Inhibition of influenza virus replication by phosphorothioate oligodeoxynucleotides

J. M.E. Leiter, S. Agrawal, P. Palese, P. C. Zamecnik

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Oligodeoxynucleotides (ODNs) were synthesized and tested for their antiviral activity against influenza viruses. ODNs corresponded to the polymerase PB1 gene of either influenza A/WSN/33 virus or influenza C/JJ/50 virus. All compounds were 20 nucleotides long, including control ODNs containing mismatches. The phosphodiester ODNs (O-ODNs) failed to inhibit replication of influenza A and influenza C viruses at concentrations up to 80 μM, possibly due to intracellular nuclease digestion of the unmodified oligomers. By contrast, the phosphorothioate derivatives (S-ODNs) were found to inhibit replication of both influenza A and influenza C virus. The antiviral effect of S-ODNs against influenza A virus was found at concentrations as low as 1.25 μM and was present with mismatched oligomers. In the case of influenza C virus, the S-ODN complementary to the 3' end of the viral RNA of the PB1 gene revealed a sequence-specific antiviral activity at a concentration of 20 μM. (At the same concentration, S-ODNs with one or three mismatches showed little or no antiviral activity.) Reduction in plaque number reached six logarithms when this sequence-specific S-ODN was used at a concentration of 80 μM.

Original languageEnglish
Pages (from-to)3430-3434
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - 1990


  • RNa virus
  • antisense DNA
  • antiviral


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