:Benzhydryl Compounds; D010636:Phenols; D013777:Tetrazoles