Oligonucleotides-poly(L-lysine) conjugates exhibit specific antiviral activity against VSV at low concentrations through mechanisms that likely extend beyond translational inhibition.
Synthetic oligonucleotides (oligomers) complementary to vesicular stomatitis virus (VSV) N protein mRNA have specific antiviral properties at concentrations lower than 1 microM when they are covalently linked to poly(L-lysine) (PLL). Since it is generally postulated that antisense oligomers act at the translational level, oligomers with potential targets on VSV viral mRNA and/or genomic RNA have been tested here. In vitro translation experiments in reticulocyte lysates, in vitro transcription experiments with permeabilized viruses, measurement of viral RNA transcription and accumulation in VSV infected cells, and antiviral experiments demonstrate in our model that antisense oligomers probably also act at other levels. Difficulties in the choice of the most effective antisense oligomer targets are also discussed.
Degols et al. (Sun,) studied this question.