In vivo antiviral activity of ribavirin/alpha-cyclodextrin complex: evaluation on experimental measles virus encephalitis in mice.
Intracranial injection of the rodent adapted CAM/RB strain of measles virus (MV) induces encephalitis in CBA/ca mice. It has already been shown that cyclodextrins can be used as carriers to increase the antiviral activity of ribavirin (RBV) against MV in cellular model. In this study, the antiviral activity of a RBV/alpha-cyclodextrin complex has been evaluated in vivo using the above model. CBA/ca mice were treated by intraperitoneal injection of free ribavirin (40 mg/kg) or a RBV/alpha-cyclodextrin complex (molar ratio 1:3). After 21 days, intracerebral injection of CAM/RB resulted in 100% mortality in the mock group. In contrast, mortality rates of 80% and 40%, respectively, were observed in RBV and RBV/alpha-CD-treated mice (p<0.05 and p=0.06 for distilled water and RBV, respectively). The viral load of MV in the mouse brain was monitored daily by real-time PCR until day 6 after infection, to compare virus production in treated and non-treated mice. This data shows that RBV complexation with alpha-cyclodextrin can increase the antiviral activity of ribavirin in a measles virus encephalitis model in mice.
Jeulin
H
H
GEVSM-SRSMC-UMR 7565 CNRS/Nancy Université, Faculté de Médecine, Laboratoire de Virologie, 9 Avenue Forêt de Haye, B.P. 184, 54505 Vandoeuvre-lès-Nancy, France. helene.jeulin@pharma.uhp-nancy.fr
Grancher
N
N
Kedzierewicz
F
F
Finance
C
C
Le Faou
A E
AE
Venard
V
V
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D018792:Encephalitis, Viral / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D005260:Female; D008297:Male; D008457:Measles / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D008459:Measles virus; D051379:Mice; D008808:Mice, Inbred CBA; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012015:Reference Standards; D012254:Ribavirin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016019:Survival Analysis; D019562:Viral Load; D047391:alpha-Cyclodextrins / Q000737:chemistry*
D000998:Antiviral Agents; D018076:DNA, Complementary; D004279:DNA, Viral; D047391:alpha-Cyclodextrins; D012254:Ribavirin; D012313:RNA