Partial inhibition of yellow fever virus replication in vitro with different phosphorothioate...

Phosphorothioate oligodeoxyribonucleotides targeted to different regions of the viral genome were synthesized and used in two kinds of experiments testing their activity against yellow fever virus (YFV) replication in cultured cells. We found that oligonucleotides complementary to the 3'-end or to the coding region of the viral RNA were regularly active in plaque reduction assay, although with inconstant efficiency. Oligonucleotides targeted to the 5'-end or to the initiation codon region exhibited lesser activity. Homologous oligonucleotides targeted to dengue virus RNA had no detectable inhibitory activity against dengue virus replication. However, in YFV production reduction assay, a non-specific inhibitory activity of a random oligonucleotide was observed. Taken as a whole, our results indicate that flaviviruses present detectable but heterogeneous sensitivity to phosphorothioate inhibition. Possible explanations are discussed.