The in vivo antiviral effect of CL246,738 is mediated by the independent induction of interferon-alpha and interferon-beta.
An interferon (IFN) inducer and immunomodulator, CL246,738 [3,6-bis(2-piperidinoethoxy)acridine trihydrochloride], protected mice from lethal infection with Semliki Forest (SFV) and Banzi (BZV) viruses. A single oral dose of CL246,738 (5-150 mg/kg) administered 24 h before intraperitoneal challenge with SFV or BZV fully protected mice from lethal infection. Dose-dependent levels of circulating IFN peaked at 24 h in the serum and peritoneal fluid of CL246,738-treated mice. The circulating IFN of CL246,738-treated mice consisted of IFN-alpha and was produced by spleen cells. Peritoneal exudate cells (PEC) obtained from CL246,738-treated mice produced IFN-beta. Treatment in vivo with anti-IFN-alpha/beta and anti-IFN-beta reversed the protective effect of CL246,738 against lethal SFV encephalitis.
Sarzotti
M
M
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
Coppenhaver
D H
DH
Singh
I P
IP
Poast
J
J
Baron
S
S
D000166:Acridines / Q000494:pharmacology*; D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000517:prevention & control; D005260:Female; D005416:Flavivirus / Q000187:drug effects; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000096:biosynthesis*; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D012672:Semliki forest virus / Q000187:drug effects; D014036:Togaviridae Infections / Q000517:prevention & control*
D000166:Acridines; D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D007369:Interferon Inducers; D007370:Interferon Type I; C045570:3,6-bis(2-piperidinoethoxy)acridine trihydrochloride