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178 Effect of ribavirin on SSPE virus infection in hamsters
177 L •K. B ere zina, E .N. Pr eobra zhenskaya, D. K °Lvov • Antlviral activity of 1-methylascorbigen against bynyaviral infections (in experimental). D.I.Ivanovsky Research Institute of Virology Russian Academy of Medical Sciences,Institute of New Antibiotics. Prophylaxis of experimental arboviral infections in mice by 1-methylascorbigen which is a synthetic derivative of L-ascorbic acid is demonstrated.Mice infected by bunyawiruses (Rift valIey fever,Issyk-K~l fever, snow shoe hare laver and Crimean hemorragic fever) were protected by 1-methylascocbigen°The drug was administered subcutanconsly,per os and intramuscularey at the doses from 6,5 mg/kg to 50 m~L/kg. Random-bred albino mice were used in experiment.Doses and schedules of the compound were found when protection reached 100%.The antiviral effect of 1-methylascorbigen was some better them L-ascorbic acid.The antiviral effect is in agreement with prophylactic action of 1-methylascorbigen at several bacterial infections.Prophylactic activity of 1-methylascorbigen is probably based on its immunomodulatory properties.
178 Effect
of R i b a v i r i n
on SSPE Virus
Infection
in H a m s t e r s
M.Hosoya, Y.Honda, H.Suzuki, and S.Shigeta D e p a r t m e n t of M i c r o b i o l o g y and Pediatrics, F u k u s h i m a M e d i c a l College, F u k u s h i m a 960-12, Japan. Subacute sclerosing panencepharitis (SSPE) is a rare but p r o g r e s s i v e and fatal disorder of central nervous system. It results from a p e r s i s t e n t measles (SSPE) virus infection. In our s e a r c h for potential anti-SSPE drugs, we have e x a m i n e d a w i d e v a r i e t y of a n t i v i r a l c o m p o u n d s for t h e i r i n h i b i t o r y effects on the r e p l i c a t i o n of measles and SSPE virus strains in vitro, a n d f o u n d that s e v e r a l n u c l e o s i d e a n a l o g u e s , i n c l u d i n g ribavirin, are i n h i b i t o r y to the r e p l i c a t i o n of v a r i o u s SSPE v i r u s strains. In this study, we t e s t e d the a n t i v i r a l efficacy of ribavirin in the treatment of h a m s t e r s i n f e c t e d w i t h SSPE virus. R i b a v i r i n did not i m p r o v e the survival rate of infected hamsters when administered i n t r a p e r i t o n e a l l y at a dose of 50 m g / k g / d a y for ten days (maximum tolerated dose for h a m s t e r s ) . However, when a d m i n i s t e r e d intracranially, ribavirin i m p r o v e d the survival rate of infected hamsters in a dose dependent manner. The 50% e f f e c t i v e d o s e (required to i m p r o v e the s u r v i v a l rate of infected hamsters by 50%) was calculated to be 1.4 mg/kg/day. In particular, ribavirin showed m a r k e d a c t i v i t y at a dose of i0 m g / k g / d a y ; c o m p l e t e l y i m p r o v e d the s u r v i v a l r a t e a n d t o t a l l y inhibited the replication of SSPE virus in b r a i n s of i n f e c t e d hamsters. Ribavirin, therefore, s h o u l d be p u r s u e d for its p o t e n t i a l use in the treatment of p a t i e n t s w i t h SSPE by i n t r a t h e c a l or i n t r a v e n t r i c u l a r administration.
130
178 Effect
of R i b a v i r i n
on SSPE Virus
Infection
in H a m s t e r s
M.Hosoya, Y.Honda, H.Suzuki, and S.Shigeta D e p a r t m e n t of M i c r o b i o l o g y and Pediatrics, F u k u s h i m a M e d i c a l College, F u k u s h i m a 960-12, Japan. Subacute sclerosing panencepharitis (SSPE) is a rare but p r o g r e s s i v e and fatal disorder of central nervous system. It results from a p e r s i s t e n t measles (SSPE) virus infection. In our s e a r c h for potential anti-SSPE drugs, we have e x a m i n e d a w i d e v a r i e t y of a n t i v i r a l c o m p o u n d s for t h e i r i n h i b i t o r y effects on the r e p l i c a t i o n of measles and SSPE virus strains in vitro, a n d f o u n d that s e v e r a l n u c l e o s i d e a n a l o g u e s , i n c l u d i n g ribavirin, are i n h i b i t o r y to the r e p l i c a t i o n of v a r i o u s SSPE v i r u s strains. In this study, we t e s t e d the a n t i v i r a l efficacy of ribavirin in the treatment of h a m s t e r s i n f e c t e d w i t h SSPE virus. R i b a v i r i n did not i m p r o v e the survival rate of infected hamsters when administered i n t r a p e r i t o n e a l l y at a dose of 50 m g / k g / d a y for ten days (maximum tolerated dose for h a m s t e r s ) . However, when a d m i n i s t e r e d intracranially, ribavirin i m p r o v e d the survival rate of infected hamsters in a dose dependent manner. The 50% e f f e c t i v e d o s e (required to i m p r o v e the s u r v i v a l rate of infected hamsters by 50%) was calculated to be 1.4 mg/kg/day. In particular, ribavirin showed m a r k e d a c t i v i t y at a dose of i0 m g / k g / d a y ; c o m p l e t e l y i m p r o v e d the s u r v i v a l r a t e a n d t o t a l l y inhibited the replication of SSPE virus in b r a i n s of i n f e c t e d hamsters. Ribavirin, therefore, s h o u l d be p u r s u e d for its p o t e n t i a l use in the treatment of p a t i e n t s w i t h SSPE by i n t r a t h e c a l or i n t r a v e n t r i c u l a r administration.
130