Abstract: The present invention relates to novel ribonucleotide oligonucleotides (RNOs) that are specifically designed to inhibit viral replication. The RNOs are capable of binding to both the negative and positive strands of influenza RNA segments, thereby inhibiting the virus' ability to produce various viral components, thus inhibiting viral propagation, and effectively killing the virus at the intracellular sites of infection in the respiratory tract. The RNOs provided may act independently, or in combination to optimize their antiviral activity. In addition, the RNOs provided may be formulated in liposomes, which facilitate their therapeutic delivery to intracellular sites of infection, and additionally increase antiviral efficacies.