Effective Inhibition of Newly Emerged A/H7N9 Virus with Oligonucleotides Targeted to Conserved Regions of the Virus Genome

Newly emerged highly pathogenic A/H7N9 viruses with pandemic potential are effectively transmitted from birds to humans and require the development of novel antiviral drugs. For the first time, we studied the in vitro and in vivo antiviral activity against A/H7N9 of oligodeoxyribonucleotides (ODNs), which were delivered into the cells in the proposed TiO2-based nanocomposites (TiO2 similar to ODN). The highest inhibition of A/H7N9 in vitro (similar to 400-fold) and efficient, sequence-specific, and dose-dependent protection (up to 100%) of A/H7N9-infected mice was revealed when ODN was targeted to the conserved terminal 3 '-noncoding region of viral (-)RNA. After the treatment with ODN, the virus titer values in the lungs of mice decreased by several orders of magnitude. The TiO2 similar to ODN nanocomposite did not show toxicity in mice under the treatment conditions. The proposed approach for effective inhibition of the A/H7N9 can be tested against other viruses, for example, new emerging influenza viruses and coronaviruses with pandemic potential.

Automated summary

The study found that using TiO2-based nanocomposites similar to ODNs for ODN delivery can effectively inhibit A/H7N9 virus in vitro and in vivo. Targeting ODN to the conserved terminal 3'-noncoding region of viral RNA can provide efficient, sequence-specific, and dose-dependent protection, significantly reducing the virus titer in infected mice.