
handle: 10451/28676
Ribavirin has been studied as an antiviral drug, but it is not yeat clear whether the compound is specifically antiviral in its mode of action or whether it inhibits virus replication as a result of its effect(s) the host cell. The effects on sellular metabolism are not well known and we have no notice any work about he effects of Ribavirin on the celiular ultrastructure, In preliminary results, treatment of CV1 culture cells win Rgjavirin in varying concentrations produced marked alterations in nucleoloar ultrastrustural organfzation — segregation, increase of the volume and extrusion of the fibrillar centers and in some celis the appearance of some nucleolar remmauts, consisting only of segregated amorphous and fibriliar comnonents, with or williout Lhe presence of severai íibriikr ijoduies in the intcrcromatin space. However, no alterations in the nitrastrusture of either the nucleus or cytoplasm were observed in cells examined in the same period of time. The incorporation of thymidine is CV1 cells in presence of Ribavirin (50 ug/ml or 100 g/ml) is delayed, atthough there is no difference, compared with the controls, after a period of nine hours after treatment. Similar ultrastructural lesions ara analysed in treated edis with other antimetabolites and in several cases, they are a consequense of the inibition of the synthesis of nucleolar pereursor RNA. The possible mechanism of RibaviriNa is the inibition of the enzime inosinc 5’-moophosphate (IMP) dehydrogenase, tHat bLocks the byosynThesis of nucleotides. The images observed lead to this interpretation and it is known tha these antimetabolites primarily affect nucleolar precursor biosynthesis.
Os autores agradecem a excelente colaboração técnica da Sr. D. Maria Lapão e dos Srs. João F. e Siva, José C. Afonso e Osvaldo Antunes.
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